Propaming and anti-inflammatory cytokines Table. Cytokines - classification, role in the body, treatment (cytokinotherapy), reviews, price. What is cytokines

04.01.2021 Popular treatment

Have you ever heard of cytokines? The term "cytokine" comes from a combination of two Greek words: "cyto" means a cell and "Kinos" means movement. Anti-inflammatory cytokines play an important role in both health and diseases, especially when it comes to inflammatory conditions, autoimmune diseases, chronic and acute infections, injuries, problems with conception and pregnancy, and even cancer ().

According to one scientific article, which emphasizes the role of cytokines in women's health, including premature genera and endometriosis, "progress in understanding biology of cytokines led to an understanding of the importance of cytokines in all areas of medicine" ().

So what is cytokines? They represent the category of small proteins that provide communication between cells. There are several families of cytokines that are produced differently, behave differently and have different activity in the body.

On the other hand, anti-inflammatory cytokines can help us deal with infections and have a positive impact on our immune system and inflammation. However, when some cytokines do not behave perfectly or overproduce, it may cause a disease.

It may be difficult to explain cytokines without excessive scientific language, but better understanding these powerful molecules, we can improve or even prevent some very common, but serious health problems, including arthritis, cancer and much more.

What is cytokines

Simple determination of cytokines: a group of proteins created by the immune system, which act as chemical messengers. Cytokines are proteins, peptides or glycoproteins secreted by lymphocytes and monocytes that regulate immune responses, hemopoies and lymphocyte development ().

These minor proteins act as intermediaries between cells, and are engaged in transferring vital information that affects many things in the body, ranging from embryonic development to modulating bone structure and maintaining homeostasis (). Cytokines are probably the most famous for their key role as mediators and inflammatory reaction regulators. They are actually able to stimulate the motion of the cells to the areas of infection, injuries and inflammation.

Cytokines are secreted by other types of cells in high concentrations and can affect either the cell of origin (autocrine action), for the cells nearest to them (paracryn action) or remote cells (endocrine or system action) (). As a rule, cytokines can act synergistically (working together) or antagonistically (acting in opposition). There are several different groups or cytokines families, which are structurally similar, but have a varied spectrum of functions.

Classification of cytokines

Several subcategories of cytokines, which include both pro-inflammatory and anti-inflammatory cytokines are distinguished.

Articles on the topic:

Propameable cytokines are mainly produced by activated macrophages and are involved in the activation of inflammatory reactions.

Scientific data link these pro-inflammatory proteins with various diseases, as well as with the process of pathological pain. Meanwhile, anti-inflammatory cytokines are molecules that help to regulate the immune system and control the pro-inflammatory response of cytokines ().

According to the classification of cytokines, there are the following main family of cytokines and their key characteristics or actions: (,)

Chemokina: Direct cell migration, adhesion and activation
Interferons: Antiviral proteins
Interleukins: A variety of actions depending on the type of interleukin cells
Monokines: Powerful molecules, produced monocytes and macrophages that help to direct and regulate immune responses
Lymphokins. Protein mediators are usually produced by lymphocytes (leukocytes) to direct the reaction of the immune system by transmitting signals between its cells.
Tumor necrosis factor: regulates inflammatory and immune responses

There are also erythropoietin, also called hematopoietin, which is a cytokine hormone, which regulates the production of erythrocytes (erythrocytes).

Properties cytokines

1. Regulation of the immune system

Cytokines play a very important role in our immune response. The two main producers of cytokines are T-helper cells and macrophages. What it is? T-helper cells help other cells in an immune response, recognizing alien antigens and secreting cytokines, which are then activated T and B cells. Macrophages surround and kill microorganisms, absorb foreign material, remove dead cells and enhance immune responses.

Impacting the cells of the immune system and interacting with them, cytokines are able to regulate the body's response into illness and infection. Cytokines affect both our congenital and adaptive immune responses (). The optimal production and behavior of our cytokines is the key to the health of our immune system.

In one scientific article published in 2014, the influence of cytokines, such as interferons (INF) and interleukins (IL), on mycobacterial infections, in particular tuberculosis. Researchers come to the conclusion: "In general, the IFN cytokine family seems to be critical for the outcome of mycobacterial infection," and plays an important role in curbing the growth of bacteria ().

3. Reducing pain in arthritis

Since cytokines regulate various inflammatory reactions, it is not surprising that studies show which important role is these proteins in arthritis, inflammatory diseases of the joints. As mentioned earlier, overproduction or improper production of certain cytokines by the body may result in a disease.

According to the scientific article published in 2014, entitled "The role of inflammatory and anti-inflammatory cytokines in Osteoarthritis pathogens", interleukin-1-beta and the necrosis factor of tumor-alpha, are believed to be the main inflammatory cytokines involved in osteoarthritis (OA). While interleukin-15 is associated with the pathogenesis of rheumatoid arthritis (RA) ().

Although it is obvious that pro-inflammatory cytokines are at elevated levels in patients with arthritis, their anti-inflammatory options were also found in the synovial shell and in the synovial fluid of patients with RA. To date, scientific research on animal models demonstrated the ability of anti-inflammatory cytokines to reduce pain arising from arthritis. However, they do not prevent damage to the joints. Clinical trials in humans continue, and we hope that in a short time some useful results for patients with arthritis () will appear.

4. Reducing inflammation

Anti-inflammatory cytokines are known for their ability to reduce inflammation in the body. And we know that inflammation is the cause of most diseases (). According to the scientific article called "Cytokines, inflammation and pain", which was published in the journal International Anesthesiology Clinics., from all anti-inflammatory cytokines interleukin 10 (IL-10) has one of the strongest inflammatory properties and is able to suppress the expression of pro-inflammatory cytokines, such as interleukin 6 (IL-6), interleukin 1 (IL-1) and the alpha tumor necrosis factor (TNF -α).

IL-10 is also capable of suppressing cytokine receptors, so it is capable of reduced products, as well as the function of molecules of pro-inflammatory cytokines on several levels. According to this article, the introduction of the IL-10 protein demonstrated pain relief in various states, such as peripheral neuritis, excitotoxic damage to the spinal cord and damage to the peripheral nerve.

In addition, recent clinical studies show that low blood levels IL-10 and interleukin 4 (also anti-inflammatory cytokine) can be important factors when it comes to chronic pain. Because it was found that patients struggling with chronic widespread pain have low concentrations of these two cytokines ().

4. Antitumor activity

Certain cytokines are currently used in cancer immunotherapy, including treatment of leukemia, lymphoma, melanoma, bladder cancer and kidney cancer. Our body naturally produces cytokines. But when they are used for the natural treatment of cancer, these proteins are created in the laboratory, and then introduced in large doses than the body usually does independently.

According to the National Cancer Institute, Interleukin-2 was the first cytokine that had a therapeutic effect during cancer. In 1976, Robert Gallo, Dr. Medicine and Francis Rusketti, Dr. Philosophy, demonstrated that this cytokine can "significantly stimulate the growth of T-cells and natural killers, which are an integral part of the human immune response."

After almost 10 years, another group of researchers led by Stephen Rosenberg, a doctor of medical sciences, as reported, successfully cured several patients with common metastatic renal cellular cancer (type of renal cancer) and melanoma, giving them interleukin-2. Interleukin-2 became the first anti-cancer immunotherapy approved by the FDA in the United States. To date, it is still used to treat metastatic melanoma and kidney cancer ().

