Immunostimulating based on bacterial antigens. Immunomodulators. Interferons and their inducers

Classification of immunoactive agents:

A: Immunostimulants:

I IS of bacterial origin

1. Vaccines (BCG, CP)

2. Microbial lipopolysaccharides of Gr-negative bacteria

riy (prodigiosan, pyrogenal, etc.)

3. Low molecular weight immunocorrectors

II Preparations of animal origin

1. Preparations of thymus, bone marrow and their analogues (ti

raspberries, taktivin, thymogen, vilozen, myelopid, etc.)

2. Interferons (alpha, beta, gamma)

3. Interleukins (IL-2)

III Herbal preparations

1. Yeast polysaccharides (zymosan, dextrans, glucans)

IV Synthetic immunoactive agents

1. Derivatives of pyrimidines (methyluracil, pentoxyl,

orotic acid, diucifon)

2. Imidazole derivatives (levamisole, dibazol)

3. Trace elements (Compounds Zn, Cu, etc.)

V Regulatory peptides (tuftsin, dolargin)

VI Other immunoactive agents (vitamins, adaptogens)

B: Immunosuppressants

I Glucocorticoids

II Cytostatics

1. Antimetabolites

a) purine antagonists;

b) pyrimidine antagonists;

c) amino acid antagonists;

d) folic acid antagonists.

2. Alkylating agents

3. Antibiotics

4. Alkaloids

5. Enzymes and enzyme inhibitors

Along with the above means, physical and biological methods of influencing immunity are distinguished:

1. Ionizing radiation

2. Plasmapheresis

3. Drainage of the thoracic lymphatic duct

4. Anti-lymphocyte serum

5: Monoclonal antibodies

The pathology of immune processes is very common. According to far from complete data, the participation, to one degree or another, of the immune system in the pathogenesis of diseases of internal organs has been proven for 25% of patients in therapeutic polyclinics of the country.

The rapid development of experimental and clinical immunology, the deepening of knowledge about the pathogenesis of immune disorders in various diseases, determined the need to develop a method of immunocorrection, the development of experimental and clinical immunopharmacology. Thus, a special science was formed - immunopharmacology, a new medical discipline, the main task of which is the development of pharmacological regulation of impaired functions of the immune system using immunoactive (immunotropic) agents. The action of these agents is aimed at normalizing the functions of cells involved in the immune response. Here, modulation of two conditions encountered in the clinic, namely immunosuppression or immunostimulation, is possible, which significantly depends on the characteristics of the patient's immune response. This raises the problem of optimal immunotherapy that modulates immunity in the clinically necessary direction. Thus, the main goal of immunotherapy is a directed impact on the ability of the patient's body to an immune response.

Based on this, and also taking into account the fact that in the clinical practice of a doctor it may be necessary to conduct both immunosuppression and immunostimulation, all immunoactive agents are divided into immunosuppressants and immunostimulants.

As a rule, drugs are called immunostimulants, which integrally, in general, increase the humoral and cellular immune response.

Due to the complexity of choosing a specific drug, regimen and duration of therapy, it is necessary to dwell in more detail on the characteristics and clinical use of the most promising immunostimulating drugs that have been tested in the clinic.

The need to stimulate the immune system arises with the development of secondary immunodeficiencies, that is, with a decrease in the function of effector cells of the immune system caused by a tumor process, infectious, rheumatic, bronchopulmonary diseases, pyelonephritis. which ultimately leads to chronicity of the disease, the development of opportunistic infection, resistance to antibiotic treatment.

The main feature of immunostimulants is that their action is not aimed at the pathological focus or pathogen, but at non-specific stimulation of monocyte populations (macrophages, T- and B-lymphocytes and their subpopulations).

By type of exposure, there are two ways to enhance the immune response:

1. Active

2. Passive

The active method, like the passive one, can be specific and non-specific.

Active specific method of enhancing the immune response includes the use of methods for optimizing the scheme of administration of the antigen and antigenic modification.

An active non-specific way to enhance the immune response includes, in turn, the use of adjuvants (Freund, BCG, etc.), as well as chemical and other drugs.

Passive specific method of enhancing the immune response involves the use of specific antibodies, including monoclonal antibodies.

Passive non-specific method includes the introduction of donor plasma gamma globulin, bone marrow transplantation, the use of allogeneic drugs (thymic factors, lymphokines).

Since there are certain limitations in the clinical setting, the main approach to immunocorrection is non-specific therapy.

Currently, the number of immunostimulating agents used in the clinic is quite large. All existing immunoactive drugs are used as pathogenetic therapy drugs that can influence various parts of the immune response, and therefore these drugs can be considered as homeostatic agents.

According to the chemical structure, method of preparation, mechanism of action, these agents represent a heterogeneous group, therefore there is no single classification. The classification of immunostimulants by origin seems to be the most convenient:

1. IS of bacterial origin

2. IP of animal origin

3. IP of vegetable origin

4. Synthetic ICs of various chemical structures

5. Regulatory peptides

6. Other immunoactive agents

Immunostimulators of bacterial origin include vaccines, lipopolysaccharides of Gram-negative bacteria, low molecular weight immunocorrectors.

In addition to inducing a specific immune response, all vaccines cause immunostimulatory effects to varying degrees. The best studied vaccines are BCG (which contains the non-pathogenic Calmette-Guérin bacillus) and CP (Corynobacterium parvum), pseudodiphtheroid bacteria. With their introduction, the number of macrophages in tissues increases, their chemotaxis and phagocytosis increase, monoclonal

nal activation of B-lymphocytes, the activity of natural killer cells increases.

In clinical practice, vackins are used mainly in oncology, where the main indications for their use are the prevention of relapses and metastases after combined treatment of a tumor carrier. Usually, the start of such therapy should be a week ahead of other treatments. For the introduction of BCG, for example, you can use the following scheme: 7 days before surgery, 14 days after it, and then 2 times a month for two years.

Side effects include many local and systemic complications:

Ulceration at the injection site;

Prolonged persistence of mycobacteria at the injection site;

Regional lymphadenopathy;

Heartache;

Collapse;

Leukothrombocytopenia;

DIC syndrome;

Hepatitis;

With repeated injections of the vaccine into the tumor, anaphylactic reactions may develop.

The most serious danger in the use of vaccines for the treatment of patients with neoplasms is the phenomenon of immunological enhancement of tumor growth.

Due to these complications, their high frequency, vaccines as immunostimulants are becoming less and less used.

Bacterial (microbial) lipopolysaccharides

The frequency of use of bacterial lipopolysaccharides in the clinic is rapidly increasing. LPS of gram-negative bacteria are especially intensively used. LPS are structural components of the bacterial wall. The most commonly used prodigiosan is derived from Bac. prodigiosum and pyrogenal obtained from Pseudomonas auginosa. Both drugs increase resistance to infection, which is achieved primarily by stimulating nonspecific defense factors. The drugs also increase the number of leukocytes and macrophages, enhance their phagocytic activity, the activity of lysosomal enzymes, and the production of interleukin-1. This is probably why LPS are polyclonal stimulators of B-lymphocytes and inducers of interferons, and in the absence of the latter, they can be used as their inducers.

Prodigiosan (Sol. Prodigiosanum; 1 ml of 0.005% solution) is administered intramuscularly. Usually a single dose for adults is 0.5-0.6 ml, for children 0.2-0.4 ml. Enter with an interval of 4-7 days. The course of treatment is 3-6 injections.

Pyrogenal (Pyrogenalum in amp. 1 ml (100; 250; 500; 1000 MPI minimum pyrogenic doses)) The dose of the drug is selected individually for each patient. Enter intramuscularly once a day (every other day). The initial dose is 25-50 MPD, while the body temperature rises to 37.5-38 degrees. Either 50 MTD are administered, daily increasing the dose by 50 MTD, bringing it to 400-500 MTD, then gradually reduce it by 50 MTD. The course of treatment is up to 10-30 injections, only 2-3 courses with a break of at least 2-3 months.

Indications for use:

For persistent pneumonia

Some variants of pulmonary tuberculosis,

chronic osteomyelitis,

To reduce the severity of allergic reactions

(with atopic bronchial asthma),

To reduce the incidence of anemia in patients with chronic

Kim tonsillitis (with prophylactic endonasal administration

Pyrogenal is also shown:

To stimulate recovery processes after

injuries and diseases of the central nervous system,

For resorption of scars, adhesions, after burns, injuries, spa

bowel disease,

With psoriasis, epidymitis, prostatitis,

For some stubborn dermatitis (urticaria),

In chronic inflammatory diseases of the female polo

external organs (long-term sluggish inflammation of the appendages),

As an additional tool in the complex therapy of syphilis.

Side effects include:

Leukopenia

Exacerbation of chronic bowel disease, diarrhea.

Prodigiosan is contraindicated in myocardial infarction, central disorders: chills, headache, fever, joint and lower back pain.

Low molecular weight immunocorrectors

This is a fundamentally new class of immunostimulating drugs of bacterial origin. These are peptides with a small molecular weight. Many drugs are known: bestatin, amastatin, ferfenecin, muramyl dipeptide, biostim, etc. Many of them are at the stage of clinical trials.

The most studied is bestatin, which has shown itself especially well in the treatment of patients with rheumatoid arthritis.

In France, in 1975, a low molecular weight peptide, muramyl dipeptide (MDP), was obtained, which is the minimum structural component of the cell wall of mycobacteria (a combination of peptide and polysaccharide).

The clinic now widely uses biostim - a very active

ny glycoprotein isolated from Klebsiellae pneumoniae. It is a polyclonal B-lymphocyte activator that induces the production of interleukin-1 by macrophages, activates the production of nucleic acids, increases macrophage cytotoxicity, and increases the activity of cellular nonspecific defense factors.

It is indicated for patients with broncho-pulmonary pathology. The immunostimulating effect of Biostim is achieved by administering a dose of 1-2 mg/day. The action is stable, duration - 3 months after the cessation of the drug administration.

There are practically no side effects.

Speaking about immunostimulants of bacterial, but not of corpuscular origin in general, three main stages should be distinguished, but in fact three generations of immunostimulating agents of bacterial origin:

Creation of purified bacterial lysates, they have the specific properties of vaccines and are non-specific immunostimulants. The best representative of this generation is Bronchomunalum (capsules 0.007; 0.0035), a lysate of eight of the most pathogenic bacteria. It has a stimulating effect on humoral and cellular immunity, increases the number of macrophages in the peritoneal fluid, as well as the number of lymphocytes and antibodies. The drug is used as an adjuvant in the treatment of patients with infectious diseases of the respiratory tract. When taking bronchomunal, side effects in the form of dyspepsia and allergic reactions are possible. The main disadvantage of this generation of immunostimulating agents of bacterial origin is weak and unstable activity.

Creation of fractions of cell membranes of bacteria that have a pronounced immunostimulating effect, but do not have the properties of vaccines, that is, do not cause the formation of specific antibodies.

The combination of bacterial ribosomes and cell wall fractions represents a new generation of drugs. A typical representative of it is Ribomunal (Ribomunalum; in tab. 0, 00025 and aerosol 10 ml) - a preparation containing ribosomes of 4 main pathogens of upper respiratory tract infections (Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes A, Haemophillus influenzae) and Klebsiella membrane proteoglycans pneumoniae. It is used as a vaccine for the prevention of recurrent infections of the respiratory tract and ENT organs. The effect is achieved by increasing the activity of natural killers, B-lymphocytes, increasing the level of IL-1, IL-6, alpha-interferon, secretory immunoglobulin A, as well as by increasing the activity of B-lymphocytes and the formation of specific serum antibodies to 4 ribosomal antigens. There is a specific regimen for taking the drug: 3 tablets in the morning for 4 days a week for 3 weeks, and then for

4 days a month for 5 months; subcutaneously: administered 1 time per week for 5 weeks, and then 1 time per month for 5 months.

The drug reduces the number of exacerbations, the duration of episodes of infections, the frequency of antibiotic prescription (by 70%) and causes an increase in the humoral response.

The greatest effectiveness of the drug is manifested when it is administered parenterally.

With subcutaneous administration, local reactions are possible, and with inhalation - transient rhinitis.

Immunoactive drugs of animal origin

This group is the most widely and frequently used. Of greatest interest are:

1. Preparations of thymus, bone marrow and their analogues;

2. A new group of B-lymphocyte stimulators:

Interferons;

Interleukins.

Thymus preparations

Every year the number of compounds obtained from the thymus and differing in chemical composition and biological properties increases. Their action is such that, as a result, the maturation of precursors (precursors) of T-lymphocytes is induced, differentiation and proliferation of mature T-cells, expression of receptors on them is ensured, and antitumor resistance is also enhanced and repair processes are stimulated.

The following thymus preparations are most often used in the clinic:

Timalin;

Thymogen;

Taktivin;

Vilozen;

Timoptin.

Timalin is a complex of polypeptide fractions isolated from the thymus of cattle. Available in vials as a lyophilized powder.

It is used as an immunostimulant for:

Diseases accompanied by a decrease in cellular immunity

In acute and chronic purulent processes and inflammatory

diseases;

With burn disease;

With trophic ulcers;

With suppression of immunity and hematopoietic function after lu

chemotherapy or chemotherapy in cancer patients.

The preparation is administered intramuscularly at a dose of 10-30 mg daily for

5-20 days. If necessary, the course is repeated after 2-3 months.

A similar drug is timoptin (unlike thymalin, it does not act on B cells).

Taktivin - also has a heterogeneous composition, that is, it consists of several thermostable fractions. It is more active than thymalin. Has the following effect:

Restores the number of T-lymphocytes in patients with their low

Increases the activity of natural killers, as well as killer

ny activity of lymphocytes;

In low doses, it stimulates the synthesis of interferons.

Thymogen (in the form of a solution for injections and a solution for instillation into the nose) is an even more purified and more active drug. It is possible to obtain it synthetically. Significantly superior in activity to taktivin.

A good effect when taking these drugs is achieved when:

Therapy of patients with rheumatoid arthritis;

With juvenile rheumatoid arthritis;

With recurrent herpetic lesions;

In children with lymphoproliferative diseases;

In patients with primary immunodeficiency;

With mucocutaneous candidiasis.

An essential condition for the successful use of thymus preparations is initially altered indicators of the function of T-lymphocytes.

Vilozen, a non-protein, low-molecular extract of bovine thymus, stimulates the proliferation and differentiation of T-lymphocytes in humans, inhibits the formation of reagins and the development of HRT. The best effect is achieved in the treatment of patients with allergic rhinitis, rhinosinusitis, hay fever.

Thymus preparations, in fact, being factors of the central organ of cellular immunity, correct exactly the T-link and macrophages of the body.

In recent years, new, more active agents have been widely used, the action of which is directed to B-lymphocytes and plasma cells. These substances are produced by the cells of the bone marrow. Based on low molecular weight peptides isolated from supernatants of animal and human bone marrow cells. One of the drugs in this group is B-activin or myelopid, which has a selective effect on the B-system of immunity.

Myelopid activates antibody-producing cells, selectively induces the synthesis of antibodies at the time of the maximum development of the immune response, enhances the activity of killer T-effectors, and also has an analgesic effect.

