UDC 612.017.11: 616.98-092: 578.828.6: 615.37 O1

PROPERTIES AND ROLE OF ALPHA TUMOR NECROSIS FACTOR IN PATHOGENESIS

HIV INFECTION

Pavel Dmitrievich Dunaev *, Sergei Vasilievich Boychuk, Ilshat Ganievich Mustafin Kazan State Medical University

The review presents the current understanding of the tumor necrosis factor alpha: its origin, receptors, basic properties, as well as its role in the pathogenesis of HIV infection (infection caused by the human immunodeficiency virus). Tumor necrosis factor alpha induces viral replication in CD4 + T-lymphocytes, monocytes and macrophages, promotes the death of uninfected CD4 + T-lymphocytes, as well as CDS * by the apoptosis mechanism, which ensures the progression of immunodeficiency. Tumor necrosis factor alpha maintains the viability of infected CD4 * T-lymphocytes, contributing to the formation of a virus reservoir in the body of the diseased organism. An increase in the content of tumor necrosis factor alpha in the blood plasma of HIV-infected patients should be considered as a marker of disease progression.

Key words: tumor necrosis factor alpha, viral replication, lymphocyte apoptosis, HIV infection.

THE PROPERTIES AND ROLE OF TUMOR NECROSIS FACTOR ALPHA IN THE PATHOGENESIS OF HIV INFECTION P.D. Dunaev, S.V. Boychuk, I.G. Mustafin. Kazan State Medical University, Kazan, Russia. This review presents the current understanding regarding the tumor necrosis factor alpha: its origin, receptors, main properties and its role in the pathogenesis of HIV infection (the infection, caused by the Human Immunodeficiency Virus). Tumor necrosis factor alpha induces viral replication in CD4 + T lymphocytes, monocytes and macrophages, promotes death of uninfected CD4 + T lymphocytes as well as CD8 + by the mechanism of apoptosis, allowing the progression of immunodeficiency. Tumor necrosis factor alpha maintains the viability of infected CD4 + T lymphocytes, contributing to the formation of the viral reservoir in the patient. Elevated levels of the tumor necrosis factor alpha in the blood plasma of HIV-infected individuals should be regarded as a marker of disease progression. Keywords: tumor necrosis factor alpha, viral replication, lymphocyte apoptosis, HIV infection.

Tumor necrosis factor alpha (TNFa, in the English-language literature TNFa - from tumor necrosis factor alfa) was described in 1975. It was isolated from the blood serum of laboratory mice and induced tumor necrosis (fibrosarcoma) in these animals (hence its name).

TNFa is a glycoprotein with a molecular weight of 17.4 kDa. The structure of this molecule is homologous to TNFr, nerve growth factor, Fas ligand, membrane molecules CD30 and CD40, which unites them into a common superfamily of TNF proteins (Tumour Necrosis Factor superfamily).

TNFα-producing cells are: (1) leukocytes, including monocytes / macrophages, basophils, neutrophils, T-lymphocytes (T-Lf) - activated CD4 + and CD8 +, as well as NK cells (natural killer cells, from the English Natural Killer), LAK cells (cytokine activated NK cells); (2) other types of cells - endothelial, mast, dendritic cells, fibroblasts, cardiomyocytes, stromal cells of the red bone marrow, neuroglia cells, adipose tissue cells (adipocytes). It should be noted that the predominant producers of this cytokine are activated macrophages and T-Lf.

There are two types of TNFα receptors: type 1 (TNF-R1, p55, CD120a) and type 2 (TNF-R2, p75, CD120b). TNF-R1 predominates, through which TNFa carries out most of its biological effects.

Correspondence address: [email protected] 290

fects. The interaction of TNFa with TNF-R1 or TNF-R2 on the surface of the target cell can lead to different consequences.

First, the induction of target cell apoptosis is possible. It was shown that the cytoplasmic part of the TNF-R1 receptor molecule contains the TRADD (TNFR-Associated Death Domen) “death domain”, which is also present in the Fas receptor. The TRADD domain transmits a signal from TNF-R1 to the target cell. To start the apoptosis program, a signal from this domain must arrive at FADD (Fas-Associated Death Domain) and RIP (Receptor Interacting Protein) molecules. These proteins activate specific enzymes caspase-protease FLICE (FADD-Like IL-1b-Converting protein) and endonucleases (DNases I and II), which leads to deoxyribonucleic acid (DNA) cleavage and subsequent death of the target cell. It has been shown that the binding of TNF-a to the membrane receptor TNF-R2 of the target cell is also capable of inducing its apoptosis. In this case, the inactivation of TRAF2 molecules (TNFR-Associated Factor) occurs. TRAF2 molecules support the activity of cellular Inhibitor of Apoptosis Proteins (cIAP).