Side effects of interleukin-2 may include chills, fever, fatigue, weight gain, nausea, vomiting, diarrhea and low blood pressure. Rarely, but there is also a violation of heart rhythm, chest pain and other heart problems. Other interleukins continue to be studied as possible cancer treatment ().

How to ensure a healthy balance of cytokines

Cytokines are an important topic of scientific research that continue to this day. But it is still believed that a healthy diet rich in useful nutrients, exercise and reduced stress, can help maintain a healthy balance of cytokines in the body.

It is assumed that the state of cytokines depends on the state of the power supply. Chronic nutritional deficiency adversely affects our immune response, which includes a decrease in the production and activity of cytokines (). Thus, the use of whole and anti-inflammatory foods is a key way to increase the status of cytokines in our organism.

In vitro studies also showed that cinnamon extract increases the level of interleukin-10, at the same time suppressing pro-inflammatory cytokines on experimental models of induced inflammatory bowel disease ().

One of the plant products that reduce pro-inflammatory cytokines is hemp oil. Read more about our site.

There are also products that need to be avoided. First of all, it is:

refined sugar
milk products.

As the United States Foundation indicates, studies have shown that the processed sugars cause the emission of inflammatory cytokines ().

In a study published in Journal of Physiology., The effect of long-term physical exertion on pro-inflammatory and anti-inflammatory cytokines was studied. The researchers found that while exercise increased some pro-inflammatory cytokines, the levels of anti-inflammatory interleukin-10 in the plasma showed a 27-fold increase immediately after exercise, and cytokine inhibitors were also released. Thus, in general, the study suggests that physical exercises can increase anti-inflammatory cytokines that help reduce the inflammatory response, which may arise as a result of long-intensive activities ().

Studies have shown that at first stress can cause suppression of inflammatory cytokines and activation of anti-inflammatory cytokines. However, long-term chronic stress further increases pro-inflammatory cytokines, which then lead to inflammatory reactions and ultimately can cause various diseases (). So this is another reason for practicing meditation daily, hot or contrast shower as natural ways to remove stress.

Key points about cytokines

Cytokines are a group of proteins created by the immune system that act as chemical messengers.
There are several families of these signal proteins, including inflammatory or anti-inflammatory cytokines.
They are especially important for immune function and inflammatory reactions.
Cytokine studies continue, but so far current or potential advantages include: enhancing the immune system, arthritis anesthesia, reduction of inflammation and growth of tumors.

Methods for stimulating a healthy function and a balance of cytokines include a healthy diet based on whole products that contain anti-inflammatory components and eliminates inflammatory products such as sugar and milk. Reducing stress, including regular exercise, can also contribute to the optimal status of cytokines.

The activation of the cells of the inflammation zone is manifested in the fact that the cells begin to synthesize and highlight a plurality of cytokines that have an impact on nearby cells and cells of remote organs. Among all these cytokines there are those that contribute to (pro-inflammatory), and those that prevent the development of the inflammatory process (anti-inflammatory). Cytokines cause effects similar to manifestations of sharp and chronic infectious diseases.

Perfect cytokines

Speaking of pro-inflammatory cytokines are capable of 90% of lymphocytes (a variety of leukocytes), 60% of tissue macrophages (cells that can capture and digest bacteria). Stimulants of production of cytokines are causative agents of infections and cytokines themselves (or other inflammation factors).

Local separation of pro-inflammatory cytokines causes the formation of the focus of inflammation. With the help of specific receptors, pro-inflammatory cytokines are associated and involved in the process of other cell types: skin, connective tissue, inner walls of vessels, epithelial cells. All these cells also begin to produce pro-inflammatory cytokines.

The most important pro-inflammatory cytokines are IL-1 (interleukin-1) and TNF alpha (factor of necrosis of the alpha tumor). They cause formation on the inner shell of the walls of the vessels of the adhesion (sticking) of the vessels: first leukocytes stick to the endothelium, and then penetrate through the vascular wall.

These pro-inflammatory cytokines stimulate the synthesis and separation of leukocytes and endothelial cells of other pro-inflammatory cytokines (IL-8 and others) and thereby activate the cells on the products of inflammatory mediators (leukotrienes, histamine, prostaglandins, nitrogen oxide and others).

When infection in the body penetrate the production and release of IL-1, IL-8, IL-6, TNF alfa begins at the site of the introduction of the microorganism (in the cells of the mucous membrane, leather, regional lymph nodes) - that is, cytokines activate local protective reactions.

Both TNF alpha and IL-1, except for local action, have a systematic: activate the immune system, endocrine, nervous and hematopois system. Propaming cytokines are capable of calling about 50 different biological effects. Their targets may be almost all the fabrics and organs.

For example, anemia for acute and chronic infectious diseases is the result of the impact on the organism of pro-inflammatory cytokines (interleukin-1, interferon-beta, interferon-gamma, FNF, neopterina). They suppress the growing of the erythroid sprout, the release of iron from the cells of the macrophages and depress the production of erythropoietin in the kidneys. Cytokines act very effectively and quickly.

Anti-inflammatory cytokines

Control over the action of pro-inflammatory cytokines is carried out by anti-inflammatory cytokines, which include IL-4, IL-13, IL-10, TFR-beta. They not only can suppress the synthesis of pro-inflammatory cytokines, but also to promote the synthesis of receptor antagonists of interleukins (Rail or Rail).

The ratio between anti-inflammatory and pro-inflammatory cytokines - important moment In regulating the emergence and development of the inflammatory process. This balance depends on the course of the disease, and its outcome. It is cytokines that stimulate the production of blood coagulation factors in the cells of the endothelium of blood vessels, the products of chondrolytic enzymes, contribute to the formation of scar tissue.

Cytokines and immune response

All cells in the immune system have certain clear functions. The consistent interaction of them is carried out by cytokines - regulators of immune reactions. They ensure the exchange of information between the cells of the immune system and coordinate their actions.

The set and number of cytokines is the matrix of signals (frequently changing), which affect the cell receptors. The complex nature of these signals is explained by the fact that each cytokine can suppress or activate several processes (including the synthesis of its or other cytokines), the formation of receptors on the cell surface.

Cytokines provide interconnection within the immune system between the specific immunity and non-specific protective reaction of the body, between the humoral and cellular immunity. It is cytokines that communicate between phagocytes (providing cellular immunity) and lymphocytes (cells of humoral immunity), as well as between different lymphocytes in their function.

Through cytokines, T-helpers (lymphocytes, "recognizing" alien proteins of microorganisms) transmit the T-killeram team (cells destroying alien protein). Similarly, with the help of cytokines, T-suppressors (type of lymphocytes) control the function of T-killers and transmit them information about the cessation of cell destruction.

If such a connection is broken, then the death of cells (already own for the body, and not alien) will continue. That is how autoimmune diseases are developing: Synthesis IL-12 is not controlled, the cell-mediated immune response will be excessively active.

The course and outcome of the infectious disease depends on the ability of its causative agent (or its components) to cause synthesis of cytokine IL-12. For example, the type of Candida Albicans mushrooms can cause Synthesis IL-12, which contributes to the development of effective cellular protection against this pathogen. Leinsmania suppresses the synthesis IL-12 - a chronic infection develops. HIV suppresses the synthesis of IL-12, and this leads to defects of cellular immunity with AIDS.