It has been proven that myelopid acts on currently inactive

time point of the population of B-lymphocytes and plasma cells, increasing the number of antibody-producers without increasing their production of antibodies. Myelopid also enhances antiviral immunity and is indicated primarily for:

Hematological diseases (chronic lymphocytic leukemia,

macroglobulinemia, myeloma);

Diseases accompanied by loss of protein;

Management of surgical patients, as well as after chemo- and lu

Chevoy therapy;

Bronchopulmonary diseases.

The drug is non-toxic and does not cause allergic reactions, does not give teratogenic and mutagenic effects.

Myelopid is prescribed subcutaneously at a dose of 6 mg, per course - 3 injections every other day, repeated 2 courses after 10 days.

Interferons (IF) - low molecular weight glycopeptides - a large group of immunostimulants.

The term "interferon" arose when observing patients who had a viral infection. It turned out that in the stage of convalescence they were protected, to one degree or another, from the effects of other viral agents. In 1957, the factor responsible for this viral interference phenomenon was discovered. Now the term "interferon" refers to a number of mediators. Although interferon is found in different tissues, it comes from different types of cells:

There are three types of interferons:

JFN-alpha - from B-lymphocytes;

JFN-beta - from epithelial cells and fibroblasts;

JFN-gamma - from T- and B-lymphocytes with the assistance of macrophages.

Currently, all three types can be obtained using genetic engineering and recombinant technology.

IFs also have an immunostimulatory effect by activating the proliferation and differentiation of B-lymphocytes. As a result, the production of immunoglobulins may increase.

Interferons, despite the diversity of genetic material in viruses, IF "intercept" their reproduction at the stage required for all viruses - blocking the start of translation, that is, the beginning of the synthesis of virus-specific proteins, and also recognize and discriminate viral RNA among cellular ones. Thus, IFs are substances with a universally broad spectrum of antiviral activity.

According to their composition, IF medical preparations are divided into alpha, beta and gamma, and according to the time of creation and use, they are divided into natural (I generation) and recombinant (II generation).

I Natural interferons:

Alpha-ferons - human leukocyte IF (Russia),

egiferon (Hungary), velferon (England);

Beta-ferons - toraiferon (Japan).

II Recombinant interferons:

Alpha-2A - reaferon (Russia), roferon (Switzerland);

Alpha-2B - intron-A (USA), inrek (Cuba);

Alpha-2C - Berofer (Austria);

Beta - betaseron (USA), fron (Germany);

Gamma - gammaferon (Russia), immunoferon (USA).

Diseases in the treatment of which IF is most effective are divided into 2 groups:

1. Viral infections:

The most studied (thousands of observations) are various herpetic

cue and cytomegalovirus lesions;

Less studied (hundreds of observations) acute and chronic

Russian hepatitis;

Influenza and other respiratory diseases are even less studied.

2. Oncological diseases:

hairy cell leukemia;

Juvenile papilloma;

Kaposi's sarcoma (AIDS marker disease);

Melanoma;

Non-Hodgkin's lymphomas.

An important advantage of interferons is their low toxicity. Only when using megadoses (in oncology) side effects are noted: anorexia, nausea, vomiting, diarrhea, pyrogenic reactions, leuko-thrombocytopenia, proteinuria, arrhythmias, hepatitis. The severity of complications causes an indication of the clarity of the indications.

A new direction in immunostimulating therapy is associated with the use of mediators of interlymphocyte relationships - interleukins (IL). It is known that IF, inducing the synthesis of IL, creates a cytokine network with them.

In clinical practice, 8 interleukins (IL1-8) are tested with certain effects:

IL 1-3 - stimulation of T-lymphocytes;

IL 4-6 - growth and differentiation of B cells, etc.

Clinical use data are available only for IL-2:

Significantly stimulates the function of T-helpers, as well as B-lim

phocytes and the synthesis of interferons.

Since 1983, IL-2 has been produced in recombinant form. This IL has been tested in immunodeficiencies caused by infection, tumors, bone marrow transplantation, rheumatic diseases, SLE, AIDS. The data are contradictory, there are many complications: fever, vomiting, diarrhea, weight gain, dropsy, rash, eosinophilia, hyperbilirubinemia - treatment regimens are being developed, doses are being selected.

A very important group of immunostimulating agents are growth factors. The most prominent representative of this group is leukomax (GM-CSF) or molgramostim (manufacturer - Sandoz). It is a recombinant human granulocyte-macrophage colony-stimulating factor (a highly purified water-soluble protein of 127 amino acids), thus an endogenous factor involved in the regulation of hematopoiesis and the functional activity of leukocytes.

Main effects:

Stimulates proliferation and differentiation of progenitors

hematopoietic organs, as well as the growth of granulocytes, monocy

tov, increasing the content of mature cells in the blood;

Quickly restores the body's defenses after chemotherapy

otherapy (5-10 mcg/kg once a day);

Accelerates recovery after autologous bone grafting

leg brain;

Possesses immunotropic activity;

Stimulates the growth of T-lymphocytes;

Specifically stimulates leukopoiesis (antileukopenic

means).

Herbal preparations

This group includes yeast polysaccharides, whose effect on the immune system is less pronounced than that of bacterial polysaccharides. However, they are less toxic, do not possess pyrogenicity, antigenicity. As well as bacterial polysaccharides, they activate the functions of macrophages and neutrophilic leukocytes. The drugs of this group have a pronounced effect on lymphoid cells, and this effect on T-lymphocytes is more pronounced than on B-cells.

Yeast polysaccharides - primarily zymosan (a biopolymer of the yeast shell of Saccharomyces cerevisi; in amp. 1-2 ml), glucans, dextrans are effective in infectious, hematological complications arising from radio and chemotherapy of cancer patients. Zimozan is administered according to the scheme: 1-2 ml intramuscularly every other day, 5-10 injections per course of treatment.

Yeast RNA is also used - sodium nucleinate (sodium salt of nucleic acid obtained by yeast hydrolysis and further purification). The drug has a wide range of effects, biological activity: regeneration processes are accelerated, bone marrow activity is activated, leukopoiesis is stimulated, phagocytic activity increases, as well as the activity of macrophages, T- and B-lymphocytes, nonspecific protection factors.

The advantage of the drug is that its structure is precisely known. The main advantage of the drug is the complete absence of complications when taking it.

Sodium nucleinate is effective in many diseases, but especially

It is specifically indicated for leukopenia, agranulocytosis, acute and prolonged pneumonia, obstructive bronchitis, it is also used in the recovery period in patients with blood pathology and in cancer patients.

The drug is used according to the scheme: inside 3-4 times a day, a daily dose of 0.8 g - a course dose - up to 60 g.

Synthetic immunoactive agents of different groups

1. Pyrimidine derivatives:

Methyluracil, orotic acid, pentoxyl, diucifon, oxymethacil.

In terms of the nature of the stimulating effect, the preparations of this group are close to yeast RNA preparations, since they stimulate the formation of endogenous nucleic acids. In addition, drugs of this group stimulate the activity of macrophages and B-lymphocytes, increase leukopoiesis and the activity of the components of the compliment system.

These funds are used as stimulants of leukopoiesis and erythropoiesis (methyluracil), anti-infective resistance, as well as to stimulate the processes of repair and regeneration.

Among the side effects are allergic reactions and the phenomenon of the opposite effect in severe leukopenia and erythropenia.

2. Derivatives of imidazole:

Levamisole, dibazol.

Levamisole (Levomisolum; in tablets of 0.05; 0.15) or decaris - a heterocyclic compound was originally developed as an anthelmintic drug, and it has also been proven to enhance anti-infective immunity. Levamisole normalizes many functions of macrophages, neutrophils, natural killers and T-lymphocytes (suppressors). The drug has no direct effect on B cells. A distinctive feature of levamisole is its ability to restore impaired immune function.

The most effective use of this drug in the following conditions:

Recurrent ulcerative stomatitis;

Rheumatoid arthritis;

Sjögren's disease, SLE, scleroderma (SCTD);

autoimmune disease (chronic progressive disease)

Crohn's disease;

Lymphogranulomatosis, sarcoidosis;

T-link defects (Wiskott-Aldridge syndrome, skin mucus

ty candidiasis);

Chronic infectious diseases (toxoplasmosis, leprosy,

viral hepatitis, herpes);

tumor processes.

Previously, levamisole was administered at a dose of 100-150 mg/day. New data have shown that the desired effect can be achieved with 1-3 ra

the initial administration of 150 mg / week, while the undesirable effects are reduced.

Among the side effects (frequency 60-75%), the following are noted:

Hyperesthesia, insomnia, headache - up to 10%;

Individual intolerance (nausea, decreased appetite

that, vomiting) - up to 15%;

Allergic reactions - up to 20% of cases.

Dibazol is an imidazole derivative, mainly used as an antispasmodic and antihypertensive agent, but has an immunostimulating effect by increasing the synthesis of nucleic acids and proteins. Thus, the drug stimulates the production of antibodies, enhances the phagocytic activity of leukocytes, macrophages, improves the synthesis of interferon, but acts slowly, therefore it is used to prevent infectious diseases (flu, SARS). For this purpose, dibazol is taken 1 time per day daily for 3-4 weeks.

There are a number of contraindications for use, such as severe liver and kidney disease, as well as pregnancy.

Regulatory peptides

The practical use of regulatory peptides makes it possible to most physiologically and purposefully influence the body, including the immune system.

The most comprehensively studied is Tuftsin, a tetrapeptide from the heavy chain region of immunoglobulin-G. It stimulates the production of antibodies, increases the activity of macrophages, cytotoxic T-lymphocytes, natural cells. In the clinic, tuftsin is used to stimulate antitumor activity.

From the group of oligopeptides, Dolargin (Dolarginum; powder in amp. or in a vial. 1 mg - diluted in 1 ml of saline solution; 1 mg 1-2 times a day, 15-20 days) is of interest - a synthetic analogue of enkephalins (biologically active substances of the class of endogenous opioid peptides, isolated in 1975).

Dolargin is used as an antiulcer drug, but studies have shown that it has a positive effect on the immune system, and more powerful than cimetidine.

Dolargin normalizes the proliferative response of lymphocytes in patients with rheumatic diseases, stimulates the activity of nucleic acids; generally stimulates wound healing, reduces the exocrine function of the pancreas.

The group of regulatory peptides has great prospects in the market of immunoactive drugs.

To select selective immunoactive therapy, a comprehensive quantitative and functional assessment of macrophages, T- and B-lymphocytes, their subpopulations is required, followed by the formulation of an immunological diagnosis and the choice of immunoactive drugs.

lective action.

The results of the study of the chemical structure, pharmacodynamics and pharmacokinetics, the practical use of immunostimulants do not give an unambiguous answer to many questions regarding the indications for immunostimulation, the choice of a specific drug, regimens and duration of treatment.

In the treatment with immunoactive agents, the individualization of therapy is determined by the following objective prerequisites:

The structural organization of the immune system, which is based on populations and subpopulations of lymphoid cells, monocytes and macrophages. Knowledge of the mechanisms of violation of the functions of each of these cells, changes in the relationship between them and underlies the individualization of treatment;

Typological disorders of the immune system in various diseases.

Thus, in patients with the same disease with a similar clinical picture, differences in changes in the functions of the immune system, pathogenetic heterogeneity of diseases are found.

In connection with the heterogeneity of pathogenetic disorders in the immune system, it is advisable to identify clinical and immunological variants of the disease for selective immunoactive therapy. To date, there is no single classification of immunostimulating agents.

Since the division of immunoactive drugs by origin, methods of preparation and chemical structure is not very convenient for clinicians, it seems more convenient to classify these drugs according to the selectivity of action on populations and subpopulations of monocytes, macrophages, T- and B-lymphocytes. However, an attempt at such a separation is complicated by the lack of selectivity of the action of existing immunoactive drugs.

The pharmacodynamic effects of drugs are due to the simultaneous inhibition or stimulation of T- and B-lymphocytes, their subpopulations, monocytes and effector lymphocytes. This results in unpredictability, unpredictability of the final effect of the drug and a high risk of undesirable consequences.

Immunostimulators also differ from each other in terms of their effect on cells. Thus, the BCG and C. parvum vaccine stimulates the function of macrophages more and has less effect on B- and T-lymphocytes. Thymomimetics (thymus preparations, Zn, levamisole), on the contrary, have a greater effect on T-lymphocytes than on macrophages.

Pyrimidine derivatives have a greater effect on nonspecific protective factors, and myelopids - on B-lymphocytes.

In addition, there are differences in the activity of the influence of drugs on a certain population of cells. For example, the effect of levamisole on macrophage function is weaker than that of BCG vaccines. These properties of immunostimulating drugs can be the basis for their

classifications according to their relative selectivity of the form-dynamic effect.

Relative selectivity of the pharmacodynamic effect

immunostimulants:

1. Drugs that primarily stimulate non-specific

protection factors:

Purine and pyrimidine derivatives (isoprinosine, methyluracil, oxymethacyl, pentoxyl, orotic acid);

Retinoids.

2. Drugs primarily stimulating monocytes and poppy

sodium nucleinate; - muramylpeptide and its analogues;

Vaccines (BCG, CP) - vegetable lipopolysaccharides;

Lipopolysaccharides of Gr-negative bacteria (pyrogenal, biostim, prodigiosan).

3. Drugs that primarily stimulate T-lymphocytes:

Imidazole compounds (levamisole, dibazol, immunitiol);

Thymus preparations (timogen, taktivin, thymalin, vilozen);

Zn preparations; - lobenzarite Na;

Interleukin-2 - thiobutarit.

4. Drugs that primarily stimulate B-lymphocytes:

Myelopids (B-activin);

Oligopeptides (tuftsin, dalargin, rigin);

Low molecular weight immunocorrectors (bestatin, amastatin, forfenicin).

5. Predominantly natural stimulants

killer cells:

Interferons;

Antiviral drugs (isoprinosine, tilorone).

Despite a certain conventionality of the proposed classification, this division is necessary, as it allows prescribing drugs based on immunological rather than clinical diagnosis. The absence of drugs with selective action significantly complicates the development of combined immunostimulation methods.

Thus, for the individualization of immunoactive therapy, clinical and immunological criteria are needed to predict the outcome of treatment.

Partially purified components

• * nucleic acids: sodium nucleinate, ridostin
• * lipopolysaccharides: prodigiosan, pyrogenal
• * peptidoglycans (membrane fractions of bacteria) and ribosomes (ribomunyl)

Bacterial lysates with vaccine effect

• * polypathogenic: IRS-19, imudon, bronchomunal
• * monopathogenic: posterizan, ruzam, solkotrikhovak

Synthetic analogue of bacterial membrane fractions (minimal biologically active fragments)

• * glucosaminemuramylpeptide (lycopid)
• * СрG oligonucleotides (Promun, Actilon, Waximmun)

Immunotropic drugs of animal origin(organ preparations)

• * thymus gland: T-activin, thymalin, vilozen, thymoptin, thymulin, etc.
• * Bovine embryonic tissue: Erbisol
• * porcine bone marrow: myelopid (B-activin)
• * spleen: splenin
• * placenta: placenta extract
• * blood: histaglobulin, pentaglobin and other immunoglobulin preparations

Preparations from beekeeping products are bee pollen, apilak (powder of native royal jelly of bees), etc.