Secondly, the opposite situation is possible - the induction of a cascade of enzymatic reactions (with the participation of the nuclear transcription factor NF-cr, AP-1 protein, MAPK protein kinase, and other proteins), leading to cell activation and blocking the development of apoptosis by its inhibitors Bcl-2 and c-FLIP.

Factors that determine the cell's response to

TNFa, remain controversial. The microenvironment of the cell plays an important role. In particular, in HIV infection, viral proteins promote TNFa-mediated apoptosis of T-Lp CD4 + and CD8 + (see below).

Participation in the implementation of the inflammatory response

TNFa is synthesized in the focus of acute inflammation by T-Lf and B-Lf, NK cells, monocytes / macrophages. It induces the activation of neutrophils and macrophages, as well as their chemotaxis. In macrophages, under the influence of TNF-a, the synthesis of growth factors (colony-stimulating factor of granulocytes and monocytes, colony-stimulating factor of monocytes), interferon y, interleukins (IL-1, IL-8), prostaglandins (PGE2) increases. Together with IL-1 and IL-6, TNF-a induces the synthesis of acute-phase proteins (such as C-reactive protein, fibrinogen, ceruloplasmin, etc.) by the cells of the mononuclear phagocytic system of the liver. The described effects of TNFa have a protective effect, since they promote phagocytosis of pathogenic microorganisms by activated neutrophils and macrophages. In addition, C-reactive protein is able to bind and neutralize bacterial endotoxins and immune complexes, and, being an opsonin, facilitates bacterial phagocytosis.

TNFa, IL-1 and IL-6 are secondary (leukocyte) pyrogens. They penetrate the blood-brain barrier with the bloodstream and interact with the neurons of the hypothalamic thermoregulation center, which leads to the development of fever.

TNFa in a physiological concentration is able to increase the permeability of the vascular wall, which contributes to damage to endothelial cells, thrombosis, and the formation of hemorrhagic necrosis.

Some authors provide data on the participation of TNFa in the formation of a chronic inflammatory process. In particular, it was demonstrated that in the lungs of rats, an increased concentration of TNFα causes a severe inflammatory process with the development of interstitial fibrosis. TNF-a inactivation has been proposed as a pathogenetic therapy for patients with idiopathic pulmonary fibrosis.

Involvement in the immune response

TNFα induces the migration of dendritic cells that have taken up antigenic material to the lymph nodes and their further maturation. During maturation, these cells develop specific membrane bone-mutating molecules CD80 / 86, which allow them to perform their main function - to present captured antigens in conjunction with molecules of the major histocompatibility complex (MHC - from the English Major Histocompatibility

Complex) class I or II lymphocytes (T and B) and initiate the development of an immune response. TNFα is able to induce the activation and proliferation of T-Lf.

At the same time, works of recent years show that TNFα is also capable of exerting the opposite effect - inducing tumor development, promoting proliferation and angiogenesis. TNF-a receptors express cancer cells of the stomach, liver and pancreas, colorectal cancer, melanoma, lung carcinoma, etc. Increased expression of TNF-a receptors in tumor cells in most cases is an unfavorable prognostic sign. In this regard, the use of monoclonal antibodies against TNFα and its receptors for the treatment of malignant tumors can be considered a promising direction.

Metabolic effects

TNFa inhibits the activity of lipoprotein lipase in adipose tissue cells (adipocytes), which leads to disruption of fat deposition (lipogenesis) in them. This effect can contribute to the depletion of the body - cachexia (TNFa was previously called cachexin).

Role of TNFa in the pathogenesis of HIV infection

The synthesis and secretion of TNFa by infected CD4 + T-Lf, monocytes and macrophages increases with the progression of HIV infection. Virus proteins (for example, surface glycoprotein gp120) induce the synthesis of TNFα.

As the amount of T-Lf CD4 + decreases in the patient's blood plasma, the TNFa content increases, which inversely correlates with the content of viral ribonucleic acid (RNA) in the plasma. For this reason, an increase in the concentration of TNFa in the plasma of HIV-infected is considered as a marker of disease progression.