Cytokines regulate the specific immune response of the body to implement the pathogen. If local protective reactions turned out to be insolvent, cytokines act at the system level, that is, they affect all systems and organs that are involved in maintaining homeostasis.

When they are exposed to the CNS, the entire complex of behavioral reactions is changing, the synthesis of most hormones, protein synthesis and plasma composition occurs. But all the changes occurring are not random: they are either necessary to increase protective reactions, or contribute to switching the body's energy to the fight against pathogenic effects.

It is the cytokine that communicates between the endocrine, nervous, hematopoietic and immune systems involve all these systems in the formation of a complex protective reaction of the body to introduce a pathogenic agent.

Macrofag absorbs bacteria and highlights cytokines (three-dimensional model) - video

Analysis on polymorphism of cytokine genes

Analysis on polymorphism of cytokine genes is a genetic study at the molecular level. Such studies represent a wide amount of information to identify the presence of the examined person of polymorphic genes (pro-inflammatory options), to predispose the predisposition to various diseases, develop a program for the prevention of diseases for this particular person, etc.

In contrast to single (sporadic) mutations, polymorphic genes are found approximately 10% of the population. The carriers of such polymorphic genes have an increased activity of the immune system in operational interventions, infectious diseases, mechanical influences on the tissue. In the immunogram of such persons, a high concentration of cytotoxic cells (killer cells) is often revealed. In such patients, septic, purulent complications occur more often.

But in some situations such an increased activity of the immune system may interfere with: for example, with an extracorporeal fertilization and a proprietary sweep. And the combination of interleukin-1 or Il-1 (IL-1) pro-inflammatory genes (IL-1), the interleukin-1 receptor antagonist (Rail-1), the tumoronecrit-alpha (TNF-Alpha) is a predisposing factor for non-obscure during pregnancy. If during the examination, the presence of pro-inflammatory genes of cytokines is detected, then special preparation for pregnancy or eco (extracorporeural fertilization) is required.

Analysis on a cytokine profile includes the detection of 4 polymorphic options for genes:

interleukin 1-beta (IL-beta);
receptor antagonist interleukin -1 (ILRA-1);
interleukin-4 (IL-4);
tomorekrotic Factor Alpha (TNF Alpha).

For the analysis of the analysis does not require special training. The material for the study serves as a scraping with a mucous cheek.

Modern studies have shown that with the usual unbearab of pregnancy in the body of women, genetic factors of thrombophilia are often detected (tendency to thrombosis). These genes can lead not only to unbearable, but also to placental insufficiency, delay in the growth of the fetus, late toxicosis.

In some cases, the polymorphism of thrombophilia genes in the fetus is more pronounced than the mother, since the fruit also receives the genes from the Father. The mutations of the Prolrombina gene lead to almost the one hundred percent intrauterine fetal death. Therefore, there are particularly difficult cases of inconsection requires surveys and husband.

Immunological examination of the husband will help not only determine the pregnancy forecast, but also reveals the risk factors for its health and the possibility of using prevention measures. In the case of identifying risk factors, the mother is advisable then to conduct a child's survey - this will help develop an individual disease prevention program in a child.

With infertility, it is advisable to identify all currently known factors that can lead to it. A complete genetic study of polymorphism genes includes 11 indicators. The survey can help identify the predisposition to disorders of the function of the placenta, an increase in blood pressure, preeclampsia. Accurate diagnosis of infertility causes will make it necessary to carry out the necessary treatment and will give the opportunity to preserve pregnancy.

An extended hemostasiogram can give information not only for obstetric practice. With the help of the study of polymorphism of genes, genetic factors of predisposition to the development of atherosclerosis, ischemic heart disease, predict its course and the likelihood of the development of myocardial infarction. Even the likelihood of sudden death can be calculated using a genetic study.

The influence of polymorphism of genes on the pace of development of fibrosis in patients with chronic hepatitis C is also studied, which can be used in predicting the flow and outcome of chronic hepatitis.

Molecular genetic studies of multifactorial diseases help not only in creating an individual forecast for the state of health and prevention measures, but also in the development of new therapeutic methods with the use of anticytokine and cytokine drugs.

Cytokinotherapy

Treating tumor diseases

Cytokinotherapy can be used at any (even IV) stage of malignant disease, in the presence of severe concomitant pathology (liver and renal or cardiovascular failure). Cytokines selectively destroy only the cells of the malignant tumor and do not affect healthy. Cinotherapy can be used as an independent method of treatment or to enter into complex therapy.

Immunological studies in oncological patients showed that most malignant diseases are accompanied by impaired immunological response. The degree of suppression depends on the size of the tumor and the treatment conducted (radiation therapy and chemotherapy). Data was obtained on the biological effects of cytokines (interleukin-2, interferon, the tumorial factor and others).

Cinotherapy is used in oncology for several decades. But used to be used mainly interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) - efficient only with skin melanoma and kidney cancer. In recent years, new drugs have been created, readings have expanded to effectively use them.

One of the drugs of cytokines is a tumor necrosis factor (TNF alpha) - acts through receptors located on a malignant cell. This cytokine is produced in the human body by monocytes and macrophages. When interacting with the cylinder malignant cell receptors launches the death program of this cell.

FNO-ALPA began to be used in oncological practice in the United States and in Europe in the 1980s. It is used and now. But the high toxicity of the drug limits its application only by those cases when it is possible to isolate the organ with the tumor process from the total blood flow (kidney, limb). The drug in this case circulates with the help of an artificial blood circulation apparatus only in the affected organ, and does not fall into the overall blood flow.

In Russia, in 1990, the preparation of refdium (FNF-T) was created due to the merger of thymsimin-alpha genes and tumor necrosis factor. It is 100 times less toxic than FLN, clinical trials have passed and since 2009 is allowed to use in the treatment of various species and localization of malignant tumors.

Given the decrease in the toxicity of the drug, it can be introduced intramuscularly or subcutaneously. The drug has an action to the primary focus of the tumor, and at metastases (including distant), unlike the drug FN-Alfa, which could only have an action on the primary hearth.

Another promising drug from the number of cytokines is interferon-gamma (IFN Gamma). On its basis in 1990, in Russia was created in Russia. It has a direct effect on the tumor cells or launches the apoptosis program (the cell itself programms and performs its death), increases the effectiveness of immune cells.

The drug also passed clinical trials and since 2005 is allowed to use in the treatment of malignant tumors. The drug activates those receptors on a malignant cell, which then interacts the refrigera. Therefore, most often cytokinotherapy with refrigerability with the use of ingarone.

The method of administering these drugs (intramuscular or subcutaneous) allows treatment in outpatient conditions. Cinotherapy is contraindicated only during pregnancy and autoimmune diseases. In addition to direct impact on the malignant cell, ingaron and refriges have an indirect action - activate own cells Immune system (T-lymphocytes and phagocytes) increase general immunity.

Unfortunately, the effectiveness of cytokinotherapy is only 30-60%, depending on the stage and localization of the tumor, the type of malignant neoplasm, the prevalence of the process, the overall state of the patient. The higher the stage of the disease, the less pronounced the effect of treatment.