Pharmacological preparations plant origin(adaptogens)

• * Quercetin (from Japanese Sophora)
• * echinacin, immunal, esberitox, echinacea tincture (from echinacea purpurea)
• * Rhodiola rosea liquid extract
• * tincture of ginseng root, Schisandra chinensis fruit, royal jelly; tincture of ginseng
• * phytovit (extract of 11 plants)
• * fruits, syrup, rosehip oil solution
• * glycyram (from licorice root)
• * ukrain (celandine extract)

In most cases, all of the listed immunotropic drugs have a complex effect on the immune system. Therefore, their division into groups according to the predominant effect on individual parts of the immune system is conditional, but at the same time acceptable in clinical practice.

So, to correct violations functions of cells of the monocyte-macrophage system effective: methyluracil, pentoxyl, sodium nucleinate, polyoxidonium, lycopid, lysobact, ribomunil, etc.

At T-cell dysfunction immunity, you can use one of the following drugs: T-activin, thymogen, thymalin, vilozen, immunofan, polyoxidonium, levamisole, sodium nucleinate, erbisol, diucifon, vitamins A, E, trace elements, etc.

In case of dysfunction B-cell link of immunity it is necessary to prescribe such agents as myelopid, polyoxidonium, immunoglobulin preparations, bacterial polysaccharides (pyrogenal, prodigiosan), immunofan, splenin, microelements, etc.

For stimulation natural killers interferon preparations are used: natural - egiferon (human leukocyte), feron (human fibroblast), IFN-g (human immune); recombinant - reaferon, ladiferon, v-feron, g-feron, etc.; synthetic inducers of endogenous interferon - cycloferon, mefenamic acid, dibazol, kagocel, amixin, groprinasin, amizon, mustard plasters (interferon inducers at the site of application), etc.

Basic principles for the use of immunomodulators:

• 1. The drugs are not used independently, but only supplement traditional therapy.
• 2. Before prescribing MI, it is obligatory to assess the nature of immunological disorders in a patient.
• 3. Take into account the dependence of changes in immunological parameters on the age, biological rhythms of the patient and other reasons.
• 4. It is necessary to determine the severity of immunological disorders.
• 5. Take into account the immunotropic effects of traditional medicines.
• 6. Take into account the targets of the selected correctors and their combinations.
• 7. Take into account the adverse reactions of drugs and their combinations.
• 8. Remember that the profile of the action of modulators is preserved in various diseases, not only in the presence of the same type of immunological disorders.
• 9. The nature of immunological disorders in a patient can change the spectrum of action of MI.
• 10. The severity of the correction effect in the acute period is higher than in the remission stage.
• 11. The duration of the elimination of immunological disorders ranges from 30 days to 6-9 months and depends on the properties of the drug, the marker indicator and the nature of the disease.
• 12. With repeated administration of MI, the spectrum of their action is preserved, and the severity of the effect increases.
• 13. MI, as a rule, does not affect unchanged immunological parameters.
• 14. Elimination of deficiency of one link of immunity, as a rule, compensates for stimulation of another link.
• 15. Drugs fully realize their effects only when used in optimal doses.
• 16. Determine the patient's response to certain MIs.

From the immunobiological standpoint, the state of health of modern man and humanity as a whole is characterized by two features: a decrease in the immunological reactivity of the population as a whole and, as a result, an increase in acute and chronic morbidity associated with opportunistic microorganisms.

The result of this is an unusually great interest of doctors of almost all specialties in the problem of immunotherapy. Drugs that affect the immune system are beginning to be widely used in clinical practice for a wide variety of diseases, often qualified and justified, but sometimes without sufficient reason. First of all, it is necessary to define what is meant by the term "immunotropic drugs". According to M. D. Mashkovsky, drugs that correct the processes of immunity (immunocorrectors) are divided into drugs that stimulate the processes of immunity, and immunosuppressive drugs (immunosuppressors). But it is possible to single out the third group of this class - immunomodulators, that is, substances that have a multidirectional effect on the immune system, depending on its initial state. This implies that such a drug increases low and reduces elevated levels of immune status. Thus, according to the effect of action on the immune system, drugs can be divided into immunosuppressors, immunostimulants and immunomodulators.

Extraimmune and intrinsic immunotherapy. Any substance that has some effect on the body will eventually affect the immune system, such as vitamins, trace elements, etc. It is also obvious that there are and should be drugs with a predominant effect on the immune system. In this regard, conditionally immunotherapy can be divided into extra-immune and proper immunotherapy. In the first case, a complex of actions is used to eliminate the cause of immunodeficiency, and a complex of drugs that improve the general condition of the body, increase its nonspecific resistance. In the second case, a complex of effects and drugs is used mainly to improve the functioning of the immune system itself. This division is conditional, like any other that concerns a living system. It is quite obvious that drugs, the impact of which is aimed at improving the general condition of the body - vitamins, adaptogens, trace elements, etc. - will affect the cells of the immune system. It is also obvious that those drugs that primarily affect the immune system will act directly or indirectly on other organs and tissues of the body. Extraimmunotherapy aims to reduce the antigenic load on the body, for example, the appointment of a hypoallergenic diet, treatment of chronic foci of infection: antibiotic therapy with the simultaneous use of lactobifidumbacterin and specific immunotherapy methods (staphylococcal toxoid, antiphagin, etc.), specific desensitization (specific immunotherapy), as well as non-specific hyposensitization with drugs of gamma globulins, pentoxyl, the use of vitamins, microelements, etc.

In this way, extraimmune therapy consists in the appointment of a complex of non-specific means and effects aimed at improving the general condition of the body, metabolism. Its principle can be defined by paraphrasing the well-known proverb: "In a healthy body - a healthy immune system." The selection of this non-specific complex of influences into an independent section of immunotherapy is done with only one goal: to force the doctor, before prescribing a specific treatment, to try to find out the cause of the immunological deficiency in this patient, the possibility of eliminating it without the help of strong agents and to develop a complex treatment, which, if necessary, will consist of both extraimmune, and from the proper immunotherapy.

All components of the immune system, like any other feature of the body, are genetically determined. But their expression depends on the antigenic environment in which the given organism is located. In this regard, the level of functioning of the immune system existing in the body is the result of the interaction of auxiliary (macrophages and monocytes) and immunocompetent (T- and B-lymphocytes) cells with a constant flow of antigens entering its internal environment. These antigens are the driving force behind the development of immunity, acting as a first push. But then the immune response can develop relatively independently of the influence of the antigen: the second echelon of immune system regulators comes into play - cytokines, on which the activation, proliferation and differentiation of immunocompetent cells largely depend. This can be seen especially clearly in the model of the central cell of the immune system T-helper. Under the influence of antigen and cytokines - gamma-interferon, IL-12 and transforming growth factor - it differentiates into T1 helpers, under the influence of IL-4 into T2 helpers. The development of all immunological reactions depends on the cytokines synthesized by these subpopulations and macrophages:

• · INF and TNF - lymphokine-mediated cellular and antibody-dependent cellular cytotoxicity, phagocytosis and intracellular killing;
• IL-4,5,10,2 - antibody formation;
• · IL-3,4,10 - release of mediators from mast cells and basophils.

Obviously, almost all natural substances that have the ability to affect the immune system can be divided into exogenous and endogenous. The vast majority of the former are substances of microbial origin, mainly bacterial and fungal. Herbal preparations are also known (soap tree bark extract, polysaccharide from potato seedlings - vegetative).

Substances endogenous origin according to the history of their appearance can be divided into two groups:

• on immunoregulatory peptides
• cytokines.

The former are mainly an extract from the organs of the immune system (thymus, spleen) or their metabolic products (bone marrow). Thymus preparations may contain thymus hormones. Under the second understand the totality of biologically active proteins produced by lymphocytes and macrophages: interleukins, monokines, interferons. In immunotherapy, they are used as recombinant preparations.

A third group of drugs should be distinguished:

Synthetic and (or) chemically pure.

Conventionally, they can be divided into three subgroups:

A) analogues of preparations of microbial or animal origin;

B) well-known medicinal preparations with additional immunotropic properties;

C) substances obtained as a result of directed chemical synthesis. Analyzing the historical development of the doctrine of ITLS, it should be noted that domestic researchers were at the origins of almost all areas of this doctrine.

Classification of the main types immunotropic drugs (ITLS

The basis for immunotherapy are the results of clinical and immunological studies. Based on the data of this survey, 3 groups of people can be distinguished:

• 1. Persons with clinical signs of impaired immunity and changes in immunological parameters.
• 2. Persons with clinical signs of impaired immune system in the absence of changes in immunological parameters detected using routine laboratory tests.
• 3. Persons with only changes in immunological parameters without clinical signs of immune system deficiency.

It is obvious that patients of group 1 should receive immunotherapy and scientifically based choice of drugs for people in this group is relatively easy or, more precisely, possible. The situation is more difficult with persons of the 2nd group. Without a doubt, an in-depth analysis of the state of the immune system i.e. analysis of the functioning of the activity of the phagocytic, T-B-systems of immunity, as well as complement systems, in most cases will reveal the defect and, consequently, the cause of immunological deficiency. At the same time, patients with clinical signs of immunological deficiency should also receive ITLS, and the basis for their appointment is only the clinical picture of the disease. Based on it, an experienced doctor can make a preliminary diagnosis and make an assumption about the level of damage to the immune system. For example, frequent bacterial infections, such as otitis and pneumonia, are most often the result of a defect in the humoral link of immunity, while fungal and viral infections usually indicate a predominant defect in the T-system of immunity. Based on the clinical picture, it can be assumed that there is a deficiency in the secretory IgA system, according to the different sensitivity of the macroorganism to pathogenic microbes, one can judge a defect in the biosynthesis of IgG subclasses, defects in the complement system and phagocytosis. Despite the absence of visible changes in the parameters of the immune system in patients of group 2, the course of immunotherapy should still be carried out under the control of the assessment of the immune status using the methods that the laboratory currently owns. Group 3 is more difficult. With regard to these individuals, the question arises whether the identified changes will lead to the development of a pathological process or the compensatory capabilities of the organism as a whole and the immune system, in particular, will not allow them to develop. In other words, is the revealed picture of the immune status (or has it become) the norm for this individual? It is believed that this contingent needs immunological monitoring.

foreign agents of both exogenous and endogenous nature. 4 main protective mechanisms take part in this protection: phagocytosis, complement system, cellular and humoral immunity. Accordingly, secondary immunodeficiency states can be associated with a violation of each of these protective mechanisms. The task of clinical and immunological examination is to identify the impaired link of immunity in order to conduct reasonable immunotherapy. Almost the main target of action of drugs of microbial origin are the cells of the monocyte-macrophage system, the natural task of which is the elimination of the microbe from the body. They enhance the functional activity of these cells, stimulating phagocytosis and microbicidal activity. In parallel with this, the activation of the cytotoxic function of macrophages occurs, which is manifested by their ability to destroy syngeneic and allogeneic tumor cells in vivo. Activated monocytes and macrophages begin to synthesize a number of cytokines: IL1, IL3, TNF, colony-stimulating factor, etc. The consequence of this is the activation of both humoral and cellular immunity.

A prime example of this is the lycopid. This drug in low doses enhances the absorption of bacteria by phagocytes, the formation of reactive oxygen species by them, the killing of microbes and tumor cells, stimulates the synthesis of IL-1 and TNF.

The immunostimulatory effect of INF and leukomax is also largely associated with their effect on the cells of the monocyte-macrophage system. The first has a pronounced ability to stimulate NK cells, which play an important role in antitumor protection.

Naturally, T- and B-lymphocytes, respectively, serve as targets for the action of drugs of thymic and bone marrow origin. As a result, their proliferation and differentiation are enhanced. In the first case, this is manifested by the induction of the synthesis of cytokines by T cells and an increase in their cytotoxic properties, in the second case, by an increase in the synthesis of antibodies. Levamisole and diucifon, which can be classified as thymomitic drugs, have a pronounced ability to have a stimulating effect on the T-system. The latter is an IL-2 inducer and therefore has the ability to stimulate the NK cell system as well.

An important question is about drugs belonging to the group of immunomodulators proper. All of them are immunostimulants according to the mechanism of their action. However, in autoimmune diseases, the goal of therapeutic action is to suppress unwanted autoimmunity. Currently, immunosuppressants are used for these purposes: cyclosporine A, cyclophosphamide, glucocorticoids, etc., which, along with obvious positive effects, also cause a number of adverse reactions. In this regard, the development and use of ITLS, which normalize immune processes without causing a sharp suppression of the immune system, is one of the urgent tasks of immunopharmacology and immunotherapy. A good example of a drug with immunomodulatory properties is licopid. In appropriate doses, it has the ability to suppress the synthesis of anti-inflammatory cytokines IL1 and TNF, which is associated with increased formation of antagonists of these cytokines. This is probably why licopid causes a high therapeutic effect in such an autoimmune disease as psoriasis.

The ITLS teaching has a short history - about 20 years. However, significant progress has been made during this period of time, which could be generally defined as quantitative. They consist in creating a fairly large set of drugs that act on the main components of the immune system: phagocytosis, humoral, cellular immunity. However, this list, of course, should change and expand.

First of all, it is necessary to define what is meant by the term "immunotropic drugs". M.D. Mashkovsky divides drugs that correct the processes of immunity (immunocorrectors) into immunostimulating and immunosuppressive drugs (immunosuppressors). A third group can also be distinguished - immunomodulators, that is, substances that have an effect on the immune system depending on its initial state. Such drugs increase low and reduce high levels of immune status. Thus, according to the effect on the immune system, immunotropic drugs can be divided into immunosuppressors, immunostimulants and immunomodulators.

This section is devoted only to the last two types of drugs and mainly to immunostimulants.

Characteristics of immunomodulators

Preparations of bacterial and fungal origin

Vaccines-immunomodulators Vaccines from opportunistic bacteria not only increase resistance to a particular microbe, but also have a powerful non-specific immunomodulatory and stimulating effect. This is due to the presence in their composition of lipopolysaccharides, proteins A, M and other substances of the strongest activators of immunity, acting as adjuvants. An indispensable condition for the appointment of immunomodulatory therapy with lipopolysaccharides should be a sufficient level of target cells (ie, the absolute number of neutrophils, monocytes and lymphocytes).

Bronchomunal ( Bronchos - Munal ) - lyophilized bacteria lysate { str. pneumoniae, H. influence, str. vindans, str. pyogenes, moraxella catarrhalts, S. aureus, K. pneumoniae and Kozaenae). Increases the number of T-lymphocytes and IgG, IgM, clgA antibodies, IL-2, TNF; used in the treatment of infectious diseases of the upper respiratory tract (bronchitis, rhinitis, tonsillitis). The capsule contains 0.007 g of lyophilized bacteria, 10 per pack. Assign 1 capsule per day for 10 days a month for 3 months. Children are prescribed bronchomunal II, which contains 0.0035 g of bacteria per capsule. Apply in the morning on an empty stomach. Dyspeptic phenomena, diarrhea, pain in the epigastrium are possible.