TNFα induces HIV-1 replication in

T-Lf CD4 + due to their activation. When activated on the membrane, T-Lf CD4 + increases the expression of CXCR4 molecules, which promotes the penetration of the virus into these cells. Then, using nuclear transcription factors (in particular, NF-kR), the activity of which is increased, the virus replicates itself. TNFα, binding to TNF-R1, induces HIV-1 replication in infected monocytes and macrophages. The replication mechanism is also associated with the activation of these cells under the influence of TNFα.

After binding to any of its receptors, TNFα causes apoptosis in uninfected CD4 + T-Lp, as well as CD8 + in HIV-infected individuals. It has been demonstrated that the HIV-1 surface envelope glycoprotein gp120, by binding to the CXCR4 coreceptor on the surface of CD8 + T-Lf, induces increased expression of TNF-R2 receptors in them. This increases the sensitivity of these cells to TNFa-mediated apoptosis. The apoptosis program is triggered after the contact interaction of CD8 + with macrophages, on the membrane of which TNF-a molecules are fixed. In addition, viral gp120 itself is capable of triggering the programmed death of CD8 + T-Lf by binding to TNF-R1 on their membrane. It has been shown that TNF-a-mediated apoptosis of uninfected CD4 + T-Lf is also carried out by similar mechanisms. Our own studies have shown that in the presence of this cytokine, mainly uninfected CD4 + T-Lf perish by the apoptosis mechanism, while infected cells remain viable in culture. Literature data indicate that the viability of infected CD4 + is provided by HIV-1 proteins. The Nef virus protein inactivates the intracellular apoptosis inducer protein Bax. The viral Tat protein increases the activity of the apoptosis inhibitor protein c-FLIP in the cell. At the same time, as our studies have shown, TNFa itself is involved in this process. Acting together with viral proteins, it determines the level of activation that is optimal for the vital activity of those infected with T-Lf CD4 + (cells with viral replication have, in contrast to uninfected CD4 + cells, minimal expression of activation markers). These features prevent the development of activation apoptosis in HIV-infected T-Lf CD4 +.

Thus, it can be concluded that TNFα plays a negative role in the pathogenesis of HIV infection. It promotes further infection of immunocompetent cells, as well as viral replication. TNFα induces the death of uninfected CD4 + and CD8 + T-Lp via the apoptosis mechanism, which ensures the progression of immunodeficiency. TNFa maintains the vitality of infi-292

cited T-Lf CD4 +, thereby contributing to the formation of a reservoir of HIV-1 in the patient's body. Consequently, an increase in plasma TNFa levels in HIV-infected patients should be considered as a marker of disease progression.

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Scientific editor: M. Merkusheva, PSPbGMU im. acad. Pavlova, general medicine.
September 2018.

Synonyms: Tumor necrosis factor, TNF, Tumor necrosis factor - alpha, TNF-alpha, сachectin.

General information

Tumor necrosis factor (TNF) is believed to be an important component in killing cancer cells. This protein (or a combination of them) triggers the body's immune response to any external stimulus, be it inflammation, infection, injury, or tumor.

The TNF test allows you to determine the presence and / or stage of cancer or other systemic disease and select an effective treatment strategy.

For the first time, this component was found in the blood of laboratory mice after a complex of routine inoculations.

TNF plays a role in the development of:

• autoimmune diseases (rheumatoid arthritis),
• ischemic brain damage,
• multiple sclerosis,
• dementia in AIDS patients,
• is considered one of the important markers of damage to the liver parenchyma in hepatitis C, etc.

Methods are being developed for the use of monoclonal antibodies to TNF for the treatment of sepsis, inflammatory diseases and tumors.

TNF is a hormone-like protein (cytokine) that is produced by white blood cells - white blood cells. It interferes with the metabolism of fats and carbohydrates and causes exhaustion and cachexia in patients with tumors and long-term infectious diseases, affects blood coagulation processes, is responsible for the functioning of endothelial cells (cells lining the walls of blood vessels from the inside), etc. activates the production of proteins of the acute phase of inflammation in the liver, enhances the flow of T- and B-lymphocytes from the bone marrow into the blood and migration to the inflammatory focus, plays a major role in the development of sepsis and septic shock.

There are 2 types of TNF: alpha and beta.