But even in the presence of multiple and remote metastases and the impossibility of conducting chemotherapy (due to the severity of the overall condition of the patient), positive results are noted in the form of improving overall health and suspension of the further development of the disease.

The main directions of the actions of modern drugs-cytokines:

direct impact on the cells of the tumor itself and metastases;
amplification of the antitumor effect of chemotherapy;
prevention of metastases and tumor relapses;
reducing adverse reactions of chemotherapy by oppression of blood formation and immunosuppression;
treatment and prevention of infectious complications in the treatment process.

Possible options for the use of cytokinotherapy:

the complete disappearance of the tumor or reduce its size (due to the launch of apoptosis - the programmed death of the tumor cells);
process stabilization or partial tumor regression (when the cell cycle arrest is launched in tumor cells);
lack of effect - continues growth and metastasation of the tumor (with the insensitivity of tumor cells to the drug due to mutations).

From the above, it can be seen that the clinical result of the use of cytokinotherapy depends on the characteristics of tumor cells in the patient himself. To assess the effectiveness of the use of cytokines, 1-2 courses of treatment are carried out and evaluated the process dynamics through various instrumental examination methods.

The possibility of using cytokinotherapy does not mean the refusal of other methods of treatment (operational intervention, chemotherapy or radiation therapy). Each of them has its advantages of exposure to the tumor. All shown and accessible methods of treatment in each specific case should be used.

Cytokines greatly facilitate the portability of radiation and chemotherapy, prevent the occurrence of neutropenia (reduction of the number of leukocytes) and the development of infections in the process of chemical therapy. In addition, Refnot increases the efficiency of most chemotherapy. The use of it in combination with ingaron a week before the start of chemotherapy and the continuation of the use of cytokine after the course of chemotherapy will protect against infections or cure them without antibiotics.

The cytokinotherapy scheme is prescribed to each patient individually. Both drugs practically do not show toxicity (in contrast to chemotherapy), they do not have adverse reactions and are well tolerated by patients, do not render an oppressive effect on blood formation, increase antitumor specific immunity.

Treatment of schizophrenia

Studies found that cytokines are involved in psycho-imaging reactions and ensure the conjugate work of nervous and immune systems. The balance of cytokines regulates the process of regeneration of defective or damaged neurons. This is based on the use of new methods of treating schizophrenia - cytokinotherapy: the use of immunotropic cytokine-containing drugs.

One method is the use of anti-TNF alpha and anti-IFN gamma antibodies (antibodies against the necrosis-alpha necrosis and interferon-gamma). The drug is injected intramuscularly within 5 days by 2 p. in a day.

There is also a method of use of a composite solution of cytokines. It is introduced in the form of inhalation using a nebulizer of 10 ml per 1 introduction. Depending on the patient's condition, the drug is administered every 8 hours. In the first 3-5 days, then for 5-10 days - 1-2 rubles per day and the subsequent decrease in the dose to 1 p. In 3 days for a long time (up to 3 months), with complete abolition of psychotropic drugs.

Intranasal use of a solution of cytokines (containing IL-2, IL-3, GM-KSF, IL-1BET, IFN-gamma, FNF-alpha, erythropoietin) helps to increase the effectiveness of patients treatment with schizophrenia (including the first attack of the disease), more Long and resistant remission. These methods are used in the clinics of Israel and in Russia.

History of cytokines

The activity of cytokines was discovered at the end of 1960. Initially assumed that they serve as amplification factors acting antigen-dependent, increasing the proliferative responses of T-cells i.gery (L.Gery) and co-authors showed that the macrophages released the mitogenic factor of Timocytes called them lymphocytivating factor (LAF). This look has changed radically when they found that the supernatant of mononuclear blood mononuclear bloods stimulated by mitogen causes long-term proliferation of T-cells in the absence of antigens and mitogen.

Soon after, it turned out that for isolation and clonal expansion of functional T cell lines, a factor produced by T cells can be used. This factor obtained from T-cells, various researchers gave different names; The most famous among them - T-cell growth factor (TCGF). Cytokines produced by lymphocytes were called lymphocins, and produced by monocytes and macrophages - monocins.

The results of the study of the cellular source of lymphokinov and monokines, ultimately, revealed that these factors were not the products of exclusively lymphocytes or monocytes / macrophages, which complicated the understanding of the issue. Thus, as the general name of these glycoprotein mediators, the term "cytokine" was adopted.

Due to the need to generate an agreement regulating the definition of factors obtained from macrophages and T-cells, in 1979, an international working group was established, which was developing their nomenclature. Since cytokines transferred a signal from leukocyte to leukocyte, the term "interleukin" (IL) was proposed. The macrophaghal factor LAF and the T-cell growth factor was given by the names of the In-Terleikin-1 (IL-1) and interleukin-2 (IL-2), respectively. To date, 29 interleukins were investigated, and their number will undoubtedly increase, since attempts continue to identify new representatives of this family of cytokines.

As new knowledge about the functional properties of cytokines in terms, originally intended to determine their functions, began to invest a wider meaning. This is evidenced by the fact that the terminology adopted in 1979 is obsolete. It is well known that many interleukins have important biological effects on cells that do not belong to the immune system. For example, IL-2 not only activates T-cell proliferation, but also stimulates osteoblasts - cells forming bone.

The transforming growth factor β (TGFβ) also acts on cells of different types, including fibroblasts of connective tissue, T- and in lymphocytes. Thus, cytokines mainly have playiotropic properties, since they can affect the activity of a plurality of different cell types. In addition, among cytokines, the redundancy of functions is expressed, which is proved, for example, the ability to activate growth, survival and differentiation of V- and T-cells with more than one cytokine (for example, IL-2, and IL-4 can function as T-cell factors growth). This excess is partially explained by the use of common signaling subunits of cytokine receptor with certain groups of cytokines.

Ultimately, cytokines rarely, if at all ever, act in the body alone. Thus, target cells are susceptible to a surrounding containing cytokines that often show additive, synergistic or antagonistic properties. In the case of synergies, the joint action of two cytokines causes a more pronounced effect than the sum of the effects of individual cytokines. Conversely, when one cytokine inhibits the biological activity of the other, they speak of their antagonism.

Since 1970, knowledge of cytokines is rapidly increased due to their identification, determination of functional characteristics and molecular cloning. A convenient nomenclature developed earlier on the basis of cellular sources or functional activity of certain cytokines was not widely supported. Nevertheless, from time to time, as the general functional features of several glycoproteins are found, additional terms are introduced, which determine this family of cytokines.

In particular, the term "Chemokina", adopted in 1992, determines the family of nearby chemotactic cytokines having conservative sequences and are powerful attractants for different leukocyte populations, such as lymphocytes, neutrophiles and monocytes. For immunologists' students, studying a rapidly expanding list of cytokines with a variety of functional characteristics can represent significant difficulties. However, it is enough to focus on individual cytokines worthy of particular attention, which will be an interesting and accurate task.

General properties of cytokines

General functional properties

Cytokines have some common functional features. Some, such as interferon-y (ifny) and IL-2, are synthesized by cells and quickly secreted. Others, such as tumor necrosis factor A (TNFα) and TNFβ, can be secreted or expressed as proteins associated with membranes. Most cytokines have a very short half-life; Consequently, cytokine synthesis and their functioning usually occur impulsively.