Ribomunil ( Ribomunyl ) - contains immunomodulatory substances represented by a combination of bacterial ribosomes (Klebsiella pneumoniae - 35 stakes Streptococcus pneumoniae - 30 shares, Streptococcus pyogenes - 30 shares, Haemophilia influenzae - 5 shares) and membrane proteoglycans Kpneumoniae. It is prescribed 1 tablet 3 times a day or 3 tablets to be taken in the morning, on an empty stomach, in the first month - 4 days a week for 3 weeks, and in the next 5 months. - 4 days at the beginning of each month. Forms immunity to infectious agents, provides long-term remission in chronic bronchitis, rhinitis, tonsillitis, otitis media.

Multicomponent vaccine (VP-4 - Immunovak) is an antigenic complexes isolated from Staphylococcus, Proteus, Klebsiella pneumonia and Escherichia coli K-100; induces in the vaccinated the production of antibodies to these bacteria. In addition, the drug is a stimulant of nonspecific resistance, increasing the body's resistance to conditionally pathogenic bacteria. Correlates the level of T-lymphocytes, enhances the synthesis of IgA and IgG in the blood and slgA in saliva, stimulates the formation of IL-2 and interferon. The vaccine is intended for immunotherapy of patients (aged 16-55 years) with chronic inflammatory and obstructive respiratory diseases (chronic bronchitis, chronic obstructive pulmonary disease, infection-dependent and mixed forms of bronchial asthma). Intranasally administered: 1 day - 1 drop in one nasal passage; 2 days - 1 drop in each nasal passage; 3 days - 2 drops in each nasal passage. Starting from the 4th day after the start of immunotherapy, the drug is injected under the skin of the subscapular region 5 times with an interval of 3-5 days, alternately changing the direction of administration. 1st injection - 0.05 ml; 2nd injection 0.1 ml; 3rd injection - 0.2 ml; 4th injection - 0.4 ml; 5 injection - 0.8 ml. When the vaccine is administered orally, 1-2 days after the end of intranasal administration, the drug is taken orally 5 times with an interval of 3-5 days. 1 dose - 2.0 ml; 2 reception - 4.0 ml; 3 reception - 4.0 ml; 5 reception - 4.0 ml.

Staphylococcal vaccine contains a complex of thermostable antigens. It is used to create anti-staphylococcal immunity, as well as to increase overall resistance. It is administered subcutaneously at a dose of 0.1-1 ml daily for 5-10 days.

Imudon ( Imudon ) - the tablet contains a lyophilic mixture of bacteria (lactobacilli, streptococci, enterococci, staphylococci, klebsiella, corynebacteria pseudodiphtheria, fusiform bacteria, candida albicans); used in dentistry for periodontitis, stomatitis, gingivitis and other inflammatory processes of the oral mucosa. Assign 8 tablets / day (1-2 in 2-3 hours); the tablet is kept in the mouth until completely dissolved.

IRS-19 ( IRS -19) - dosed aerosol for intranasal use (60 doses, 20 ml) contains a lysate of bacteria (pneumonia diplococci, streptococci, staphylococci, neisseria, klebsiella, morahella, influenza bacillus, etc.) . Stimulates phagocytosis, increases the level of lysozyme, clgA. Used for rhinitis, pharyngitis, tonsillitis, bronchitis, bronchial asthma with rhinitis, otitis media. Make 2-5 injections per day in each nostril until the infection disappears.

Bacterialand yeast substances

sodium nucleinate The drug in the form of a sodium salt of nucleic acid is obtained by hydrolysis of yeast cells with subsequent purification. It is an unstable mixture of 5-25 types of nucleotides. It has a pluripotent stimulating activity against immune cells: it increases the phagocytic activity of micro- and macrophages, the formation of active acid radicals by these cells, which leads to an increase in the bactericidal action of phagocytes, and increases the titers of antitoxic antibodies. It is prescribed orally in tablets in the following doses per 1 dose: children of the 1st year of life - 0.005-0.01 g each, from 2 to 5 years old - 0.015-002 g each, from 6 to 12 years old - 0.05-0. .1 g. The daily dose consists of two to three single doses, calculated on the age of the patient. Adults receive no more than 0.1 g per 1 dose 4 times a day.

Pyrogenal The drug was obtained from a culture Pseudomonas aeroginosa. Low toxicity, but causes fever, short-term leukopenia, which is then replaced by leukocytosis. The effect on the cell system of the phagocytic system is especially effective, therefore it is often used in the complex therapy of protracted and chronic inflammatory diseases of the respiratory tract and other localizations. It is administered intramuscularly. Injections are not recommended for children under 3 years of age. Children over 3 years old are given a dose of 3 to 25 mcg (5-15 MPD - minimum pyrogenic doses) per injection, depending on age, but not more than 250-500 MTD. For adults, the usual dose is 30-150 mg (25-50 MPD) per injection, the maximum is 1000 MPD. The course of therapy includes from 10 to 20 injections, and monitoring of peripheral blood and immune status is necessary.

Pyrogenal test - a test for leukopenic conditions to stimulate an emergency release of immature forms of granulocytes from cell depots. The drug is administered at a dose of 15 MPD per 1 m 2 of body area. Another calculation formula is 0.03 µg per 1 kg of body weight. Contraindicated in pregnancy, acute fevers, leukopenia of autoimmune origin.

Yeast preparations contain nucleic acids, a complex of natural vitamins and enzymes. They have long been used for bronchitis, furunculosis, long-healing ulcers and wounds, anemia, in the recovery period after serious illness. To 5 - 10 g of yeast add 30 - 50 ml of warm water, grind and incubate for 15-20 minutes in a warm place until foam forms. The mixture is shaken and drunk 15-20 minutes before meals 2-3 times a day for 3-4 weeks. The clinical effect appears in a week, immunological - later. To reduce dyspepsia, the drug is diluted with milk or tea.

Synthetic immunomodulators

Likopid Semi-synthetic drug, refers to muramyl dipeptides, similar to bacterial ones. It is a fragment of the bacterial cell wall. Derived from the cell wall M. lysodeicticus.

The drug increases the overall resistance of the organism to a pathogenic factor, primarily due to the activation of cells of the phagocytic immune system (neutrophils and macrophages). In case of suppressed hematopoiesis, for example, caused by chemotherapy or radiation, the use of licopide leads to the restoration of the number of neutrophils. Likopid activates T- and B-lymphocytes.

Indications: acute and chronic purulent-inflammatory diseases; acute and chronic respiratory diseases; damage to the cervix by the human papillomavirus; vaginitis; acute and chronic viral infections: ophthalmic herpes, herpetic infections, shingles; pulmonary tuberculosis; trophic ulcers; psoriasis; immunoprophylaxis of colds.

Appoint courses depending on the disease. In chronic infections of the respiratory tract (bronchitis) in the acute stage, 1-2 tablets (1-2 mg) under the tongue - 10 days. With prolonged recurrent infections, 1 tablet (10 mg) 1 time per day for 10 days. Pulmonary tuberculosis: 1 tablet (10 mg) - 1 time under the tongue for 3 cycles of 7 days at intervals of 2 weeks. Herpes (mild forms) - 2 tabs (1 mg x 2) 3 times a day under the tongue for 6 days; in severe cases - 1 tab (10 mg) 1-2 times a day inside - 6 days. Children are prescribed tablets of 1 mg.

Contraindicated in pregnancy. An increase in body temperature up to 38 ° C, which sometimes occurs after taking the drug, is not a contraindication.

Rheosorbilact - used for detoxification. Apparently, it has an immunomodulatory effect in the treatment of chronic obstructive pulmonary diseases, rheumatism, intestinal infections. Enter adults 100-200 ml, children 2.5 - 5 ml / kg, intravenous drip (40-80 drops per 1 min) every other day.

Dibazol ( Dibazolum ) - vasodilator, antihypertensive agent. The drug has adaptogenic and interferogenic effects, enhances the synthesis of proteins and nucleic acids, the expression of IL-2, receptors on N-helpers. Used for acute infections (bacterial and viral). Optimal, apparently, should be considered a combination of dibazol with licopid. It is prescribed in tablets of 0.02 (single dose - 0.15 g), ampoules 1; 2; 5 ml 0.5°/, or 1% solution for 7-10 days. Children of early age - 0.001 g / day, up to ] year - 0.003 g / day, preschool age 0.0042 g / day.

Blood pressure should be monitored, especially in adolescents, in whom dibazol can cause dysregulation of vascular tone.

Dimexide (dimethyl sulfoxide) available in 100 ml bottles, liquid with a specific odor, has a unique penetrating ability into tissues, pH 11. It has anti-inflammatory, anti-edematous, bactericidal and immunomodulatory effects. Stimulates phagocytes and lymphocytes. In rheumatology, a 15% solution is used in the form of applications for joints in rheumatoid arthritis. Used for purulent-septic and bronchopulmonary diseases. Course 5-10 applications.

Isoprinazine (groprin azine ) - a mixture of 1 part of inosine and 3 parts of p-aceto-amidobenzoic acid. Stimulates phagocytic cells and lymphocytes. Stimulates the production of cytokines, IL-2, which significantly changes the functional activity of peripheral blood lymphocytes and their specific immunological functions: differentiation of 0-cells into T-lymphocytes is induced, and the activity of cytotoxic lymphocytes is enhanced. Almost non-toxic and well tolerated by patients. Side effects and complications are not described. Possessing a pronounced interferonogenic effect, it is used in the treatment of acute and protracted viral infections (herpetic infection, measles, hepatitis A and B, etc.). Stimulates mature B cells. It is taken orally in the form of tablets (1 tab. 500 mg) at a dose of 50-100 mg per 1 kg of body weight per day. The daily dose is divided into 4-6 doses. The duration of the course is 5-7 days. Indications: secondary immunodeficiency diseases, especially in herpetic infections.

Imunofan ( Imunofan ) - hexapeptide (arginyl-alpha-aspartyl-lysyl-valine-tyrosyl-arginine) has an immunoregulatory, detoxifying, hepatoprotective effect and causes inactivation of free radical and peroxide compounds. The action of the drug develops within 2-3 hours and lasts up to 4 months; normalizes lipid peroxidation, inhibits the synthesis of arachidonic acid, followed by a decrease in blood cholesterol levels and the production of inflammatory mediators. After 2-3 days, it enhances phagocytosis. The immunocorrective effect of the drug appears after 7-10 days, enhances the proliferation of T-lymphocytes, increases the production of interleukin-2, the synthesis of antibodies, interferon. Ampoules contain 1 ml of a 0.005% solution of the drug (packing of 5 ampoules). Assign subcutaneously, intramuscularly daily or after 1-4 days 1 course 5-15 injections. With herpes infection, cytomegalovirus, toxoplasmosis, chlamydia, pneumocystosis 1 injection every two days, the course of treatment is 10-15 injections.

Galavit ( Galavit ) - a derivative of aminophthalhydrozide with anti-inflammatory and immunomodulatory activity. It is recommended for secondary immune deficiency and chronic recurrent, sluggish infections of various organs and localizations. Assign intramuscularly at 200 mg 1 dose, then 100 mg 2-3 times a day until intoxication decreases or inflammation ceases. Maintenance course in 2-3 days. Approbated for furunculosis, intestinal infections, adnexitis, herpes, cancer chemotherapy; inhalation in chronic bronchitis.

Polyoxidonium - a synthetic immunomodulator of a new generation, an N-oxidized derivative of polyethylene piperazine, which has a wide spectrum of pharmacological action and high immunostimulatory activity. Its predominant effect on the phagocytic link of immunity has been established.

Main pharmacological properties: activation of phagocytes and the digestive capacity of macrophages against pathogenic microorganisms; stimulation of cells of the reticuloendothelial system (capture, phagocytize and remove foreign microparticles from the circulating blood); increased adhesion of blood leukocytes and their ability to produce reactive oxygen species upon contact with opsonized fragments of microorganisms; stimulation of cooperative T- and B-cell interaction; increase in the body's natural resistance to infections, normalization of the immune system in secondary IDS; antitumor activity. Polyoxidonium is prescribed to patients once a day in / m, using doses from 6 to 12 mg. The course of administration of polyoxidonium is from 5 to 7 injections, every other day or according to the scheme: 1-2-5-8-11-14 days of drug administration.

Methyluracil stimulates leukopoiesis, enhances cell proliferation and differentiation, antibody production. Assign inside for 1 reception: children from 1-3 years old - 0.08 g each, from 3-8 years old - 0.1 - 0.2 g each; from 8-12 years old and adults - 0.3-0.5 g each. Patients are given 2-3 single doses per day. The course lasts 2-3 weeks. With secondary immunological insufficiency, it is used in patients with moderate cytopenic conditions.

Theophylline stimulates suppressor T cells at a dose of 0.15 mg 3 times a day for 3 weeks. At the same time, not only a decrease in the number of B-cells is noted, but also a suppression of their functional activity. It can be used in the treatment of autoimmune diseases and autoimmune syndrome in immunodeficiency. However, the main purpose of the drug is the treatment of bronchial asthma, since it has a bronchodilator effect.

famotidine - blockers of H2 histamine receptors, inhibit T-suppressors, stimulate T-helpers, expression of IL-2 receptors and the synthesis of immunoglobulins.

Interferon inducers stimulate the production of endogenous interferon.

Amiksin - stimulates the formation of α, β, and gamma interferons, enhances antibody production, has an antibacterial and antiviral effect. Used to treat hepatitis A and enterovirus infections (1 tab. - 0.125 g for adults and 0.06 - for children for 2 days , then take a break of 4-5 days, the course of treatment is 2-3 weeks), for the prevention of viral infections (influenza, acute respiratory infections, SARS) - 1 table. Once a week, 3-4 weeks. Contraindicated in pregnancy, diseases of the liver, kidneys.

Arbidol - an antiviral drug. It has an inhibitory effect on influenza A and B viruses. It has interferon-inducing activity and stimulates humoral and cellular immune responses. Release form: tablets of 0.1 g. For the treatment of viral infections, 0.1 g is prescribed three times a day before meals for 3-5 days, then 0.1 g 1 time per week for 3-4 weeks . Children 6-12 years old: 0.1 g every 3-4 days for 3 weeks prophylactically during an influenza epidemic. In the treatment: children - 0.1 g 3-4 times a day for 3-5 days. Contraindicated in patients with cardiovascular diseases, diseases of the liver and kidneys.

Neovir - induces the synthesis of alpha-interferon, activates stem cells, NK cells, T-lymphocytes, macrophages, reduces the level of TNF-α. In the acute period of herpes infection, 3 injections of 250 mg are prescribed at an interval of 16-24 hours and 3 more injections at an interval of 48 hours. In the interrecurrent period, 1 injection per week at a dose of 250 mg for a month. With urogenital chlamydia 5-7 injections of 250 mg with an interval of 48 hours. Antibiotics are prescribed on the day of the second injection. Produced as a sterile solution for injection in 2 ml ampoules containing 250 mg of the active substance in 2 ml of a physiologically compatible buffer. Pack of 5 ampoules.

Cycloferon - 12.5% ​​solution for injection - 2 ml, tablets of 0.15 g, ointment 5% of 5 ml. Stimulates the formation of α, β, and γ-interferons (up to 80 U / ml), increases the level of CD4 + and CD4 + T-lymphocytes in HIV infection. Recommended for herpes, cytomegalovirus infection, hepatitis, HIV infection, multiple sclerosis, gastric ulcer, rheumatoid arthritis. A single dose of 0.25-0.5 g intramuscularly or intravenously on days 1, 2, 4, 6, 8, 11, 14, 17, 20, 23, 26, 29. Children 6-10 mg / kg / day - in / in or / m. Tablets of 0.3 - 0.6 g 1 time per day. Assign for influenza and respiratory infections; ointment - for herpes, vaginitis, urethritis.