• TNF-alpha is rarely detected in the blood of a healthy person, only in the case of penetration of pathological microorganisms, poisons. The response time of the body is about 40 minutes, and after 1.5-3 hours the concentration of TNF-alpha in the blood serum reaches its peak.
• TNF-beta is detected in the blood only 2-3 days after contact with the antigen (irritant).

The biological effect of TNF depends on its concentration: at low concentrations it acts mainly at the place of production, in medium concentrations, entering the bloodstream, acts as a hormone, exerting a pyrogenic effect, stimulating the formation of phagocytes, enhances blood coagulation, reduces appetite, in high concentrations it can lead to sepsis.

TNF, together with other cytokines, plays a central role in the development of neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Activated neuroglial cells begin to synthesize TNF, trigger inflammation in the central nervous system and the destruction of neurons.

TNF in oncology

Experiments with mice made it possible to establish the dependence of the oncological process on the concentration of TNF in the body - the higher its level, the faster the cancer tissues die. Tumor necrosis factor activates special receptors that define a malignant cell, block its further division and contribute to its death (necrosis). TNF acts in the same way on cells infected with viruses and other pathogenic microorganisms. At the same time, the surrounding healthy tissues are not involved in the process of destroying pathological cells.

In addition to the fact that TNF has a pronounced cytotoxic (antitumor) effect, this protein:

• participates in the self-regulation of the immune system, activates the defenses;
  • responsible for the following processes in the body:
  • migration (movement) of immunity cells (leukocytes);
  • apoptosis (breakdown and death of malignant cells);
  • blocking angiogenesis (the formation and proliferation of tumor blood vessels);
• can affect cancer cells that are resistant to chemotherapy drugs.

The TNF test is to determine the concentration of the alpha form of the protein in the serum. The disadvantage of this technique is its low specificity, i.e. the inability to establish a specific pathology. Therefore, making an accurate diagnosis requires a number of other laboratory tests (general blood and urine analysis, CT, ultrasound, ECG, X-ray, etc.).

Indications for analysis for TNF

A doctor may prescribe this test to assess the general state of the immune system in case of regularly recurring systemic diseases and recurrence of autoimmune pathologies.

Also, this examination is quite informative in the diagnosis of the following diseases:

• chronic lung disease;
• burns and injuries;
• connective tissue pathology;
• cancer processes;
• atherosclerosis of the vessels of the brain and heart, coronary artery disease (CHD), chronic heart failure;
• autoimmune disorders (scleroderma, systemic lupus erythematosus, etc.);
• acute pancreatitis (inflammation of the pancreas);
• liver damage (alcohol intoxication), damage to its parenchyma in hepatitis C;
• septic shock (complication of infectious diseases);
• endometriosis (proliferation of tissues of the inner walls of the uterus);
• rejection of an implant or graft after transplant;
• neuropathies (pathological processes in the nerves).

Which doctor prescribes the analysis

Gives direction for analysis and deciphers the results

• oncologist,
• infectious disease specialist,
• immunologist,
• general doctor.

Norm for TNF

Important! Rates vary depending on the reagents and equipment used in each specific laboratory. Therefore, when interpreting the results, it is necessary to use the standards adopted in the laboratory where the analysis was submitted.

However, in modern laboratories, the value is considered the norm

It should be borne in mind that this indicator is studied in dynamics, i.e. several tests need to be done to get reliable results.

Important! The interpretation of the results is always carried out in a complex manner. It is impossible to make an accurate diagnosis based on only one analysis.

TNF increased

An excess of the TNF norm is most often observed in the following conditions:

• the presence of infectious and viral diseases (endocarditis, hepatitis C, tuberculosis, herpes, etc.);
• shock after injury, burn;
• burn disease (burns from 15% of the entire surface);
• dIC syndrome (blood clotting disorder, in which there is the formation of blood clots in small vessels);
• sepsis (severe intoxication of the body with pathogenic microflora and products of its vital activity, mainly gram-negative);
• autoimmune diseases (lupus erythematosus, rheumatoid arthritis, scleroderma, etc.);
• allergic processes in the body, incl. relapse of bronchial asthma;
• rejection of the graft after transplant;
• psoriasis (non-infectious dermatosis);
• oncological processes in the body;
• multiple myeloma (a tumor of plasma cells);
• dementia against the background of atherosclerosis of the vessels of the brain;
• hemodynamic disturbances (decrease in the strength of heart contractions, high vascular permeability, low cardiac output, etc.);
• coronary atherosclerosis (damage to the blood vessels that feed the heart);
• chronic inflammation of the bronchi (bronchitis);
• collagenosis (systemic or local damage to the connective tissue);
• abscesses and inflammation of the pancreas;
• obesity;
• fungal mycosis.