Fig. 11.1. Autocrine, Parakrine and endocrine properties of cytokines. For example, the brain is responsible for the impact of cytokines as an endocrine effect

Like the polypeptide cytokine hormones ensure the relationship between cells in very low concentrations (usually from 10-10 to 10-15 m). Cytokines can act locally and on the cell that secreted them (autocrino), and on other close cells (Paraconno); Moreover, they can act systemically as hormones (endocrino) (Fig. 11.1). Just like other polypeptide hormones, cytokines show their functions, binding to specific receptors on target cells. In this case, the cells regulated by certain cytokines should express the receptor for this factor.

Thus, the activity of corresponding cells can be adjusted by the amount and type of cytokines to which they are sensitive, or by increasing / decreasing the expression of cytokine receptors, which themselves can be regulated by other cytokines. A good example of the last position is the ability of IL-1 to increase the expression of receptors for IL-2 on T cells. As noted earlier, it illustrates one general trait of cytokines, namely, their ability to act jointly, creating the effect of synergies, which increases their effects on a single cell.

At the same time, some cytokines are in antagonistic relations with one or more cytokine and thus inhibit each other's effect on this cell. For example, cytokines secreted by T-helpers (TN1) are an IFNY, which activates macrophages, inhibits B cells and is directly toxic for certain cells. The TN2 cells secrete il-4 and IL-5, which are activated by B cells and IL-10, which in turn inhibits the activation of macrophages (Fig. 11.2).

Fig. 11.2. Cytokines produced by TN1-WATN2-cells

When cells produce cytokines or chemokins in response to various incentives (i.e., infectious agents), they create a concentration gradient, which allows you to control or direct cell migration, also called chemotaxis (Fig. 11.3). Cellular migration (i.e. chemotaxis neutrophils) is necessary for the development of inflammatory reactions arising from the local penetration of microorganisms or another injury.

Fig. 11.3. Neutrophil chemotaxis stages (reversible binding, subsequent activation, adhesion) and transdenry migration (Promotion between endothelial cells forming the wall of the blood vessel, extravasation)

Chemokins play a key role in providing signals that increase the expression of adhesive molecules expressed on endothelial cells to ensure chemotaxis of neutrophils and transcendothelial migration.

General systemic activity

Cytokines can act directly at the point of secretion and remotely, up to system effects. Thus, they play a decisive role in strengthening the immune response, since the release of cytokines from just a few cells activated by the antigen leads to activation of a plurality of cells of various types, which are not necessarily antigensical or are located directly in this area. This is especially pronounced in GZT reactions, in which the activation of rare antigenspecifical T cells is accompanied by the release of cytokines. As a consequence of cytokines in this zone, monocytes are attracted in large quantities, significantly exceeding the initially activated T-cell population.

It should also be noted that the products of high concentrations of cytokines under the influence of powerful incentives can run destructive system effects, such as toxic shock syndrome, discussed further in this chapter. The use of recombinant cytokines or antagonists of cytokines capable of influencing different physiological systems, ensures the possibility of therapeutic correction of the immune system based on the spectrum of biological activity, which is associated with these cytokine.

Common cell sources and cascade of events

A certain cell can produce many different cytokines. Moreover, one cell may be a target for many cytokines, each of which binds to its specific receptors on the cell surface. Consequently, one cytokine can affect the action of another, which can lead to additive, synergistic or antagonistic effect on the target cell.

The interactions of the set of cytokines secreted during a typical immune response are usually called a cytokine cascade. Basically, it is this cascade that determines whether the response to the antigen will be mainly anti-indirect (and if so which antibody classes will be synthesized) or cellularly mediated (and if so, which cells will be activated - possessing a cytotoxic effect or participating in the GZT). Control mechanisms, also mediated by cytokines, which help to determine the set of cytokines released after the activation of CD4 + -T-cells.

It seems that in the initiation of the cytokine response of these cells, an antigen stimulation plays a leading role. Thus, depending on the nature of the antigenic signal and the set of cytokines associated with the activation of T cells, the naive effector CD4 + -t cell will acquire a certain cytokine profile, which will unambiguously determine the type of generated immune response (mediated by antibodies or cells). The cytokine cascade associated with the types of an immune response also determines which other systems are activated or depressing, as well as the severity and duration of the immune response.

Common receptor molecules

Cytokines typically have overlapping, redundant functions: For example, IL-1, and IL-6 cause fever and several other common biological phenomena. At the same time, these cytokines have both unique properties. As it will be discussed, some cytokines for the spread of their action on target cells use receptors consisting of several polypeptide chains, with some of these receptors have at least one common receptor molecule, which is called the total y-chain (Fig. 11.4). The total y-chain is an intracellular signal molecule. This data helps to explain the presence of overlapping functions from different cytokines.

Fig. 11.4. The structural characteristics of the members of the family of cytokine receptors I class. The same ү-chain (green) transfers the signal inside the cell

R.KAKO, D.SANSHAIN, E. BENDZHINI

Cytokines - protein natural substances with low molecular weight, which are produced by almost all immune cells. They serve as peculiar chemical mediators within the immune system. But they cannot be called only by immune factors, since they take part in the blood formation processes, the intersystem transmission of signals and have the ability to interact with cells of other organs and systems, which makes it possible to maintain the constancy of the internal environment. These substances ensure control of inflammation and hypersensitivity reactions, under certain conditions contribute to damage to their own tissues of the body.

Cytokines are important components of the inflammatory process necessary to implement the protective functions of the immune system. In the development of these reactions, pro-inflammatory cytokines, growth factors, chemokine are involved. However, in some cases it is necessary to suppress and restrain the inflammatory process. For this, there are anti-inflammatory cytokines.

General properties

Cytokine binds to the receptor on the cell membrane, which stimulates the cell to perform its function.

All cytokines have not only their individual features, but also have common functional features:

To perform their function, they are associated with a specific receptor on the cell membrane.
Some of them interact with different target cells, others - only with certain cell lines.
The synthesis of these substances occurs impulsively. They have a rather short half-life and a short action.
Cytokines are effective in very low concentrations.
They can cause local reactions or have a systematic effect.
Cytokines interact with each other. So, one of them can influence the activities of another, stimulating, reinforcing or relaxing it.
For them, overlapping redundant functions are characterized (one and the same effect causes several cytokines).
The same cell is capable of producing various cytokines.
One type of cytokines can be produced by various cells.

Perfect cytokines

Cytokines with pro-inflammatory activity begin to secrete in the body as a result of damage or penetration of the infectious agent. They produce activated lymphocytes, monocytic cells, dendritic cells, etc. important representatives This group of cytokines are:

interleukin-1;
interleukin-6;
tumor necrosis factor α;
interleukin-17 and 18.

Cytokines responsible for the inflammatory response are synthesized and secreted into pathological focus quite quickly. They appear there for an hour and begin to provide their action, forming inflammation zone:

induced expression of membrane receptors sensitive to inflammation factors;
enhance the movement of leukocytes from the bloodstream into the pathological center;
stimulate the synthesis of other cytokines with a similar effect;
cause fever;
increase the products of protein substances of the acute phase of inflammation;
activate the activity of the nervous system and the internal secretion glands.

It should be noted that in high concentrations these substances are capable of causing pathological reactions. The most striking example is the septic shock.