Kagocel - a synthetic drug based on carboxymethylcellulose and polyphenol - gossypol. Induces the synthesis of α and β-interferons. After a single dose, they are produced within a week. Tablets of 12 mg. For the treatment of influenza and SARS, adults are prescribed in the first two days - 2 tablets 3 times a day, in the next two days - one tablet 3 times a day. In total, the course - 18 tablets, the duration of the course - 4 days. Prevention of respiratory viral infections in adults is carried out in 7-day cycles: two days - 2 tablets 1 time per day, 5 days break, then repeat the cycle. The duration of the prophylactic course is from one week to several months. For the treatment of herpes in adults, 2 tablets are prescribed 3 times a day for 5 days. Total for the course - 30 tablets, course duration - 5 days. For the treatment of influenza and acute respiratory viral infections, children aged 6 years and older are prescribed in the first two days - 1 tablet 3 times a day, in the next two days - one tablet 2 times a day. Total for the course - 10 tablets, course duration - 4 days.

Immunofan and dibazole - (see above) are also interferonogens.

Dipyridamole (chimes) - a vasodilator drug, used 0.05 g 2 times a day with an interval of 2 hours once a week increases the level of gamma-interferon, stops viral infections.

Anaferon - contains low doses of antibodies to gamma-interferon, therefore it has immunomodulatory properties. Used for viral infections of the upper respiratory tract (influenza, SARS) 5-8 tablets on the 1st day and 3 on the 2nd - 5th day. For prevention - 0.3 g - 1 tablet for 1-3 months.

Preparations derived from cells and organs of the immune system

Thymic peptides and hormones The most important feature of thymic peptides (derived from epithelioid, stromal cells, Hassall's bodies, thymocytes, etc.) as hormones is the short duration and short distance of their action on target cells. This largely determines the therapeutic tactics. Medicinal preparations are obtained in various ways from animal thymus extracts.

Thymus peptides have the property common to the whole group to enhance the differentiation of cells of the lymphoid system, changing not only the functional activity of lymphocytes, but also causing the secretion of cytokines, such as IL-2.

Indications for prescribing this group of drugs are clinical and laboratory signs of T-cell immunity deficiency: infectious or other syndromes associated with immunological deficiency; lymphopenia, decrease in the absolute number of T-lymphocytes, the index of the ratio of CD4 + /CD8 + lymphocytes, proliferative response to mitogens, depression of delayed-type hypersensitivity reactions in skin tests, etc. .

Thymic insufficiency may be acute and chronic. Acute thymic insufficiency is formed during intoxication, physical or psycho-emotional stress, against the background of severe acute infectious processes. Chronic characterizes T-cell and combined forms of immunodeficiency. Thymic insufficiency should not be corrected by immunostimulatory effects, it should be replaced by preparations of thymus hormone peptides.

Replacement therapy for acute thymus insufficiency usually requires a short course of thymus peptide saturation against the background of symptomatic therapy. Chronic thymus insufficiency is replaced by regular courses of thymus peptides. Usually, the first 3-7 days, the drugs are administered in saturation mode, and then continue as maintenance therapy.

Congenital forms of immunological deficiency of the T-cell type almost uncorrected by thymic factors, usually due to genetically determined defects in target cells or the production of mediators (for example, IL-2 and IL-3). Acquired immunodeficiencies are well corrected by thymic factors if the genesis of immunodeficiency is due to thymic insufficiency and, as a result, immaturity of T-cells. However, thymus peptides do not correct other defects of T-lymphocytes (enzymatic, etc.).

Timalin - a complex of calf thymus peptides. Lyophilized powder in vials of 10 mg is dissolved in 1-2 ml of isotonic sodium chloride solution. Enter / m adults 5-20 mg (30-100 mg per course), children up to 1 g 1 mg; 4-6 years, 2-3 mg; 4-14 years - 3.5 mg for 3-10 days. Recommended for acute and chronic viral and bacterial infections, burns, ulcers, infectious bronchial asthma; diseases associated with immunodeficiency.

Taktivin - a complex of calf thymus polypeptides. Produced in vials of 1 ml - 0.01% solution. In chronic nonspecific lung diseases, the optimal dose of taktivin is 1-2 mcg / kg. The drug is administered in 1 ml (100 mcg) subcutaneously for 5 days, then 1 time per week for 1 month. In the future, 5-day monthly repeated courses are held. It is recommended for purulent-septic processes, lymphocytic leukemia, ophthalmic herpes, tumors, psoriasis, multiple sclerosis and diseases associated with immunodeficiency.

Timimulin - complex of bovine thymus polypeptides, administered intramuscularly at a dose of 1 mg per 1 kg of body weight for 7 days, then 2-3 times a week. This mode of administration was used in the treatment of combined forms of primary immunological deficiency. The best clinical effect is observed in patients with defects in the functional activity of cellular immunity effectors. Allergic reactions to the drug are possible.

Blood products and immunoglobulins Passive, replacement immunotherapy includes a group of methods based on the introduction of ready-made SI factors to the patient from the outside. Three types of human immunoglobulin preparations are used in clinical practice: native plasma, intramuscular immunoglobulin and intravenous immunoglobulin.

Autohemotransfusion serves as an alternative to allogeneic blood transfusion. During elective operations, it is recommended (Shander, 1999) to prepare autologous blood in advance with the introduction of erythropoietin once a week at a dose of 400 units/kg for 3 weeks, as well as recombinant leukopoiesis stimulators (GM-CSF), IL-11, which stimulates thrombocytopoiesis.

Leukocyte mass used as a means of replacement therapy in immunodeficiency states by the phagocytic system. The dose of leukomass is 3-5 ml per 1 kg of body weight.

stem cells - autologous and allogeneic, bone marrow and isolated from the blood, are able to restore the functions of organs and tissues due to differentiation into mature cells.

Native blood plasma (liquid, frozen) contains at least 6 g of total protein per 100 ml, incl. albumin 50% (40-45 g / l), alpha 1-globulin - 45%; alpha 2-globulin - 8.5% (9-10 g/l), beta-globulin 12% (11-12 g/l), gamma globulin - 18% (12-15 n/l). It may contain cytokines, ABO antigens, soluble receptors. Produced in bottles or plastic bags of 50-250 ml. Native plasma should be used on the day of its manufacture (no later than 2-3 hours after separation from the blood). Frozen plasma can be stored at -25°C or below for up to 90 days. At -10°C shelf life up to 30 days.

Plasma transfusion is carried out taking into account the compatibility of blood groups (ABO). At the beginning of the transfusion, it is necessary to conduct a biological test and, if signs of a reaction are found, stop the transfusion.

Dry (lyophilized) plasma due to a decrease in therapeutic usefulness due to the denaturation of some of the unstable protein components, a significant content of polymeric and aggregated IgG, high pyrogenicity, it is not advisable to use for immunotherapy of antibody deficiency syndromes.

Immunoglobulin human normal intramuscular The preparations are made from a mixture of more than 1000 blood sera of donors, due to which they contain a wide range of antibodies of different specificity, reflecting the state of collective immunity of the donor contingent. They are prescribed for the prevention of infectious diseases: hepatitis, measles, whooping cough, meningococcal infection, poliomyelitis. However, they are of little use for replacement therapy of antibody deficiency syndromes in primary and secondary immunodeficiencies. Most of the immunoglobulin is destroyed at the injection site, which, at best, can cause beneficial immunostimulation.

The production of hyperimmune intramuscular immunoglobulins, such as anti-staphylococcal, anti-influenza, anti-tetanus, anti-botulinum, used for specific immunotherapy, has been launched.

Intravenous immunoglobulins (IVG) safe in terms of transmission of viral infections, contain a sufficient amount of IgG3, responsible for the neutralization of viruses, the activity of the Fc fragment. Indications for use:

1. Diseases in which the effect of VIG is convincingly proven:

- Pprimary immunodeficiencies(X-linked agammaglobulinemia; common variable immunodeficiency; transient hypogammaglobulinemia of children; immunodeficiency with hyperglobulinemia M; deficiency of immunoglobulin G subclasses; deficiency of antibodies with normal levels of immunoglobulins; severe combined immunodeficiencies of all types; Wiskott-Aldrich syndrome; ataxia-telangiectasia; dwarfism with selectively short limbs; X-linked lymphoproliferative syndrome.

- secondary immunodeficiencies: hypogammaglobulinemia; prevention of infections in chronic lymphocytic leukemia; prevention of cytomegalovirus infection during allogeneic transplantation of bone marrow and other organs; rejection syndrome in allogeneic bone marrow transplantation; Kawasaki disease; AIDS in pediatric practice; Gilien Bare's disease; chronic demyelinating inflammatory polyneuropathy; acute and chronic immune thrombocytopenic purpura, including in children and associated with HIV infection; autoimmune neuropenia.

2. Diseases for which IVIG is likely to be effective: malignant neoplasms with deficiency of antibodies; prevention of infections in multiple myeloma; enteropathy, accompanied by protein loss and hypogammaglobulinemia; nephrotic syndrome with hypogammaglobulinemia; neonatal sepsis; severe myasthenia gravis; bullous pemphigoid; coagulopathy with the presence of an inhibitor to factor VIII; autoimmune hemolytic anemia; neonatal auto- or isoimmune thrombocytopenic purpura; post-infectious thrombocytopenic purpura; syndrome of anticardiolipin antibodies; multifocal neuropathies; hemolytic-uremic syndrome; systemic juvenile arthritis, spontaneous abortion (antiphospholipin syndrome); Schonlein-Genoch disease; severe IgA neuropathy; steroid-dependent bronchial asthma; chronic sinusitis; viral infections (Epstein-Barr, respiratory syncytial, parvo-, adeno-, cytomegalovirus, etc.); bacterial infections; multiple sclerosis; hemolytic anemia; viral gastritis; Evans syndrome.

4. Diseases for which VIG may be effective intractable convulsive seizures; systemic lupus erythematosus; dermatomyositis, eczema; rheumatoid arthritis, burn disease; Duchenne muscular atrophy; diabetes; thrombocytopenic purpura associated with the introduction of heparin; necrotizing enterocolitis; retinopathy; Crohn's disease; multiple trauma, recurrent otitis media; psoriasis; peritonitis; meningitis; meningoencephalitis

Features of the clinical application of VIG.

There are several options for the treatment and prophylactic use of immunoglobulins: replacement therapy for immunodeficiencies complicated by infection; immunotherapy of patients with severe infection (sepsis); suppressive IT in autoallergic and allergic diseases.

Hypogammaglobulinemia usually occurs in children with active bacterial infections. In such cases, immunotherapy should be carried out in saturation mode, simultaneously with active antimicrobial chemotherapy. Transfusion of native (fresh or cryopreserved) plasma is carried out in a single dose of 15-20 ml/kg of body weight.

GIG is administered at a daily dose of 400 mg/kg intravenously by drip or infusion at 1 ml/kg/hour to premature babies and 4-5 ml/kg/hour to full-term babies. Premature infants weighing less than 1500 g and IgG levels of 3 g/l and below VIG are administered to prevent infections. In immunodeficiencies with a low level of IgG in the blood, VIG is administered until the concentration of IgG in the blood is not lower than 4-6 g/l. In severe purulent-inflammatory diseases, they are administered daily 3-5 injections or every other day up to 1-2.5 g / kg. In the initial period, the intervals between injections can be 1-2 days, at the end up to 7 days. 4-5 injections are sufficient, so that in 2-3 weeks the patient receives an average of 60-80 ml of plasma or 0.8-1.0 g of GIG per 1 kg of body weight. For a month, no more than 100 ml of plasma or 1.2 g of VIG is transfused per 1 kg of the patient's body weight.

After relief of exacerbations of infectious manifestations in a child with hypogammaglobulinemia, as well as reaching levels of at least 400-600 mg / dL, you should switch to maintenance immunotherapy. Clinically effective preservation of the child out of exacerbation of foci of infection correlates with pre-transfusion levels above 200 mg / dl (correspondingly, the post-transfusion level on the next day after plasma transfusion is above 400 mg / dl). This requires a monthly administration of 15-20 ml/kg of native plasma weight or 0.3-0.4 g/kg of GIG. To obtain the best clinical effect, long-term and regular replacement therapy is necessary. For 3-6 months after the completion of the course of immunotherapy, a gradual increase in the completeness of the sanitation of foci of chronic infection is observed. This effect is maximally manifested for 6-12 months of continuous replacement immunotherapy.

Intraglobin - VIG contains 1 ml of 50 mg of IgG and about 2.5 mg of IgA, used for immunodeficiencies, infections, autoimmune diseases.

Pentaglobin - VIG enriched with IgM and contains: IgM - 6 mg, IgG - 38 mg, IgA - 6 mg per 1 ml. Used for sepsis, other infections, immunodeficiency: newborns 1 ml/kg/hour, 5 ml/kg daily - 3 days; adults 0.4 ml / kg / h, then 0.4 ml / kg / h, then continuously 0.2 ml / kg up to 15 ml / kg / h for 72 hours - 5 ml / kg 3 days, if necessary - repeat course.

Octagam - VIG contains 1 ml of 50 mg of plasma proteins, of which 95% IgG; less than 100 μg IgA, and less than 100 μg IgM. Close to native plasma IgG, all IgG subclasses are present. Indications congenital agammaglobulinemia, variable and combined immunodeficiencies, thrombocytopenic purpura, Kawasaki disease, bone marrow transplantation.

In case of immunodeficiency, it is administered up to the level of IgG in the blood plasma of 4-6 g/l. Initial dose 400-800 mg/kg followed by 200 mg/kg every 3 weeks. To achieve an IgG level of 6 g/l, 200-800 mg/kg per month must be administered. For control, the level of IgG in the blood is determined.

For the treatment and prevention of infections, doses of VIG depend on the type of infection. As a rule, it is administered as early as possible. For cytomegalovirus (CMV) infection, the dose should be 500 mg/kg weekly for 12 weeks because the elimination half-life of the IgG3 subclass responsible for neutralizing the virus is 7 days, and clinical infection appears between 4-12 weeks post-infection. At the same time, synergistically acting antiviral drugs are prescribed.

To prevent neonatal sepsis in premature infants weighing 500 to 1750 grams, it is recommended to administer 500 to 900 mg/kg/day of IgG to maintain its concentration of at least 800 mg/kg under the control of IgG levels in the blood. The increase in IgG levels persists for an average of 8-11 days after administration. The introduction of IgG to pregnant women after 32 weeks reduced the risk of infection in newborns.

VIG preparations are also used to treat sepsis, especially in combination with antibiotics. The recommended blood level is over 800 mg/kg.

After allogeneic bone marrow transplantation for the prevention of CMV and other infections, IVIG is administered weekly for 3 months, and then 500 mg/kg every 3 weeks for 9 months.

In the treatment of autoimmune diseases, doses are 250-1000 mg/kg for 2-5 days every 3 weeks. Children with autoimmune thrombocytopenic purpura are administered 400 mg / kg for 2 days, adults - 1 g / kg for 2 or 5 days.