High TNF in pregnant women indicates violations of intrauterine formation and development of the fetus or infection of the amniotic fluid, as well as the threat of miscarriage or premature birth.

Lowering values

A decrease in the TNF indicator is observed in the following cases:

• congenital or acquired human immunodeficiency, incl. AIDS;
• oncology of the stomach;
• pernicious anemia (violation of hematopoiesis due to vitamin B12 deficiency);
• severe infectious diseases of viral etiology;
• atopic syndrome (the patient has asthma or atopic dermatitis with an allergic rhinitis).

A decrease in the concentration of TNF can be facilitated by the intake of hormones, incl. corticosteroids, cytostatics, antidepressants, immunosuppressants, etc.

Preparation for analysis

To determine TNF, venous blood serum is required in a volume of up to 5 ml.

• Biomaterials are taken in the morning (at the peak of TNF concentration) and on an empty stomach. The last meal should be made at least 8-10 hours ago. It is also forbidden to drink any liquid other than ordinary still water.
• On the eve of blood sampling and half an hour immediately before the procedure, it is necessary to observe a rest regimen. Physical activity, sports training, heavy lifting, brisk walking, excitement and stress are prohibited.
• The test is performed prior to other laboratory tests (ultrasound, X-ray, CT, MRI, fluorography, etc.).
• It is advisable not to smoke 2-3 hours before the manipulation, and on the eve it is forbidden to take alcoholic beverages, drugs, steroids.

Alternative names: TNF-α, English: tumor necrosis factor (TNF)

TNF is actively involved in any immune response of the body, therefore its concentration depends on the intensity of the inflammatory process. Determination of the TNF concentration plays a huge role in determining the tactics of treatment in such extremely severe conditions as sepsis, autoimmune diseases, AIDS, and multiple organ failure. Also, an increase in the change in the level of this indicator is in direct proportion to the severity of chronic heart failure and bronchial asthma.

Material for research:

Venous blood in a volume of 3-5 ml. The analysis uses blood serum obtained by centrifuging whole blood.

Research method:

Linked immunosorbent assay.

Preparation for analysis

No special training required. Food regimen, emotional and physical stress do not affect the level of the indicator. It is recommended to donate blood in the morning on an empty stomach.

Indications for determining the level of TNF

TNF determines to some extent the pathogenesis of severe pathological conditions. At international conferences, which are based on national recommendations for laboratory diagnostics.

General indications were determined to determine the level of this indicator:

• study of the immune status of patients with severe acute, chronic infectious and autoimmune diseases;
• oncopathology;
• atherosclerotic lesions of the vessels of the heart and brain;
• rheumatoid arthritis;
• systemic lupus erythematosus and scleroderma;
• chronic bronchopulmonary diseases.

Reference values \u200b\u200band interpretation of results

According to national guidelines for laboratory diagnostics, normal TNF levels are considered 0-50 pg / L (picograms per liter). In most laboratories, it is customary to measure the amount of TNF in picograms per milliliter. In this case, the reference level is between 0 and 8.2 pg / ml.

An increase in TNF levels is observed in the following pathological conditions:

• sepsis;
• disseminated intravascular coagulation syndrome;
• severe infectious diseases - endocarditis, recurrent herpes, hepatitis C;
• severe shock;
• autoimmune and allergic diseases;
• ischemic heart disease, manifested by heart failure;
• chronic bronchopulmonary diseases;
• psoriasis;
• collagenoses;
• atherosclerosis of the coronary arteries and cerebral arteries;
• oncopathology;
• graft rejection reaction.

Features of this analysis

Studying the level of the indicator in dynamics is of great importance. A decrease in TNF concentration as the disease progresses speaks in favor of stabilization of the patient's condition and an increase in the likelihood of a positive outcome.

Conclusion

Determination of the level of TNF plays a role in determining the prognosis of the disease. On the basis of this indicator, the optimal tactics for the treatment of severe diseases is determined. Further study of the mechanisms of interaction of tumor necrosis factor with cells and tissues will allow in the future to develop more effective methods of treating sepsis and autoimmune diseases. There are emerging data on the possibility of using TNF in the diagnosis of specific oncopathology.

