ROLE OF IL-4, IL-6, IL-8, IL-10 CYTOKINES IN THE IMMUNOPATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease (COPD) is socially significant disease. COPD is based on chronic inflammatory process of respiratory tract, which determines steady progression of the bronchial obstruction. Studies of the role of cytokines in immune pathogenesis of COPD are of crucial importance. The biological mediators determine local, systemic inflammation, and pathophysiological effects of extra-systemic pathological manifestations. In this work, we studied spontaneous and induced production of IL-4, IL-6, IL-8, IL-10 cytokines by blood leukocytes from the patients with moderate and severe chronic obstructive pulmonary disease, beyond the exacerbation phase. It is shown that the evident role in formation of the inflammatory process in COPD belongs to the IL-6, IL-8. We have found a significant increase in both spontaneous and induced production of IL-6 and IL-8 (p < 0.05) in the patients. Induced production of cytokines strongly suggests the reserve capabilities of immunocompetent cells in response to the pathogenic factor. Neutrophilic type of inflammation, manifesting as activation of granulocytes, mostly, neutrophils, in response to toxic agents (in particular, smoking) and bacterial pathogens, is primarily associated with IL-6 and IL-8. These results reflect the type and intensity of respiratory tract inflammation in patients with chronic obstructive pulmonary disease and its persistent course.

High levels of the studied cytokines confirm their role in bronchial remodeling and contribute to irreversibility of bronchial obstruction in this disorder. The relationship between spontaneous and induced production of the studied cytokines and the clinical indices of the disease course has been shown. Statistically significant increase between frequency of COPD recurrences (more than 2 times pro year, p < 0.05), and low FEV₁ values (p < 0.05) were observed in patients with high values of spontaneous and induced production of IL-6 and IL-8. It may be associated with persistent course of neutrophilic inflammation of respiratory tract and progressive bronchial obstruction. IL-6 and IL-8 significantly contribute to pathogenetic mechanisms, determining the clinical course of COPD and may serve as markers of severity in this disorder. Certainly, the immune mechanisms of pathological inflammation in COPD are complex and multifaceted. Studies of clinical significance of induced cytokine production will help the physician when determining type and duration of treatment. Personalized approach to the therapy of patients with COPD depends on the phenotype of pathology, pattern, severity and intensity of inflammation.

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