Interleukin-1 combines about 11 classes of protein molecules. 5 of them are akivny cytokines, the remaining functions are not known. The targets for interleukin-1 may be any cell cells, but most sensitive to it are most sensitive:

endothelium vessels;
leukocytes;
chondrocytes;
epithelial cells;
nervous fabric.

Under its influence in the body, more than 50 types of biological reactions are being implemented. It activates all pro-inflammatory genes, causes the migration of leukocyte cells into the focus of inflammation, increasing their phagocytic activity and a bactericidal action. It also affects the vascular tone and blood circulation in this area. In addition, interleukin-1 has multiple system effects:

affects the hypothalamus and causes a temperature reaction;
takes part in the development of general manifestations of the inflammatory process (general weakness, adamiya, poor appetite, drowsiness);
enhances;
stimulates the yield of granulocytes from the blood-made zone of bone marrow;
when damaged cartilage and bone tissue can cause their destruction and others.

Interleukin-6 is a cytokine of a wide action. It takes part in the induction of almost the entire complex of local inflammatory reactions, but the effect of it is weaker than the interleukin-1 or TNF-α. However, it does not increase the products of other cytokines, but on the contrary, inhibits it, thus combining opposite properties of pro- and anti-inflammatory cytokines.

The necrosis factor α is produced in the body mainly by cells of the monocytic-macrophage system. This cytokine has a fairly wide range of activity. It is the first to appear in the blood after induction of inflammation (among all pro-inflammatory cytokines). Its action is similar to interleukin-1 effects, however, is more pronounced. It also enhances the expression of adhesion molecules, the synthesis of various inflammation factors accelerates the movement of leukocytes and activates them. In addition, it enhances the bacterial potential of phagocytes and stimulates the growth and development of fibroblasts. With an elevated local concentration of FNF-α, tissue damage occurs, and with an increase in its concentration in the blood, severe toxic effects are developing.

Anti-inflammatory cytokines

Along with the existence of factors causing an inflammatory response, cytokines are produced in the human body, which are capable of suppressing it. The relationship between them is an important moment of regulation of the emergence and development of inflammation, because not only the course of the pathological process depends on this, but also its outcome. The main representatives of this group of cytokines are:

interleukin-4;
interleukin-10;
interleukin-13;
transforming beta growth factor.

Interleukin-4 is produced by T-HELLER 2 type. It is an antagonist of γ-interferon, suppresses the secretion of TNF-α, interleukin-1, interleukin-6 and inhibits the activity of macrophages and T-lymphocytes. Together with other cytokines, he contributes to the proliferation of tissue basophils.

Also, T-helpers 2 types are produced by interleukin-10 and 13, which reduce the synthesis of cytokines responsible for the development of inflammation, and enhance the proliferation of the fat cells and in-lifocytes. As a result, cellular immunity is oppressed and humoral (antibody production) is stimulated.

Transforming beta growth factor is synthesized various types cells, including macrophages and lymphocytes. The main function is considered to suppress the activity and growth of T-lymphocytes, as well as macrophages, neutrophils, natural killers. It oppresses the immune response and stimulates the reparative processes in the body by increasing collagen synthesis.

Conclusion

Interleukin 13 - cytokine, which causes the oppression of the inflammatory process.

The role of cytokines in the body is very large. Considering their diverse regulatory properties, it becomes clear that the insufficient or excessive secretion of these substances is important in various diseases and pathological processes. Currently, drugs are developed on the basis of cytokines and their receptors, which are used in oncology, transplantology and other sectors of medicine.

Chapter 1 Literature Review

1.1. About inflammatory cytokines

1.2. Interleukin-1 in the processes of local 20 inflammation and healing of wounds

1.3. Study of the role of cytokines during chronic 25 rhinosinum

1.4. Cytokines with inflammatory processes in 31 lungs

1.5. Products of cytokines in almonds at 41 inflammation

1.6. The role of cytokines with Helicobacter 46 Pylori infection

1.7. Regulation of the functions of neutrophils by cytokines

1.8. Regulatory role of cytokines during healing 59 wounds

Chapter 2 Materials and research methods

2.1. Immunological methods

2.2. Methods of experimental study 90 actions of the ointment form 1 (3 on mice

2.3. Microscopic research methods

2.4. Characteristics of groups of patients, Application techniques 11.-1 (3 and obtaining biological material for research

Features of cytokine products for purulent-inflammatory processes in humans, cytokine products in the gastric mucosa in children with an infection of N. Rush Study of the influence of 1I-1R for healing of wounds in experiments in mice

Study of the local action of 1I-1R in patients with chronic wounds

Study of the mechanisms of action of 1 (10 in chronic purulent rhinosinus

Study of the mechanisms of action of 1 / 1p in patients with abscesses and phlegmon

Discussion of results Conclusions

Recommended list of dissertations

Analysis of the immunostimulating effect of interleukin-1Bet under local application in humans 1998, Candidate of Biological Sciences Varyishin, Elena Anatolyevna
Recombinant interleukin-1 \\ Nb (beta-leukein) in the treatment of rhinosinusitis with a protracted and chronic flow 2004, Candidate of Medical Sciences Mashko, Pavel Nikolaevich
Clinical and Immunological assessment of the effectiveness of local immunocorrection in the complex treatment of purulent-inflammatory diseases of the maxillofacial region 2009, Doctor of Medical Sciences Latyushina, Larisa Sergeevna
New aspects of pathogenesis, clinics, diagnosis and treatment of purulent inflammatory diseases of the appendages of uterus 2003, Doctor of Medical Sciences Kurbanova, Jamil Fazil Kizzy
The use of local immunocorrection in combination with ultrasonic cavitation in the treatment of children with purulent-inflammatory diseases of soft tissues 2004, Candidate of Medical Sciences Medvedev, Alexey Igorevich

The dissertation (part of the author's abstract) on the topic "Processing cytokines in the regulation of inflammation and repair processes"

Relevance of the topic

The study of the role of pro-inflammatory cytokines in an immune and inflammatory response is an important direction of modern immunology. The interactions between different types of cells ensure the stability of the body tissues in the normal place and determine the outcome of pathological processes. An important role in maintaining normal tissue homeostasis and cytokines play in inflammation. Pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF-A), are produced in response to the introduction of pathogens and tissue damage, and stimulate the development of a local inflammatory reaction, which is aimed at eliminating the pathogen and tissue healing (Dinarello S.A., 2000; Werner S., Grose R., 2003). Interleukin-8 (IL-8) (SKS-Chemokin) is the main chemoattractant for neutrophils, which first appear in the focus of inflammation and are responsible for elimination of microorganisms. In the case when local inflammation is inefficient, these mediators are produced in tissues in large quantities, appear in circulation and activate a sharp phase response or inflammatory response. That is why the close attention of researchers attracts the study of the role of pro-inflammatory cytokines, primarily in the regulation of the local inflammatory process, and then tissue regeneration.

