The mechanisms of anti-inflammatory action of enisamium iodide

Aim. The role of cyclooxygenases (COX-1 and/or COX-2), transcription nuclear factor NF -KB, anti-inflammatory cytokines - TGF1b, IL-4, IL-10 and pro-inflammatory cytokines IL-1, IL-6 were studied to substantiate the expediency of antiviral agent enisamium iodide (Nobazit) using to regulate key inflammatory components in acute respiratory infections, IL-8, TNF-alpha in the realization of the pharmacological activity of this drug. Materials and methods. Gene expression was determined by real-time RT-PCR, the concentration of interleukins was determined by ELISA, and the viability of peripheral blood mononuclear cells (PBMC) was assessed by the MTT spectrophotometric method. The chemiluminescence method was used to assess PBMC oxidant activity. Results. Enisamium iodide (10 mu M) reduced mRNA levels of COX-1, COX-2, NF -KB, TGF1b, IL-1, IL-6 in stimulated PBMC of healthy donors by an average of 48% (p <= 0.05). At 5 times higher concentration, 50 mu M, enisamium iodide suppressed the expression of these genes by an average of 43% (p <= 0.05). At a concentration of 100 mu M, enisamium iodide reduced the expression of COX-2, TGF1b, IL-1, IL-6 by an average of 47% (p <= 0.05). At a concentration of 10 mu M, enisamium iodide stimulated the secretion of IL-10 by mononuclear cells by 1.2 times, p <= 0.05. The tested drug at a concentration of 50 mu M did not affected on the concentration of IL-1, IL-4, IL-8 and TNF-alpha, but significantly stimulated the production of IL-10 by 1.5 times, p <= 0.05. The chemiluminescence method revealed that enisamium iodide in the entire concentration range (10-100 mu M) does not reduce the viability of macrophages, but inhibits their oxidative activity (maximum value of CL intensity) by an average of 55% (p <= 0.05). Conclusion. The anti-inflammatory effect of enisamium iodide at a concentration of 10 mu M may be associated with inhibition of the expression of COX-1, 2, NF -KB, IL-1, IL-6, TGF1b and an increase in the expression and production of IL-10. An additional contribution to the anti-inflammatory activity of enisamium iodide is made by its antioxidant and antiradical activity. The absence of the effect of enisamium iodide (10-100 mu M) on the viability of PBMC indicates its safety for the cells of the immune system and the expediency of using it to suppress inflammatory reactions in acute respiratory infections, restore the quality of life of patients and the possibility of using Nobazit as an effective agent for treatment of these infections of various etiologies.