STUDY EFFECT OF LEVOFLOXACIN ON SECRETION OF PROINFLAMMATORY CYTOKINES AT THE PULMONARY TUBERCULOSIS (RESEARCH IN VITRO)
Mononuclear leukocytes are key cells that ensure the formation of a specific immune response against Mycobacterium tuberculosis. Cytokines are the main mediators of the immune system, regulating the reactions of nonspecific resistance and specific immunity. Long-term antituberculosis chemotherapy can be accompanied by metabolic disorder and immune system cell dysfunctions associated with the cytotoxic effects of drugs, which can complicate the course of the disease and reduce the efficiency of therapy. To test this hypothesis, it is necessary to study the cytokine-secreting ability of mononuclear leukocytes under conditions of direct action of anti-tuberculosis drugs. In this connection, the aim of this work was to study in vitro the effect of levofloxacin together with the BCG vaccine strain on the production of IL-2, IL-12, IFNγ and TNFα by mononuclear blood leukocytes in patients with infiltrative pulmonary tuberculosis. 39 patients with newly diagnosed infiltrative pulmonary tuberculosis were examined. The first group consisted of 24 patients who isolated mycobacterium tuberculosis sensitive to the main anti-tuberculosis drugs (rifampicin, isoniazid, ethambutol), the second group included 15 patients who isolated mycobacteria resistant to one or more drugs of the main line. The material for the study was peripheral blood. Mononuclear leukocytes were isolated by gradient centrifugation. The incubation medium was supplemented with the BCG vaccine strain (“Microgen”, Russia) at a dose of 50 μg/ml or levofloxacin substance (Sigma-Aldrich, USA) at a dose of 5 μg/ml (comparable to the dose of the drug in its clinical use) in combination with BCG. The incubation medium without the addition of BCG and levofloxacin served as a control. Determination of the level of secretion by mononuclear leukocytes of IL-2, IL-12, IFNγ and TNFα was realized by the method of enzymelinked immunosorbent assay. The combined effect of levofloxacin and the BCG vaccine strain in drug-resistant pulmonary tuberculosis inhibited the production of TNFα, in drug-sensitive tuberculosis inhibited the formation of IL-12 and IFNγ (2 tables, bibliography: 15 refs).