The mechanism of action of immunoglobulins depends on the stateFcleukocyte receptors: by binding to them, immunoglobulins enhance their functions during infection, and, conversely, inhibit them during allergies.

Anti-rhesus immunoglobulin inhibits the synthesis of antibodies against a Rh-positive fetus in a Rh-negative woman by the type of feedback.

Mechanism of actionIgGconsists of specific and non-specific effects. Specific is associated with the action of a small amount of always present antibodies. Nonspecific - with an immunomodulatory effect. Both effects are usually mediated throughFcleukocyte receptors. ContactingFc-receptors of leukocytes, immunoglobulins activate them, in particular phagocytosis. If there are antibodies among the immunoglobulin molecules, they can opsonize bacteria or neutralize viruses.

Novikov D.K. and Novikov V.I. (2004) developed a method for predicting the effectiveness of immunoglobulin preparations. It was found that the therapeutic effect of immunoglobulin preparations depended on the presence of Fc receptors on the patients' leukocytes. The method consists in determining the number of leukocytes carrying receptors for Fc fragments of immunoglobulins and the ability of leukocytes to be sensitized by antistaphylococcal immunopreparations in the blood of patients before treatment. In the presence of 8% or more of lymphocytes and 10% or more of granulocytes in an amount of more than 100 in 1 μl of blood with Fc receptors, and a positive reaction to the transfer of sensitization, the effectiveness of immunotherapy is predicted.

The results of the immunodrug transfer of sensitization to lymphocytes are evaluated in a leukocyte migration suppression test using antigens corresponding to antibodies in the antiserum, for example, staphylococcus antigens. If staphylococcal antigens inhibit the migration of leukocytes treated with anti-staphylococcal plasma, but do not inhibit the migration of leukocytes treated with normal plasma, the reaction is considered positive.

The proposed method makes it possible to predict the effectiveness of both specific (when using immune preparations) and non-specific (by Fc receptors) immunotherapy with immunoglobulins.

Monoclonal antibodies mice against human lymphocytes and cytokines are used to suppress autoimmune reactions, transplantation immunity. Some of the uses for monoclonal antibodies are listed below:

Antibodies against CD20 B-lymphocytes for immunosuppression ( Mabthera )

Antibodies against receptors for interleukin 2 - with the threat of rejection of the kidney allograft;

Antibodies against IgE - in severe allergic reactions ( Xolair ).

Bone marrow, leukocyte and spleen preparations

Myelopid obtained from a culture of porcine bone marrow cells. It contains immuno-modulators of bone marrow origin - myelopeptides. Myelopid stimulates antitumor immunity, phagocytosis, antibody-producing cells, proliferation of granulocytes and macrophages in the bone marrow. Myelopid is used in the treatment of septic, protracted and chronic infectious diseases of a bacterial nature, secondary immunodeficiencies, since it has the ability to enhance the synthesis of antibodies in the presence of antigens. Myelopid (5 mg bottle) is administered intramuscularly daily or every other day. Single dose 0.04-0.06 mg/kg. The course of therapy consists of 3-10 injections performed every other day.

Leukocyte transfer factor("transfer factor") a group of biologically active substances extracted from leukocytes of healthy or immunized donors with the help of repeated consecutive freezing and thawing. Transfer factors increase delayed-type hypersensitivity to specific antigens. The drug prevents the development of immunological tolerance, enhances the differentiation of T-cells, neutrophil chemotaxis, the formation of interferons, the synthesis of immunoglobulins (mainly class M). A single dose for adults is 1-3 dry matter units. It is used in the treatment of primary immunodeficiencies, especially of the macrophage type and in the treatment of secondary immunodeficiencies of the lymphoid type (with defects in differentiation and proliferation of T-cells, impaired chemotaxis and antigen presentation).

Cytokines- a group of biologically active glycopeptide mediators secreted by immunocompetent cells, as well as fibroblasts, endothelial and epithelial cells. The main directions of cytokine therapy:

Inhibition of the production of inflammatory cytokines (IL-1, TNF-α) with anti-inflammatory drugs and monoclonal antibodies;

Correction of immunoreactivity deficiency by cytokines (drugs IL-2, IL-1, interferons);

Enhancement of the immunostimulating effect of vaccines by cytokines;

Stimulation of antitumor immunity by cytokines.

Betaleukin - recombinant IL-lβ, available in 0.001 ampoules; 0.005 or 0.0005 mg (5 ampoules). Stimulates leukopoiesis in leukopenia caused by cytostatics and radiation, differentiation of immunocompetent cells. It is used in oncology, with postoperative complications, protracted, purulent-septic infections. Administered intravenously at a dose of 5 ng/kg for immunostimulation; 15-20 ng/kg to stimulate leukopoiesis daily with 500 ml of 0.9% sodium chloride solution for 1-2 hours. The course is 5 infusions.

Roncoleukin - recombinant IL-2. Indications: signs of immunodeficiency, purulent-inflammatory diseases, sepsis, peritonitis, abscesses and phlegmon, pyoderma, tuberculosis, hepatitis, AIDS, oncological diseases. With sepsis, 0.25 - 1 mg (25,000 - 1,000,000 ME) are administered in 400 ml of a 0.9% solution of sodium chloride in / in drip at a rate of 1-2 ml / min for 4-6 hours, for oncological diseases - 1-2 million IU 2-5 times at intervals of 1-3 days, 25,000 IU in 5 ml of saline is administered for sinusitis in the maxillary or frontal sinuses; installations in the urethra for chlamydia daily at 50,000 ME (14-20 days); orally for yersineosis and diarrhea, 500,000 - 2,500,000 in 15-30 ml of distilled water on an empty stomach daily for 2-3 days. Ampoules of 0.5 mg (500,000 IU), 1 mg (1,000,000 IU).

Neupogen (filgrastim) - recombinant granulocyte colony-stimulating factor (G-CSF) stimulates the formation of functionally active neutrophils and partially monocytes already in the first 24 hours after administration, activates hematopoiesis (for autologous blood and bone marrow sampling for transplantation). Applied with chemotherapeutic neutropenia, for the prevention of infections at a dose of 5 mcg / kg / day in / in or s / c 24 hours after the treatment cycle for 10-14 days In congenital neutropenia 12 mcg / kg per day s / c daily.

Leucomax (molgramostim) - recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). Used for leukopenia at a dose of 1-10 mcg / kg / day, subcutaneously according to indications.

Granocyte (Lenograstim) - granulocyte colony-stimulating factor, stimulates the proliferation of granulocyte precursors, neutrophils. Used for neutropenia, 2-10 mcg / kg / day for 6 days.

Leukinferon - is a complex of cytokines of the first phase of the immune response and includes IFN-α, IL-1, IL-6, IL-12, TNF-α, MIF. In case of bacterial infections, the course of treatment should be intensive (every other day, one amp., / m) and only with the restoration of immunity, supportive (2 times a week, 1 amp., / m).

Interferons The classification of interferons according to their origin is presented in Table 1.

Table 1. Classification of interferons

The mechanism of the immunomodulatory action of interferons is realized through increased expression of receptors on cell membranes and through involvement in differentiation. They activate NK, macrophages, granulocytes, inhibit tumor cells. The effects of different interferons are different. Type I interferons - α and β - stimulate expression on class I MHC cells, and also activate macrophages and fibroblasts. Type II interferon-gamma enhances macrophage function, MHC class II expression, cytotoxicity of NK and T-killers. The biological significance of interferons is not limited to a pronounced antiviral effect, they exhibit antibacterial and immunomodulatory activity.

The interferon status of an immunocompetent person is normally determined by trace amounts of these glycoproteins in the blood (< 4 МЕ/мл) и на слизистых оболочках, но лейкоциты здоровых людей при антигенном раздражении обладают выраженной способностью синтезировать интерфероны. При хронических вирусных заболеваниях (герпес, гепатит и др.) способность к выработке интерферонов у больных снижена. Наблюдается синдром дефецита интерферона. В то же время у детей в случаях первичных иммунодефицитов лимфоидного типа интерферонная функция лейкоцитов сохранена. При антигенном стимуле в норме вырабатываются все типы интерферонов, однако наибольшее значение для местного противовирусного иммунного статуса имеет титр α-интерферона.

Interferons in doses up to 2 millionMEhave an immunostimulating effect, and their high doses (10 millionME) cause immunosuppression.

It must be remembered that all interferon preparations can cause fever, flu-like syndrome, neutropenia and thrombocytopenia, alopecia, dermatitis, impaired liver and kidney function, and a number of other complications.

Leukocyte α-interferon (egiferon, valferon) used as a prophylactic drug in the form of local applications on the mucous membrane during epidemic periods and in the treatment of early stages of acute respiratory and other viral diseases. With viral rhinitis, it is necessary to administer intranasally a sufficiently large dose (3x10 b ME) 3 times a day in the early period of the disease. The drug is rapidly excreted by mucus and inactivated by its enzymes. Using it for more than a week can cause increased inflammation. Interferon eye drops are used for viral eye infections.

Interferon-β (betaferon) used to treat multiple sclerosis, inhibits the replication of viruses in the brain tissue, activates suppressors of the immune response.

Human immune γ-interferon (gammaferon) has cytotoxic effects, modulates the activity of T-lymphocytes and activates B-cells. In this case, the drug can cause inhibition of antibody production, phagocytosis and modify the response of lymphocytes. The effect of γ-interferon on T cells persists for 4 weeks. Used for psoriasis, HIV infection, atopic dermatitis, tumors.

Doses of interferon preparations for parenteral administration are selected individually: from several thousand units per 1 kg of body weight to several million units per 1 injection. Course 3-10 injections. Adverse reactions: flu-like syndrome.

Recombinant interferon alfa-2β (intron A) prescribed for the following diseases:

multiple myeloma- p / c 3 p. per week, 2 x10 5 IU / m 2.

Kaloshi's sarcoma- 50 x 10 5 IU/m 2 subcutaneously daily for 5 days, followed by a break of 9 days, after which the course is repeated;

malignant melanoma- 10 x 10 6 IU s / c 3 times a week every other day for at least 2 months;

hairy cell leukemia- p / c 2 x 10 b IU / m 2 3 p. per week 1-2 months;

papillomatosis, viral hepatitis- the initial dose of 3 x 10 b IU / m 3 times a week for 6 months in the first case (after surgical removal of papillomas) and 3-4 months - in the second case.

Laferon (laferobiot) recombinant alpha-2beta interferon is used in the treatment of adults and children with: acute and chronic viral hepatitis; acute viral and viral-bacterial diseases, rhino- and coronavirus, parainfluenza infections, SARS; with meningoencephalitis; with herpetic diseases: shingles, lesions of the skin, genitals, keratitis; acute and chronic septic diseases (sepsis, septicemia, osteomyelitis, destructive pneumonia, purulent mediastinitis); multiple sclerosis (injections for at least one year); cancer of the kidneys, breast, ovary, bladder, melanoma (including in the form of disimination); hemoblastosis: hairy cell leukemia; chronic myeloid leukemia, acute lymphoblastic leukemia, lymphoblastic lymphosarcoma, T-cell lymphoma, multiple myeloma, Kaposi's sarcoma; as a remedy that relieves intoxication during irradiation and chemotherapy of cancer patients. Laferon is produced for: 100 thousand IU, 1 million IU, 3 million IU, 5 million IU, 6 million IU, 9 million IU and 18 million IU. Assign when: herpes zoster chip along the nerve near the rash 2-3 million IU in 5 ml of physical. solution and application to the papules of laferon mixed with cosmetic emulsion LA-KOS (or baby cream) in a ratio of 1 million IU of laferon per 1-2 cm 3 of cream; acute viral hepatitis B i / m 1 - 2 million IU 2 p. per day for 10 days; X chronic viral hepatitis B i / m 5 million IU 3 r. per week for 4-6 weeks (in case of a hyperthermic reaction, 20-30 minutes before the administration of laferon, take 0.5 g of paracetamol, if necessary, repeat the intake of antipyretics 2-3 hours after the injection of laferon); at x chronic viral hepatitis C i / m at a dose of 3 million IU 3 r. per week for 6 months; with SARS and influenza : i / m 1-2 million IU 1-2 p. per day, together with intranasal administration (1 million IU diluted in 5 ml of physical solution, poured into each nasal passage 0.4-0.5 ml 3-6 times a day, warmed up to 30- 35°C); with post-influenza meningoencephalitis inject / in 2-3 million IU 2 r. per day (under the protection of antipyretics); with sepsis i / m (drip on saline) administration at a dose of 5 million IU for 5 days or more; at d isplasia of the epithelium of the cervix, papilloma of viral and herpetic genesis, with chlamydia IM 3 million IU for 10 days and locally: mix 1 million IU of laferon with 3-5 cm 3 of LA-KOS cosmetic emulsion (or baby cream), apply with an applicator to the cervix every day (preferably before bedtime); at k eratitis, keratoconjunctivitis, keratouveitis parabulbarno at 0.25-0.5 million IU for 3-10 days and laferon instillations: 250-500 thousand IU per 1 ml of physical. solution 8-10 times a day; with warts IM 1 million IU for 30 days; with multiple sclerosis IM 1 million IU 2-3 times a day for 10 days, then 1 million IU 2-3 times a week for 6 months; with cancer of various localizations i / m 3 million IU 5 days before surgery, then courses of 3 million IU 10 days after 1.5-2 months; with primary limited melanoblastoma endolymphatic administration of 6 million IU / m 2 in combination with cytostatics, maintenance therapy with weekly courses: 2 million IU / m 2 of laferon every other day, 4 times (course - 8 million IU / m 2) monthly; with multiple myeloma - i / m daily at a dose of 7 million IU / m 2 for 10 days (course - 70 million IU / m 2) after a course of chemotherapy and gamma therapy, maintenance therapy with weekly courses at a dose of 2 million IU / m 2 in / m, 4 injections every other day (course - 8 million IU / m 2), for 6 months, the interval between courses is 4 weeks; With Arkoma Kaposi i / m 3 million IU / m 2 10 days after cytostatic therapy, maintenance therapy with weekly courses, s / c 2 million IU / m 2 4 times a day (course - 8 million IU / m 2), 6 courses with an interval of 4 weeks; b azal cell carcinoma s / c injection into the tumor zone of 3 million IU in 1-2 ml of water for injection, 10 days, a second course after 5-6 weeks.

Roferon-A - recombinant interferon - alpha 2a is administered intramuscularly (up to 36 million IU) or s / c (up to 18 million IU). With hairy cell leukemia - 3 million IU / day / m 16-24 weeks; multiple myeloma - 3 million IU 3 times a week / m; Kaloshi's sarcoma and renal cell carcinoma - 18-36 million IU per day; viral hepatitis B - 4.5 million IU intramuscularly 3 times a week for 6 months.

Viferon - recombinant interferon alpha-2β is used in the form of suppositories (150 thousand IU, 500 thousand IU, 1 million IU), ointment (40 thousand IU per 1 g). It is prescribed for infectious and inflammatory diseases (ARVI, pneumonia, meningitis, sepsis, etc.), for hepatitis, for herpes of the skin and mucous membranes - 1 time per day or every other day in candles; with herpes - additionally lubricate the affected skin with ointment 2-3 times a day. Candles for children 150 thousand ME 3 times a day after 8 hours 5 days. With hepatitis - 500 thousand IU each.