The disadvantage of this method can be considered low specificity, which does not allow only by determining the level of the indicator to suggest a specific pathology. Therefore, the study of TNF should be accompanied without fail by the appointment of general clinical blood tests, instrumental examination methods (ultrasound, CT, radiography, ECG).

Literature:

1. Nazarenko G.I., Kishkun A.A. "Clinical evaluation of laboratory research results", Litan, Medicine (Tatarstan), M .: Medicine. - 2000 .-- 544 p.
2. Inflammatory mediators. Acute phase proteins and their role in the development of the immune response. MGAVMiB, Moscow, 2013 .-- p. 30

Method of determination Immunoassay.

Study material Blood serum

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Regulator of immune and inflammatory reactions.

The term TNF (tumor necrosis factor) was proposed in 1975. It was named so for its main biological effect - the ability to exert a cytotoxic effect on a tumor cell in vivo. Refers to cytokines. It comes in two forms, alpha and beta. Able to induce in vivo hemorrhagic necrosis of some tumor cells without damaging normal cells. But at the same time, it causes shock if its production is caused by bacterial endotoxins. TNF-alpha is a glycoprotein with a molecular weight of 17 400 kDa. It is formed by macrophages, eosinophils and natural killers (14% of lymphocytes). In the blood serum of healthy people, TNF-alpha is practically not detected. Its level increases with infection, ingestion of bacterial endotoxins.

In rheumatoid arthritis, TNF-alpha accumulates in the joint fluid; with many inflammatory processes it is also determined in urine. Factor secretion is recorded after 40 minutes; its maximum is reached in 1.5 - 3 hours after stimulation. The half-life in the blood is 15 minutes. TNF-alpha is close to IL-1 and IL-6. But its important feature is the effect on tumor cells due to apoptosis, generation of reactive oxygen species and nitric oxide. TNF-alpha can eliminate not only tumor cells, but also cells affected by the virus. It participates in the development of the immune response, causing the proliferation of B- and T-lymphocytes and prevents the development of immunological tolerance. TNF-alpha also inhibits erythro-, myelo- and lymphopoiesis, but has a radioprotective effect.

The biological effects of TNF depend on its concentration. At low concentrations, it acts at its "birthplace" as a para- and autocrine regulator of the immune-inflammatory response against injury or infection. It is the main stimulant for neutrophils and endothelial cells, for their adhesion and further migration of leukocytes, proliferation of fibroblasts and endothelium during wound healing. At moderate concentrations, TNF-alpha, entering the bloodstream, acts as a hormone, exerting a pyrogenic effect, stimulating the formation of phagocytes, increasing blood clotting, reducing appetite, being an important factor in the development of cachexia in chronic diseases such as tuberculosis and cancer.

High concentrations, determined in gram-negative sepsis, are the most important cause of septic shock due to a decrease in tissue perfusion, a decrease in blood pressure, intravascular thrombosis, a sharp, incompatible with life, drop in blood glucose concentration.

TNF plays an important role in the pathogenesis and choice of therapy for various pathologies: septic shock, autoimmune diseases (rheumatoid arthritis), endometriosis, ischemic brain lesions, multiple sclerosis, dementia in AIDS patients, acute pancreatitis, neuropathies, alcoholic liver damage, transplant rejection. TNF is considered one of the important markers of damage to the liver parenchyma and, along with other cytokines, has diagnostic and prognostic value in the treatment of hepatitis C.

The increased level of TNF-alpha in the blood correlates with the severity of the manifestations of chronic heart failure. Exacerbation of bronchial asthma is also associated with increased production of TNF-alpha. The magnitude and dynamics of changes in TNF-alpha, in combination with IL-1b and IL-6, reflects the severity of the course of burn disease and the nature of burn healing. Methods of using monoclonal antibodies to TNF for the treatment of sepsis, inflammatory diseases and tumors are being developed. All these methods require regular laboratory monitoring of tumor necrosis factor.

Literature

1. E.L. Nasonov Tumor necrosis factor is a new target for anti-inflammatory therapy of rheumatoid arthritis // RMZh, 2000, vol. 8, no. 17.
2. Suslova T.E. et al. Proinflammatory cytokines and endothelial dysfunction in patients with coronary atherosclerosis and in persons with heredity burdened by atherosclerosis // Allergology and immunology, 2000. - volume 1. - No. 2. - P. 159.
3. Burtis C., Ashwood E., Bruns D / Tietz textbook of clinical chemistry and molecular diagnostics / 2006 / Elsevir Inc, / pp. 702 - 708.

