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Makhmudova Zulfiya Primkulova, senior researcher, Republican Specialized Scientific Practical Medical Center Phthisiology and Pulmonology
E-mail: evovision@bk.ru
THE ROLE OF PROINFLAMMATORY CYTOKINES IN THE PATHOGENESIS OF TUBERCULOSIS
Abstract: Foci of inflammation, formed during TB, include a whole cascade of metabolic reactions on the part of the body aimed at limiting the focus of inflammation and restoring local homeostasis. As a result of the inflammatory reaction around the focus of inflammation, synthesis of acute phase proteins predominates, the level of which is regulated by various inducers. Such inducers include proinflammatory cytokines, primarily IL-1^ and tumor necrosis factor, which are synthesized by various cells surrounding the ischemic focus - fibroblasts, vascular endothelium, activated macrophages and T-lymphocytes. At a high concentration, IL-1^ becomes a mediator of tissue damage, triggers a mechanism of increased production of TNF-a, which in turn has a damaging effect on body tissues.
Keywords: Cytokines, pathogenesis, primarily, tuberculosis.
In the pathogenesis of TB, cytokines play a significant Purpose of the study. Study of pathogenetic mecha-
role. Cytokines regulate the development of local protec- nisms of development of tuberculous spondylitis in pa-
tive reactions of the body in tissues involving various types of blood cells, endothelium, connective tissue and epithelium [1, 3]. TNF-a is a pro-inflammatory cytokine produced by various cells, including activated T cells, keratinocytes and Langerhans cells. TNF-a has multiple effects in the development of an immune response, triggering activation and a set of inflammatory cells, increasing the production of pro-inflammatory cytokines IL-1, IL-6 and IL-8, and activating nuclear transcription factors such as NF-KB to maintain an immune response. At TB, elevated levels of TNF-a and TNF-a receptor expression are noted. TNF-a induces the maturation of Langerhans cells, also stimulates the migration of mature Langerhans cells from the skin to the lymph nodes where the interaction between antigen-presenting cells and T cells occurs. TNF-a increases the proliferation of keratinocytes in vitro. It is suggested that TNF-a blocks apoptosis of keratinocytes and contributes to a longer lifetime of keratinocytes in the skin of patients with TB. TNF-a affects the vascularization of the skin and promotes increased expression of endothelial adhesion molecules involved in the migration of T cells. In addition, TNF-a increases the production of vascular endothelial growth factor (VEGF), which leads to vascular proliferation [5].
tients with lung involvement.
Material and methods. The study was based on a clinical laboratory examination of 100 patients with various forms of pulmonary tuberculosis, of which 45 patients with pulmonary tuberculosis combined with tuberculosis spondylitis who were hospitalized in the pulmonary tuberculosis and osteoarticular tuberculosis departments of the Republican Specialized Scientific and Practical Medical Center of Phthisiology and Pulmonology of the Ministry of Health of the Republic of Uzbekistan, of comparable age in the period from 2014 to 2016.
The level of proinflammatory cytokines was determined by the method of enzyme immunoassay
Results and its discussion. The main role in the pathogenesis of spondylitis in patients with TB is given to T cells, especially CDS + cells, which promote increased production of cytokines, including IL-1, IL-2, IL-10, TNF-a, in synovial fluids in patients with AB. These cytokines induce the proliferation and activation of synovial and epidermal fibroblasts, leading to the formation of fibrosis in patients with long-standing arthritis. TNF-a is associated with bone and cartilage destruction in arthritis. The pro-inflammatory cytokines IL-1j8 and TNF-a also play an important role in
Section 7. Medicine
bone metabolism by increasing the osteoclastogen-esis through up-regulation of oste-oprotegerin ligand (OPGL), a new molecule that is a receptor of TNF-a expressed by activated T cells. Erosive changes are as-
Interleukin-increased to 157.8 pg/ml, which is an increase in the level of 4.4 times with the surface form and up to 199.1 pg/ml - in 5.6 times in the patients of the main group compared with the control group. The tumor necrosis factor (TNF- a) with the surface form of AB increased by 1.28 times, and in patients of the main group - by 1.94 times. Obviously, there is a clear tendency to increase the value of cytokine indices during the process chronicization.
Inflammation develops in response to damage and penetration into the tissue of pathogens with the participation of pro-inflammatory cytokines. These cytokines are synthesized in the inflammatory focus by macrophage cells. They cause activation of the endothelium, leading to increased permeability, increased expression of adhesion molecules and increased procoagulant activity. There is an outburst of low-molecular inflammatory mediators, such as histamine, prosta-glandins. Simultaneously, proinflammatory cytokines activate the metabolism of connective tissue, stimulate the proliferation of fibroblasts and epithelial cells, which is important for healing the damage and restoring tissue integrity.
Foci of inflammation, formed during TB, include a whole cascade of metabolic reactions on the part of the body aimed at limiting the focus of inflammation and restoring local homeostasis. As a result of the inflammatory reaction around the focus of inflammation, synthesis of acute phase proteins predominates, the level of which is regulated by various inducers. Such inducers include proinflammatory cytokines, primarily IL-1j8 and tumor necrosis factor, which are synthesized by various cells surrounding the ischemic focus - fibroblasts, vascular endothelium, activated macrophages and T-lymphocytes. At a high concentration, IL-1 becomes a mediator of
sociated with elevated levels of osteoclast precursors in peripheral blood.
Thus, TNF-a and IL-1^ play a key role among inflammatory mediators in the pathogenesis of TB (Table 1).
tissue damage, triggers a mechanism of increased production of TNF-a, which in turn has a damaging effect on body tissues.
In clinical practice, immunological studies in patients with tuberculosis are used for the purpose of not only diagnosing and elucidating the state of the patient's immune system, but may also be important for determining the prognosis of the course of the disease, detecting a possible relapse. Of particular importance is the analysis of nonspecific and specific indicators, the duration of significant disturbances, and their comparison with: clinical and radiological symptomatology of the process. Long-term preservation of T-cell deficiency, high levels of auto- and anti-tuberculosis antibodies, absent or decreased response of lymphocytes to tuberculin is characteristic of the progressive course of tuberculosis. The presence of these signs at early stages of observation should be the basis for the inclusion of pathogenetic agents in the comprehensive therapy of tuberculosis.
Immunological studies can be used to determine the effectiveness of treatment and the completeness of recovery of patients. Comparing the nature of disorders in the immune system to treatment, during and after therapy, it is possible to identify a certain dynamics of changes. In most cases, with effective therapy, there is an improvement in immunological parameters, and in some patients - their normalization. However, clinical recovery usually outstrips the normalization of the immune status.
Conclusion. At a high concentration, IL-1^ becomes a mediator of tissue damage, triggers a mechanism of increased production of TNF- a, which in turn has a damaging effect on body tissues.
Table 1.- Indicators of IL-1ß and TNF- a in tuberculosis
Indicators Control group (n = 30) Comparison group (n = 55) The main group (n = 45)
IL-1ß nr/MA 35.3 ± 0.5 157. ± 80.7*** 1991 ± 1 4***AAA
TNF- a, nr/MA 3.73 ± 0.91 4.77 ± 0.73 7.26 ± 0.89**A
Note: * - the differences with respect to the control group are significant (** - P < 0.01, *** - P <0.001), the D-differences with respect to the data of group 1 are significant (A - P < 0.05, AAA - P < 0.001)
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