Reaferon (interal) recombinant interferon α2 is prescribed for hepatitis B, viral meningoencephalitis IM 1-2x10 b IU 2 times a day for 5-10 days, then the dose is reduced. For influenza, measles, intranasal-Co can be used; with genital herpes - ointment (0.5x10 b IU / g), herpes zoster - intramuscularly at 1x10 6 IU per day for 3-10 days. Also used to treat tumors.

Biostimulants of various origins Many signals connecting the CNS and the immune system are transmitted by biologically active substances that perform the functions of neurotransmitters and neuromodulators in the CNS, and the functions of hormones in peripheral tissues. These include: hormones, biogenic amines and peptides. Neuro-regulatory biological mediators and hormones affect the differentiation of lymphocytes and their functional activity. For example, the adenohypophysis secretes such immunotropic mediators as somatotropin, adrenocorticotropic hormone, gonadotropic hormones, a group of thyroid-stimulating hormones, as well as a special hormone - thymocyte growth factor.

Heparin - mucopolysaccharide with M.M. 16-20 KDa, stimulates hematopoiesis, enhances the release of leukocytes from the bone marrow depot and increases the functional activity of cells, enhances the proliferation of lymphocytes in the lymph nodes, increases the resistance of peripheral blood erythrocytes to hemolysis. In doses of 5-10 thousand units, it has a fibrinolytic, platelet-disaggregating and weak immunosuppressive effect, enhances the effect of steroids and cytostatics. When administered intradermally in patients at several points in small doses from 200 to 500 IU, it has an immunoregulatory effect - it normalizes the reduced level of lymphocytes, their subpopulation spectrum; has a stimulating effect on neutrophils.

vitamins Under the influence of vitamins, the activity of biochemical processes in cells, including immunological ones, changes. Some forms of immunological deficiency are associated with a deficiency of certain vitamins. An example would be the primary form of a phagocytosis defect - Chediak-Higashi syndrome. With echo disease, taking vitamin C at a dose of 1 gram per day for several weeks activates the enzymatic redox systems of phagocytes (neutrophils and macrophages) to the stage of compensation for their bactericidal function.

Vitamin C normalizes the activity of T-lymphocytes and neutrophils in patients with initially reduced levels. However, high doses (10 g) cause immunosuppression.

Vitamin E - (tocopherol acetate, α-tocopherol) found in sunflower, corn, soybean, sea buckthorn oil, eggs, milk, meat. It has antioxidant and immunostimulating properties, is used for muscular dystrophy, sexual dysfunction, and chemotherapy. Assign inside and intramuscularly at 0.05-0.1 g per day for 1-2 months. The appointment of vitamin E in a daily dose of 300 IU for 6-7 days orally increases the number of leukocytes, T- and B-lymphocytes. In combination with selenium, vitamin E increased the number of antibody-forming cells. It is believed that vitamin E changes the activity of lipo- and cyclooxygenases, enhances the production of IL-2 and immunity, and inhibits tumor growth. Tocopherol at a dose of 500 mg daily normalized the immune status.

Zinc acetate (10 mg 2 times a day, 5 mg up to 1 month) is a stimulant of antibody genesis and delayed-type hypersensitivity. Zinc thymulin is considered one of the main thymus hormones. Zinc preparations increase resistance to respiratory infections. With a deficiency of this microelement, a quantitative deficiency of antibody-producing cells, defects in the synthesis of the IgG 2 and IgA subclass are determined. A separate form of primary immunological insufficiency is described - "enteropathic acrodermatitis with combined immunological insufficiency", which is almost entirely corrected by taking zinc preparations, for example, zinc sulfate. The drug is taken continuously. Zinc oxide is prescribed in powder after meals with milk, juices. With acrodermatitis - 200-400 mg per day, then 50 mg / day. Children, infants 10-15 mg / day, adolescents and adults - 15-20 mg / day. Prophylactically - 0.15 mg / kg / day.

Lithium has an immunotropic effect. Lithium chloride at a dose of 100 mg/kg or lithium carbonate at an age dose per dose cause an immunomodulatory effect in immunological insufficiency caused by a deficiency of this microelement. Lithium enhances granulocytopoiesis, the production of colony-stimulating factor by bone marrow cells, which is used in the treatment of hypoplastic hematopoietic conditions, neutropenia and lymphopenia. Activates phagocytosis. Seme of the drug: the dose is gradually increased from 100 mg to 800 mg / day, and then reduced to the original.

Phytoimmunomodulators Infusions, decoctions of herbs have immunomodulating (immunostimulating) activity.

Eleutherococcus with a normal immune status does not change the parameters of immunity. It has interferonogenic activity. With a deficiency in the number of T-cells, it normalizes indicators, enhances the functional activity of T-cells, activates phagocytosis, non-specific immune responses. Apply 2 ml of alcohol extract 30 minutes before meals 3 times a day for 3-4 weeks. In children, for the prevention of recurrence of acute respiratory infections, 1 drop / 1 year of life 1-3 times a day for 3-4 weeks.

Ginseng It increases the efficiency and overall resistance of the body to diseases and adverse effects, does not cause harmful side effects and can be used for a long time. Ginseng root is a strong stimulant of the central nervous system, does not have negative effects, does not disturb sleep. Ginseng preparations stimulate tissue respiration, increase gas exchange, improve blood composition, normalize heart rhythm, increase eye photosensitivity, accelerate healing processes, suppress the vital activity of some bacteria, and increase resistance to radiation. Preparations from it are recommended to be used in the autumn-winter period. The most stimulating effect is observed when using ginseng powder and 40 degree alcohol tincture. A single dosage is 15-25 drops of alcohol tincture (1:10) or 0.15-0.3 g of ginseng powder. Take 2-3 times a day before meals in courses of 30-40 days, then take a break.

Infusion of chamomile inflorescences Contains essential oils, azulene, anti-thymysic acid, heteropolysaccharides with immunostimulatory properties. Chamomile infusion is used to increase the activity of the immune system after hypothermia, during prolonged stressful situations, in the autumn-spring period to prevent colds. The infusion is taken orally 30-50 ml 3 times a day for 5-15 days.

Echinacea ( Echinacea purpurea ) has an immunostimulating, anti-inflammatory effect, activates macrophages, secretion of cytokines, interferons, stimulates T-cells. It is used for the prevention of colds in the autumn-spring period, as well as for the treatment of viral and bacterial infections of the upper respiratory tract, urinary tract, etc. Recommended 40 drops 3 times a day, diluted with water. Maintenance doses - 20 drops 3 times a day orally for 8 weeks.

Immunal - infusion of 80% Echinacea purpurea juice, 20% ethanol. Assign 20 drops inside every 2-3 hours for acute respiratory infections, influenza, then 3 times a day. Course 1-8 weeks.

Biostimulants - adaptagens: tincture of lemongrass, decoctions and infusions of string, celandine, calendula, tricolor violet, licorice root and dandelion have an immunocorrective effect. There are drugs: glyceram, liquiriton, breast elixir, caleflon, calendula tincture.

Bacterioimmunotherapy Mucosal dysbioses play an important role in pathology. Antibiotic therapy, cytostatic and radiation therapy cause a violation of the biocenosis of the mucous membranes, primarily the intestines, and then dysbacteriosis occurs. Probiotic lactobacilli and bifidobacteria, colibacilli, releasing colicins, inhibit the growth of pathogenic bacteria. However, it is important not only the suppression of pathogenic bacteria and fungi, but also the fact that during dysbiosis there is a deficiency of the necessary biologically active substances produced by the normal flora: vitamins (B 12 , folic acid), Escherichia coli lipopolysaccharides that stimulate the activity of the immune system, etc. As a result, dysbiosis is accompanied by immunodeficiency. Therefore, preparations of natural flora are used to restore normal intestinal biocenosis, which plays an important role in stimulating the functions of the immune system.

Gram-positive lactobacilli and bifidobacteria stimulate anti-infectious and antitumor immunity, induce tolerance in allergic reactions. They directly cause a moderate release of cytokines by immunocompetent cells. As a result, the synthesis of secretory IgA is enhanced. On the other hand, lactobacilli, penetrating through the mucous membrane, can cause infection and induce a systemic immune response, so probiotic bacteria serve as strong immunomodulators, especially in an immunodeficient organism. Preparations of live bacteria are not used simultaneously with antibiotics and chemotherapy drugs that inhibit their growth.

Lactobacilli - antagonists of pathogenic microbes, secrete enzymes and vitamins. It is recommended to prescribe together with specific bacteriophages that suppress pathogenic flora. It is not advisable to use them for candidiasis, since their acids enhance the growth of fungi.

Bifidumbacterin dry - dried live bifidobacteria. Adults: 5 tablets 2-3 times a day 20 minutes before meals. Course up to 1 month. Children - in vials, diluted with warm boiled water (1 tablet: 1 teaspoon) 1-2 doses 2 times a day.

It is used for dysbacteriosis, enteropathy, artificial feeding of children, treatment of premature, acute intestinal infections (dysentery, salmonellosis, etc.), chronic intestinal diseases (gastritis, duodenitis, colitis), radiation and chemotherapy of tumors, candidal vaginitis, food intolerance and food allergies, dermatitis, eczema, normalization of the microflora of the oral mucosa in stomatitis, periodontitis, diabetes mellitus, chronic diseases of the liver and pancreas, work in harmful and extreme conditions.

Bificol dry - live dried bifidobacteria and E. coli vrt7. Adults and children over 3 years old - 20-30 minutes before meals, 3-5 tablets 2 times a day, drink water. Course 2-6 weeks.

Bifiform contains at least 10 7 Bifidobacterium lobgum, and also 10 7 En-fgrococcus faecium in capsules. With dysbacteriosis of I-II degree, 1 capsule 3 times a day, a course of 10 days, with dysbacteriosis of II-III degree, an increase in the course to 2-2.5 weeks

Linex - combined preparation, contains three components of natural microflora from different parts of the intestine: in one capsule - 1.2x10 7 live lyophilized bacteria Bifidobacterium infantis, Lactobacillus, Cl. dophilus and str. faecium resistant to antibiotics and chemotherapy. Maintain microbiocenosis in all parts of the intestine - from the small intestine to the rectum. Assign: adults 2 capsules 3 times a day with boiled water, milk; children under 2 years old - 1 capsule 3 times a day, drinking liquid or mixing the contents of the capsule with it.

Colibacterin dry - dried live Escherichia coli, strain M-l7, which is an antagonist for pathogenic microbes, stimulates the immune system, as well as enzymes and vitamins. Adults 3-5 tablets 2 times a day 30-40 minutes before meals, washed down with alkaline mineral water. Course 3 weeks -1.5 months.

Bifikol - combination drug.

Baktisubtil - sporobacteria culture GR-5832 (ATSS 14893) 35 mg-10 9 spores, used for diarrhea, dysbiosis, 1 cap 3-10 times a day 1 hour before meals.

Enterol-250 , unlike bacterio-containing preparations, it contains yeast-saccharomycetes (Saccharomycetes boulardii), which serve as antagonists of pathogenic bacteria and fungi. Recommended for diarrhea, dysbacteriosis, can be used in combination with antibiotic therapy. Assign to children under 3 years old 1 capsule 1-2 times a day for 5 days, children over 3 years old and adults 1 capsule 2 times a day for 7-10 days.

Hilak forte contains products of metabolic activity of probiotic strains of lactobacilli and normal intestinal microorganisms - Escherichia coli and fecal streptococcus: lactic acid, amino acids, short-chain fatty acids, lactose. Compatible with antibiotics. The simultaneous use of antacids is not recommended due to the possible neutralization of lactic acid, which is part of Hilak-forte. Assign in a dose of 20-40 drops 3 times a day for 2-3 weeks (infants 15-30 drops 3 times a day), taken in a small amount of liquid before or during meals, excluding milk and dairy products.

Gastrofarm - live lyophilized cells Lactobacillus bulgaricus 51 and metabolites of their vital activity (lactic and malic acids, nucleic acids, a number of amino acids, polypeptides, polysaccharides). Inside, 3 times a day, chewing with a small amount of water. A single dose for children is S tablets, for adults - 1-2 tablets.

Immunomodulatory effects of antibiotics Conditionally pathogenic microbes (staphylococci, streptococci, Escherichia coli, etc.) are etiological factors and also pathogens of most diseases that have an infectious and inflammatory nature. Therefore, the main therapeutic measure is antibacterial therapy, in particular, the use of antibiotics. Attempts to "sterilize" the patient with antibacterial agents lead to dysbacteriosis, mycoses, which create new problems.

Opportunistic microbes do not cause disease in most people and are normal inhabitants of the skin and mucous membranes. The reason for their activation is insufficient resistance of the organism - immunodeficiency. Therefore, the basis of infectious and inflammatory diseases are congenital or acquired, acute and chronic immunodeficiencies, which create favorable conditions for the reproduction of microbes that are normally constantly eliminated by immunity factors. An example of a widespread acute immunodeficiency is the cold syndrome, when, against the background of hypothermia, the body's natural resistance to opportunistic microbes is suppressed.

From what has been said, it follows that without restoring the reactivity of the organism, the suppression of microflora alone is often insufficient for a complete recovery. Moreover, many antibacterial agents suppress the immune system, create conditions for contamination of the body with antibiotic-resistant strains. The problem is further exacerbated by the widespread “prophylactic” use of antibacterial agents for viral infections. The main ways to solve the problem: the simultaneous use of antibiotics and drugs that normalize the oppressed links of the immune system; additional use of immunorehabilitation means; maximum preservation and restoration of the body's endoecology. Two types of influence of antibiotics on the immune response are possible: those associated with the lysis or damage of bacteria and due to a direct effect on the cells of the immune system.

1. Effects mediated by damaged bacteria:

- inhibition of cell wall synthesis (penicillins, clindacimin, cephalosporins, carbapenems, etc.) - reduces the resistance of bacterial cells to the action of bactericidal factors of leukocytes and macrophages;

inhibition of protein synthesis (macrolides, rifampicin, tetracyclines, fluoroquinolones, etc.) causes changes in the cell membrane of microorganisms and can enhance phagocytosis by reducing the expression of proteins with antiphagocytic functions on the surface of bacterial cells, at the same time, these antibiotics suppress the immune response due to impaired protein synthesis in the cells of the immune system;

disintegration of the membrane of gram-negative bacteria and an increase in its permeability (aminoglycosides, polymyxin B) increases the sensitivity of microorganisms to the action of bactericidal factors.

2. The effects of antibiotics due to the release from microorganisms during their destruction of biologically active substances: endotoxins, exotoxins, glycopeptides, etc. Small doses of endotoxins are necessary for the normal development of immunity, have a beneficial effect, stimulate nonspecific resistance to bacterial and viral infections, as well as to cancer. This can be seen in the example of Escherichia coli, which is a normal inhabitant of the intestine. When it is destroyed, a small amount of endotoxin is released, which stimulates local and general immunity. Therefore, in such protracted infections, bacterial lipopolysaccharide preparations - prodigiosan, pyrogenal and licopid - are often effective. However, with severe infection and the release of a large amount of endotoxin into the bloodstream, the cytokines induced by it (IL-1, TNF-α) can cause inhibition of phagocytosis, severe toxicosis up to toxic-septic shock with a drop in cardiovascular activity. On the other hand, extensive lysis of large numbers of bacteria and release of endotoxins can lead to adverse reactions such as Jarish-Herxheimer.