One of a number of protein components that provoke the death of cancer cells is tumor necrosis factor. TNF itself is a multifunctional cytokine (a hormone-like protein element produced by protective cells) that affects lipid metabolic processes, coagulation and functionality of endothelial cell components lining blood vessels. These features can provoke cell death. Blockers that suppress the work of natural TNF interfere with the normal functioning of natural resistance.

Tumor necrosis factor in the elimination of oncology

These medicines belong to the targeted type of treatment. They have the following therapeutic effect:

In combination with Melphalan, it is used to eliminate sarcoma lesions of the soft tissues of the arms and legs;
... due to an increase in the dose of interleukins 1.8 and 1.6, the formation of substances that prevent the progression of the oncological focus is influenced;
... used as an auxiliary medication in neutralizing complications provoked by oncology;
... TNF antagonists are an effective treatment for people with non-melanoma cutaneous lesions (eg, basal cell carcinoma, squamous cell oncology, lymphoma).

Medicines

As a drug TNF is determined only in certain clinical trials. Today's oncology still does not have the necessary list of knowledge about these medicines. The optimal amount of the substance depends on the specific cancer situation.

Medicines for general effects are:
... Remitsad;
... Humira;
... Certolizumab;
... Golimumab;
... Mercaptopurine (used in T-cell lymphoma).

How much does the examination cost?

The validity of the use of tumor necrosis factor in the elimination of oncopathologies is determined individually with the help of analyzes. The price of this procedure depends on the completeness of the examination, the authority and technical equipment of the medical facility. institutions, indicators of other diagnostic measures. Based on this, we can say that the price fluctuates around 2-8 thousand rubles. This cost necessarily includes an immunoassay.

Indications for analysis

The collection of information about the state of natural resistance is carried out with frequent bacterial infections, prolonged inflammation, in the presence of autoimmune pathologies. Also, the check is carried out in the presence of cancer, connective tissue defects, chronic pulmonary pathologies.

Preparation for the examination

First of all, in the morning on an empty stomach, blood is donated for analysis (almost all liquids except water are prohibited before delivery). The time interval between the last meal and the test should be at least 8 hours. Even minimal physical activity is contraindicated half an hour before taking a blood sample. Blood is taken from a vein.

Indicators of TNF results

The norm is 0-8.21 pg / ml.

Excess:
... infectious pathologies such as hepatitis C;
... endocarditis of an infectious type;
... autoimmune defects;
... allergic defects (for example, bronchial asthma);
... rheumatoid arthritis;
... myeloma pathology.

Decrease:
... immune deficiency of hereditary or acquired type;
... taking medications - corticosteroids, cytostatics;
... gastric oncology;
... pernicious anemia.

The most dangerous consequences

Modern medicine uses tumor necrosis factor carefully, because certain studies have proven that it is a fundamental element in the progression of sepsis and toxic shock. The presence of this protein component stimulated the activity of bacteria and viruses. It was also revealed that TNF is part of the process in which autoimmune pathologies are formed (for example, rheumatoid arthritis), in which the natural resistance of a person takes the normal cells of the body for foreign and attacks them.

To minimize toxic effects, you need to follow these measures:
... apply the technique locally;
... combine with other medicines;
... work with proteins with minimal toxicity;
... use neutralizing antibodies during procedures.
... due to increased toxicity, it is always limited to use.

Reasons why necrosis factor does not kill a tumor

Tumor formations are able to effectively resist the body's immune defenses. In addition, the tumor itself can produce TNF, provoking paraneoplastic syndromes. Also, the tumor is able to produce receptors for the tumor necrosis factor. The so-called "cloud", consisting of these receptors, tightly surrounds the focus, protecting it from damage. It is also worth remembering that cytokines have a dual effect. In other words, they can both inhibit and stimulate tumor growth, so the regulatory authorities did not give the go-ahead for the mass use of the drug.

Every patient is faced with the fact that chemotherapy at stages 3 and 4 stops shrinking the tumor and metastases. This is an indication that it is time to move on to more modern methods of cancer therapy. For selection effective method treatment you can ask for

The consultation discusses: - methods of innovative therapy;
- opportunities to participate in experimental therapy;
- how to get a quota for free treatment at an oncology center;
- organizational matters.
After consultation, the patient is assigned the day and time of arrival for treatment, the therapy department, and, if possible, an attending doctor is appointed.