Among pro-inflammatory cytokines, IL-1 is considered the most important mediator of the development of inflammation. It has a wide range of biological activity and stimulates the functions of almost all cells involved in protective reactions, including cells of central nervous, endocrine and hematopoietic systems. The IL-1 effect can be implemented both on the system and at the local level. An important role of IL-1 in the inflammation phase is confirmed by the fact that the expression of mRNA and levels of products of IL-LA proteins and IL-IP are rising in the early stages of wound healing (Grellner W., 2002; SATO Y., Ohshima T., 2000). In this regard, the first manifestations of biological action IL-1 are reduced to the activation of local protective reactions. The experimental introduction of IL-1 in the skin causes redness, swelling and infiltration by tissues by leukocytes. Since almost all organism cells have receptors to IL-1, this cytokine very quickly activates almost all types of cells involved in the formation of a local inflammatory response.

Important biological functions of IL-1 were a prerequisite for its use as a drug. Several attempts to use IL-LA and IL-1 (3 to restore bone marking blood-forming in cancer patients after high doses of chemotherapy (Herschanovich MA et al., 2000). Systemic use IL-1 in these studies had a positive clinical action. , but was limited due to the side effects of the introduction of IL-1 in humans, since the therapeutic dose and toxic were close. In addition, IL-1 can be introduced locally, directly into the inflammatory hearth to activate local protective mechanisms and avoid unwanted witness of sharp-phase Answer. It is of great interest in the disclosure of possible local action mechanisms IL-1. In this regard, this work is relevant and has not only theoretical, but also practical importance.

Purpose of work:

The study of the mechanisms for regulation by cytokines of local inflammatory processes and wound healing in experimental models on animals and in humans.

Tasks of work:

1. Investigate the peculiarities of pro-inflammatory cytokines in a number of purulent inflammatory processes and their connection with the functional activity of neutrophils and the peculiarities of the subpopulation composition of lymphocytes in peripheral blood.

2. Immunohistochemia methods to investigate the products of pro-inflammatory cytokines in the gastric mucosa in children with chronic gastroduodenal diseases in N.Ru1on infection.

3. Explore the wound gas in the ointment of the recombinant 1-° C of the person on the model of complicated wounds in mice. Assess the parameters of the immunity of animals with the local application of the ointment form 1P-1R. To carry out an ultrastructural analysis of the formation of the epithelium, to evaluate the expression of proteins of dense contacts of Okoothin, 7.01 and Claudine-1 immunohistochemical methods.

4. Examine the invalid effect of the ointment of the recombinant 1-α-1p person in patients with long-term non-heating wounds and trophic ulcers. Investigate changes in the cytological pattern and the functional activity of neutrophilic granulocytes in the wound focus under the action of 1 (1p.

5. Investigate the mechanisms of therapeutic action of a recombinant 111-f of a person under local use in patients with purulent-inflammatory processes, estimate its effect on the content of cytokines in the focus of inflammation, on the cytological picture and on the comparative dynamics of immunity indicators in the focus of inflammation and in peripheral blood.

Scientific novelty of work

The study shows the presence of the relationships of local production of cytokines 1 (1a, 1, 1P, 1I-8, and the activity with inflammation activity, as well as the severity of the disease in patients with purulent-inflammatory diseases (abscesses of the lungs, the epipherable of pleura, phlegmon, ChLL). For the first time it was established that in children with lymphoproliferative syndrome Local products 1I-1A, 1I-1R,

1I-6 and 1 (8 in the tissue of pharyngeal almond differ significantly in viral and bacterial infections.

For the first time, a comprehensive assessment of the immune status was carried out in individuals with HGGS and the presence of changes expressed in increasing the number of NWAP, Sat 16 and Sat 19 lymphocytes, an increase in the spontaneous products of 1 (8 and a decrease in the induced production of 1--1 (3 and 1) Blood, appearance high levels 1I-1 | 3, 1I-6 and 1I-8 in the contents of the maxillary sinuses.

The relationship between the increase in the production of 1-1 -1 | 3 and 11, -8 in the gastric mucosa and the presence of an N.R1E infection in children with chronic gastroduodenal diseases.

It was shown for the first time that the oxidic dosage form for local application, containing recombinant 1l, -1p of a person, enhances the healing of the wounds in experiments on mice, which manifests itself in a decrease in the size of the wound and is carried out by increasing the number of cells in granulation tissue, the enhancement of epithelization, which is due, Including the acceleration of cell differentiation processes in the epidermis, as well as the formation of the epidermal barrier.

The work was first studied by the mechanisms of immunostimulating actions of recombinant 1-pm under the local application for the treatment of purulent-inflammatory diseases (abscess of light, chronic purulent rhinosinusitis, phlegmons of the maxillofacial region), and the effect of the oil form of 1I-1r for repairing long-lasting wounds and trophic Yazv Lower limbs in humans.

Theoretical and practical significance

Theoretical significance is due to the fact that the work expanded on the participation of pro-inflammatory cytokines in the processes of local inflammation and reparation. The characteristics of the immune status are described, including cytokine products, as well as the state of the phagocytic system, leading to violations in the flow of the inflammatory process and wound healing. It is proposed to use an exogenous recombinant 11, -1 (3 people, which is brought directly to the lesions directly. It was revealed that 1 (1 (3 plays a key role in the processes of local inflammation and healing of wounds in animal experiments and in humans.

The value of the results of the research results for practice is confirmed by the fact that the method of treating damage to the mucous membrane of the gastrointestinal tract (patent for the invention No. 2 2355415 dated January 10, 2009), composition for the treatment of damage to the mucous membrane of the gastrointestinal tract (patent for the invention № 2361606 dated January 10, 2009), interleukin-containing composition (patent for the invention No. 2432170 of 10.10.2010).

Based on the results obtained, the importance of determining the local cytokine products in the focus of inflammation to assess the characteristics of the inflammatory process is revealed. The informativeness of the Method of immunohistochemia is shown to study the products of cytokines in inflammatory processes in the tract and respiratory tract.

It is shown that 1 (3 (3 has wound-healing and local immunostimulating activity, possible mechanisms of cytokine action are disclosed.

Implementation of work results in practice

The results were introduced into practical health care in the Federal State Budgetary Institution "SPB Research Institute of ENT" MH of Russia, St. Petersburg, in the clinic of the Toracal Surgery of the Military Medical Academy. CM. Kirov, St. Petersburg; In the center of treating surgical infections, St. Petersburg, the Baltic Clinical Central Basin Hospital. Mushanovsky, St. Petersburg, in the clinic of maxillofacial and plastic surgery SPbGMU. Pavlova, St. Petersburg.

The results of the dissertation work can be used in the research institutes involved in the study of cytokines: the FGBU "SSC" Institute of Immunology "FMBA of Russia, Moscow, Military Medical Academy. CM. Kirov, St. Petersburg, FSBI "Research Institute of Experimental Medicine" SZO RAMN, St. Petersburg and others.

Basic provisions endured for protection) 7

1. The levels of pro-inflammatory cytokines in the focus of inflammation reflect the features of the flow of inflammatory processes (activity, prevalence of the process, the presence of infection) in humans.

2. With purulent-inflammatory diseases, a person has a decrease in the functions of neutrophils in the focus of inflammation, these violations make it difficult to resolve inflammation.

3. The use of an ocean form containing a recombinant person enhances healing of wounds in an experimental model in mice. Under the action of 1 (3 (3, the size of the wounds occurs, the number of cells in granulation tissue increases and epithelization is enhanced.

4. Local therapy With the use of an ointment form containing recombinant 1I-1 (3 people, there is no action on such parameters as the leukocytar composition of peripheral blood, the size of the spleen and the amount of splenocytes in the experiments on mice.