Effects due to the direct influence of antibiotics on the immune system:

Beta-lactam antibiotics enhance phagocytosis and leukocyte chemotaxis, but in high doses they can inhibit antibody formation and bactericidal blood;

Cephalosporins, by binding to neutrophils, increase their bactericidal activity, chemotaxis and oxidative metabolism in patients with immunodeficiencies.

Gentamicin reduces phagocytosis and chemotaxis of granulocytes and RBTL.

macrolides (erythromycin, roxithromycin and azithromycin) stimulate the functions of phagocytes, bactericidal activity, chemotaxis, synthesis of cytokines (IL-1, etc.).

Fluoroquinolones enhance the proliferation of cells of the immune system, increase the synthesis of IL-2, phagocytosis and bactericidal activity.

tetracycline, doxycycline inhibit phagocytes and antibody synthesis.

The immunomodulatory effects of antibiotics on the immune system lead to the development of allergic reactions. The basis is the interaction of antibiotics as haptens with the cells of the immune system and the activation of a specific immune response.

Immunomodulators are a group of pharmacological drugs that activate the body's immunological defenses at the cellular or humoral level. These drugs stimulate the immune system and increase the body's nonspecific resistance.

major organs of the human immune system

Immunity is a unique system of the human body that can destroy foreign substances and needs proper correction. Normally, immunocompetent cells are produced in response to the introduction of pathogenic biological agents into the body - viruses, microbes and other infectious agents. Immunodeficiency states are characterized by reduced production of these cells and are manifested by frequent morbidity. Immunomodulators are special preparations, united by a common name and a similar mechanism of action, used to prevent various ailments and strengthen the immune system.

Currently, the pharmacological industry produces a huge number of drugs that have immunostimulating, immunomodulatory, immunocorrective and immunosuppressive effects. They are freely sold in the pharmacy chain. Most of them have side effects and have a negative effect on the body. Before purchasing such medicines, you should consult with your doctor.

• Immunostimulants strengthen human immunity, ensure more efficient functioning of the immune system and provoke the production of protective cellular links. Immunostimulants are harmless to people who do not have immune system disorders and exacerbations of chronic pathologies.
• Immunomodulators correct the balance of immunocompetent cells in autoimmune diseases and balance all components of the immune system, suppressing or increasing their activity.
• Immunocorrectors affect only certain structures of the immune system, normalizing their activity.
• Immunosuppressants suppress the production of immunity links in cases where its hyperactivity harms the human body.

Self-medication and inadequate intake of drugs can lead to the development of autoimmune pathology, while the body begins to perceive its own cells as foreign and fight them. Immunostimulants should be taken according to strict indications and as prescribed by the attending physician. This is especially true for children, because their immune system is fully formed only by the age of 14.

But in some cases, it is simply impossible to do without taking drugs of this group. In severe diseases with a high risk of developing serious complications, taking immunostimulants is justified even in babies and pregnant women. Most immunomodulators are low-toxic and quite effective.

The use of immunostimulants

Preliminary immunocorrection is aimed at eliminating the underlying pathology without the use of basic therapy drugs. It is prescribed to persons with diseases of the kidneys, digestive system, rheumatism, in preparation for surgical interventions.

Diseases in which immunostimulants are used:

1. congenital immunodeficiency,
2. malignant neoplasms,
3. Inflammation of viral and bacterial etiology,
4. Mycoses and protozooses,
5. Helminthiasis,
6. Renal and hepatic pathology,
7. Endocrine pathology - diabetes mellitus and other metabolic disorders,
8. Immunosuppression against the background of taking certain drugs - cytostatics, glucocorticosteroids, NSAIDs, antibiotics, antidepressants, anticoagulants,
9. Immunodeficiency due to ionizing radiation, excessive alcohol intake, severe stress,
10. Allergy,
11. Conditions after transplantation,
12. Secondary post-traumatic and post-intoxication immunodeficiency states.

The presence of signs of immune deficiency is an absolute indication for the use of immunostimulants in children. The best immunomodulator for children can only be selected by a pediatrician.

People who are most often prescribed immunomodulators:

• Children with weak immunity
• Elderly people with depleted immune systems
• People with busy lifestyles.

Treatment with immunomodulators should be under the supervision of a physician and an immunological blood test.

Classification

The list of modern immunomodulators today is very large. Depending on the origin, immunostimulants are isolated:

Self-administration of immunostimulants is rarely justified. Usually they are used as an adjunct to the main treatment of pathology. The choice of drug is determined by the characteristics of immunological disorders in the patient's body. The effectiveness of drugs is considered maximum during an exacerbation of the pathology. The duration of therapy usually varies from 1 to 9 months. The use of adequate doses of the drug and proper adherence to the treatment regimen allows immunostimulants to fully realize their therapeutic effects.

Some probiotics, cytostatics, hormones, vitamins, antibacterial drugs, immunoglobulins also have an immunomodulatory effect.

Synthetic immunostimulants

Synthetic adaptogens have an immunostimulatory effect on the body and increase its resistance to adverse factors. The main representatives of this group are "Dibazol" and "Bemitil". Due to the pronounced immunostimulating activity, the drugs have an anti-asthenic effect and help the body recover quickly after a long stay in extreme conditions.

With frequent and protracted infections, for prophylactic and therapeutic purposes, Dibazol is combined with Levamisole or Decamevit.

Endogenous immunostimulants

This group includes preparations of thymus, red bone marrow and placenta.

Thymic peptides are produced by thymus cells and regulate the immune system. They change the functions of T-lymphocytes and restore the balance of their subpopulations. After the use of endogenous immunostimulants, the number of cells in the blood is normalized, which indicates their pronounced immunomodulatory effect. Endogenous immunostimulants enhance the production of interferons and increase the activity of immunocompetent cells.

• Timalin has an immunomodulatory effect, activates regeneration and reparation processes. It stimulates cellular immunity and phagocytosis, normalizes the number of lymphocytes, increases the secretion of interferons, and restores immunological reactivity. This drug is used to treat immunodeficiency conditions that have developed against the background of acute and chronic infections, destructive processes.
• "Imunofan"- a drug widely used in cases where the human immune system cannot independently resist the disease and requires pharmacological support. It stimulates the immune system, removes toxins and free radicals from the body, and has a hepatoprotective effect.

Interferons

Interferons increase the nonspecific resistance of the human body and protect it from viral, bacterial or other antigenic attacks. The most effective drugs that have a similar effect are "Cycloferon", "Viferon", "Anaferon", "Arbidol". They contain synthesized proteins that push the body to produce its own interferons.

Natural medicines include leukocyte human interferon.

Long-term use of drugs in this group minimizes their effectiveness, inhibits a person's own immunity, which ceases to function actively. Inadequate and too prolonged use of them has a negative impact on the immunity of adults and children.

In combination with other drugs, interferons are prescribed to patients with viral infections, laryngeal papillomatosis, and cancer. They are used intranasally, orally, intramuscularly and intravenously.

Preparations of microbial origin

Medicines of this group have a direct effect on the monocyte-macrophage system. Activated blood cells begin to produce cytokines that trigger innate and adaptive immune responses. The main task of these drugs is to remove pathogenic microbes from the body.

Herbal adaptogens

Herbal adaptogens include extracts of echinacea, eleutherococcus, ginseng, lemongrass. These are "soft" immunostimulants widely used in clinical practice. Preparations from this group are prescribed to patients with immunodeficiency without a preliminary immunological examination. Adaptogens start the work of enzyme systems and biosynthetic processes, activate the nonspecific resistance of the body.

The use of plant adaptagens for prophylactic purposes reduces the incidence of acute respiratory viral infections and resists the development of radiation sickness, weakens the toxic effect of cytostatics.

For the prevention of a number of diseases, as well as for a speedy recovery, patients are recommended to drink ginger tea or cinnamon tea daily, take black peppercorns.

Video: about immunity - School of Dr. Komarovsky

For adults and children, they are medicines that eliminate the imbalance of various parts of the immune system. Thus, the action of these drugs should be aimed at normalizing the parameters of immunity, i.e. to reduce high or increase low rates.

In the Russian Federation, some-effective immunomodulators-registered as immunostimulants, including those of plant origin. It is believed that the use of these drugs leads to an increase in immunity indicators, however, this is not entirely true, since immunity indicators under the influence of such drugs do not exceed the level of the physiological norm. In connection with the above, it is more correct to use the term immunomodulators .

In this section, we will dwell on the description of various types of immunomodulators, which, depending on their origin, can be divided into three large groups: exogenous, endogenous and synthetic.

General questions regarding the effectiveness of drugs are discussed in the section "How to increase immunity"?

Exogenous immunomodulators (bacterial and plant origin)

Contraindications: drug allergy, acute stage of upper respiratory tract infection, autoimmune diseases, HIV infection.

Side effects: drugs are very well tolerated, allergic reactions are rare, nausea , diarrhea.

Plant immunomodulators.

The most famous drugs of this group are: "imunal", "echinacea Vilar", "echinacea compositum CH", "echinacea liquidum".

Main indications: prevention SARS.

Contraindications: allergic to the drug, tuberculosis, leukemia, autoimmune diseases, multiple sclerosis, allergic reactions to pollen.

Side effects: drugs are very well tolerated, allergic reactions are rare ( angioedema), skin rash, bronchospasm, lowering blood pressure.

Endogenous immunomodulators

Endogenous immunomodulators can be divided into the following groups: preparations isolated from the thymus and bone marrow, cytokines (interleukins, interferons and interferon inducers) and nucleic acid preparations.
preparations isolated from the thymus and bone marrow.

Medicines derived from thymus tissue (an organ of the immune system) are: "tactivin", "timalin", "timoptin"; from the bone marrow - "myelopid".

Main indications:

• for preparations from the thymus - immunodeficiencies with a predominant lesion of the T-cell link of immunity, developing with purulent and tumor diseases, tuberculosis, psoriasis, ophthalmic herpes;
• for drugs from the bone marrow - immunodeficiencies with a predominant lesion of the humoral immunity; purulent diseases, as part of the complex therapy of leukemia and chronic infectious diseases.

Contraindications: for preparations from the thymus - an allergy to the medicine, pregnancy.
for preparations from the bone marrow - an allergy to a medicine, pregnancy with a Rh conflict.

Side effects: for preparations from the thymus - allergic reactions.
for drugs from the bone marrow - pain at the injection site, dizziness , nausea, increased body temperature.
cytokines - interleukins: natural ("superlymph") and recombinant ("betaleukin", "roncoleukin")

Main indications: for natural cytokines - treatment of wounds and trophic ulcers.
for recombinant cytokines: "roncoleukin" - purulent-inflammatory diseases, some malignant tumors; "betaleukin" - leukopenia (decreased number of blood leukocytes).

Contraindications: for natural cytokines - drug allergy, thrombocytopenia, renal and hepatic failure, epilepsy.
for recombinant cytokines: "roncoleukin" - drug allergy, pregnancy, autoimmune diseases, cardiovascular diseases; "betaleukin" - drug allergy, septic shock, high fever, pregnancy.
Side effects: for natural cytokines - exacerbation of inflammation (short-term)
for recombinant cytokines - chills, fever, allergic reactions.

cytokines - interferons: this class of immunomodulators is very extensive, it includes interferons of three varieties (alpha, beta, gamma); Depending on the origin, interferons are divided into natural and recombinant. The most common form of administration is injection, but there are other forms of release: suppositories, gels, ointments.
Main indications: very different depending on the type of interferons. Interferons are used in the treatment of viral, neoplastic diseases and even multiple sclerosis. In some diseases, the effectiveness of interferons has been proven by many studies, in others there is only moderate or even little experience of successful use.

Contraindications: drug allergy, severe autoimmune, cardiovascular diseases, epilepsy, diseases of the central nervous system, severe liver disease, pregnancy, childhood.

Side effects: Interferons have adverse drug reactions of varying severity and frequency, which may vary depending on the drug. In general, interferons (injectable forms) are not well tolerated by everyone and may be accompanied by flu-like syndrome, allergic reactions, and other undesirable drug effects.

cytokines - interferon inducers: this class of immunomodulators is represented by substances that stimulate the production of interferons in our body. There are forms of medication for oral administration, in the form of external agents, injectable forms. Trade names of interferon inducers: "cycloferon", "alloferon", "poludan", "tiloron", "neovir", "megosin", "ridostin".

Main indications: treatment of chronic viral infections as part of complex therapy.

Contraindications: allergy to medication, pregnancy, breastfeeding, children's age (up to 4 years).

Side effects: allergic reactions.
nucleic acid preparations: "ridostin" and "derinat".
Main indications: secondary immunodeficiencies, manifested by viral and bacterial infections.

Contraindications: drug allergy, pregnancy, breastfeeding, children's age (up to 7 years), myocardial disease, severe renal and hepatic insufficiency.
Side effects: allergic reactions, fever.

Immunomodulators of synthetic origin

This group of immunomodulators is represented by drugs that are different in their chemical structure, and therefore each drug has its own characteristics of the mechanism of action, tolerability and undesirable effects. This group includes: isoprinazine, galavit, gepon, glutoxim, polyoxidonium, imunofan, thymogen, licopid.

Main indications: secondary immunodeficiencies associated with chronic viral and bacterial infections.

Contraindications: drug allergy, pregnancy, breastfeeding. "Isoprinazine" is also contraindicated in case of padagra, urolithiasis, chronic renal failure and arrhythmias.

Side effects: allergic reactions, soreness at the injection site (for injectables), exacerbation of gout(isoprinasine), etc.

Immunoglobulins

Intravenous immunoglobulins are drugs that are protective blood proteins that protect us from bacteria, viruses, fungi and other foreign microorganisms.

There are immunoglobulins (antibodies) directed against a certain foreign particle (antigen), in which case these antibodies are usually called monoclonal (i.e. all as one clone are the same), if the immunoglobulins (antibodies) are directed against many foreign particles they are called polyclonal, such polyclonal antibodies are intravenous immunoglobulins. Monoclonal antibodies are drugs of the 21st century that can effectively fight some tumors and autoimmune diseases. However, polyclonal antibodies are very useful as well. they are successfully used in a variety of diseases. Intravenous immunoglobulins usually consist predominantly of immunoglobulins G, however, intravenous immunoglobulins are also enriched with immunoglobulins M ("pentaglobin").

The main intravenous immunoglobulins registered in the Russian Federation include: intraglobin, octagam, humaglobin, cytotect, pentaglobin, gamimn-N, etc.

Main indications: primary immunodeficiencies associated with a lack of immunoglobulin synthesis, severe bacterial infections, autoimmune diseases (Kawasaki disease, Guillain-Barré syndrome, some systemic vasculitis, etc.), idiopathic thrombocytopenic purpura, etc.

Contraindications: allergic reactions to intravenous immunoglobulins.
Side effects: allergic reactions, increase or decrease in blood pressure, fever, nausea and others. With slow infusion, many patients tolerate these drugs well.