5. The use of an ointment form containing recombinant 1I-1 | 3 people, in patients with long-term non-heating wounds and trophic ulcers of lower extremities activates neutrophilic granulocytes, and also causes an increase in the relative amount of macrophages and connective tissue cells in the wound focus.

6. The local application of recombinant IL-1 (3 people increases the local protection factors in the focus of inflammation in patients with purulent-inflammatory diseases. IL-IP operation mechanisms are associated with increasing product cytokines and stimulation by their account of neutrophil functions. Action IL- IP under local use in humans is limited to an inflammatory hearth.

Personal contribution of the applicant is to participate in all stages of the fulfillment of the dissertation research; conducting the analysis of the state of the issue according to modern literature; statistical data processing; interpretation of the results obtained; preparation of basic publications for the work performed. Cytological studies, evaluation of bactericidal, phagocytic functions of neutrophils, immunohistochemical study of cytokine products, histochemical studies, assessment of lymphocyte subpopulations by the method of flow cytometry with HGGS is made by the author. Experimental animal studies were performed by the author together with co-authors of work.

Approbation of work

The main results of the dissertation work are reported at Russian and international conferences: the National Congress on Diseases of Breathing Bodies (6th, Novosibirsk, 1996, 13th, St. Petersburg, 2003, 16th, G. St. Petersburg, 2006), 2nd Joint Meeting of The Ics and Isicr (Jerusalem, 1998), a scientific conference with international participation. Acad. V.IOffe "Days of Immunology in St. Petersburg", (St. Petersburg, 2nd, 1998; 3rd, 1999; 5th, 2001; 6th, 2002; 7th , 2003; 11th, 2007,), 4th World Congress On Inflammation (Paris, France, 1999), 2nd Congress of Immunologists of Russia (Sochi, 1999), 5th World Congress on Trauma, Shock, Inflammation And.

Sepsis - Pathophysiology, Immune Consequences and Therapy (Munich, 2000), Euroconference on molecular aspects of the initiation and regulation of immune response "Communication within the immune system" (San Feliu de Guixoils, 2001), European Respiratory Society Annual Congress (12th, Stockholm, 2002; 17th, Stockholm, 2007; 19th ", Vienna, 2009; 21st, Amsterdam, 2011), 10th All-Russian Scientific Forum" St. Petersburg - Gastro "(St. Petersburg, 2008), 8- Congress "Modern problems of allergology, immunology and immunopharmacology" (Moscow, 2007), United Immunological Forum (St. Petersburg, 2008), 1st Congress of the Russian Society of Gastroenterological Surgeons "Actual Issues of Surgical Gastroenterology", (Gelendzhik, 2008), Interregional Forum "Actual Questions of Allergology and Immunology - Interdisciplinary Problems" (St. Petersburg, 2010), Interregional Forum "Clinical Immunology and Allergology - Interdisciplinary Problems" (Kaz An, 2012).

Publications

The main results of the thesis was published in 71 printed work, of which 21 article in journals recommended by the WAK of the Russian Federation to publish materials of doctoral and candidate dissertations ("EUROPEAN CYTOKINE NETWORK", "Immunology", "Herald of Surgery", "Russian Immunological Journal" ("Russian Journal of Immunology ")," Cytokines and inflammation "," Medical Immunology "," Breast and Cardiovascular Surgery "," Russian otorinolaryngology "," Journal of Microbiology, Epidemiology and Immunobiology "), 6 articles in scientific journals, 40 publications in Materials of scientific congresses and conferences, one chapter in the book, three patents.

Structure and scope of the dissertation

The work consists of introducing, literature review, descriptions of materials and methods, six chapters presentation of research results, discussion of results and literature. The dissertation is set out on 256 pages, includes 20 tables and 30 drawings. The list of cited literature consists of 368 sources, of which 62 domestic and 306 foreign.

Similar dissertation works by the specialty "Immunology", 03.03.03 CIFR WAK

The role of secretory neutrophil products in the regulation of local inflammation and immunity reactions 2005, Tretyakova, Irina Evgenievna
Clinical and Immunological Justification of the local application of recombinant interleukin-1 "beta" and interleukin-2 in the treatment of acute purulent sinusits 2003, Candidate of Medical Sciences Katinas, Elena Borisovna
Pathophysiological aspects of surgical infection and optimization of approaches to its treatment 2005, Namokov, Evgeny Vladimirovich
Pathogenetic substantiation of sorption-appliquational therapy of purulent wounds 2005, Candidate of Medical Sciences Kryukova, Victoria Viktorovna
Factors of immunity system in patients with dysplastic changes of bronchial epithelium and lung cancer 2006, Candidate of Medical Sciences Gerdt, Lyubov Viktorovna

Conclusion of dissertation on the topic "Immunology", Varyishin, Elena Anatolyevna

210 Conclusions

1. With purulent-inflammatory diseases, a person has a significant decrease in the functional activity of neutrophils in the focus of inflammation, the cytological picture is characterized by a predominance of neutrophils and a decrease in the share of macrophages and lymphocytes. There is a local increase in the products of pro-inflammatory cytokines 11.-1 A, II.-10, 11.-6, 11.-8 and the same with increasing activity, the severity of the inflammatory process, as well as in the presence of a bacterial infection.

2. Strengthening products 11.-10 and 11. -8 in the gastric mucosa is an N. Rruklu infection marker in children with chronic gastroduodenal diseases.

3. When applying the ointment form of recombinant 11. -1-10 person in experiments, mice decreases the size of wounds of leather, increasing the number of cells in granulation tissue and increased epithelization. Appliques of the ointment form 1I-10 in experimental studies do not affect the weight of the body, the weight of the spleen, the amount of splenocytes and the leukocytar composition of the peripheral blood in mice.

4. The use of the ointment form of recombinant 11.-10 people in patients with long-term non-heating wounds and trophic ulcers of lower extremities stimulates phagocytic and bactericidal functions of neutrophilic granulocytes, and also causes an increase in the number of macrophages and connective tissue cells in the wound fire.

5. Local use of recombinant 11.-1 (3 people with purulent-inflammatory processes stimulates the functional activity of neutrophils (chemotaxis, phagocytosis, bactericidal function), causes an increase in levels of 1 s-8, 11.-6, as well as an increase in synthesis 11.-1a , 11.-8 and the same leukocytes in the focus of inflammation. Under the local application of 11. -0, with purulent-inflammatory diseases, a person does not have any influence on the functions of neutrophils and cytokine products in peripheral blood.

6. Mechanisms of immunostimulating actions 1I | 3 under local application are associated with the stimulation of the synthesis of pro-inflammatory cytokines and the activation of the functions of neutrophils in the focus of inflammation in humans.

The definition of cytokine products in the focus of inflammation can serve as a marker of the peculiarities of the inflammatory process. The immunohistochemistry method is informative for studying local cytokine products in diseases of the gastrointestinal tract, as well as inflammatory processes in the upper and lower respiratory tract. The results of the study of cytokine products can serve as a basis for individual selection of therapy.

The recombinant 1-α-1r person can be used as a healing preparation in the form of a solution for therapy of chronic purulent inflammatory processes. The use of an ointment form containing 1I-1p is a promising direction for the treatment of long-lasting wounds and trophic ulcers of various etiology in humans.

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