Features of the effect of antioxidant status on the production of cytokines and pro-inflammatory molecules under stimulation of human whole blood cells with mitogen and lipopolysaccharide

Relevance. Antioxidants play an important role in the prevention of various pathological conditions, including radiation damage, infections, immune response, etc. Antioxidant deficiency against the background of increased peroxidation processes is associated with the progression of various pathological processes, including infectious inflammation. The relationship between the activity of the antioxidant system and the state of lipid peroxidation is interrelated with the phosphorylation of individual intracellular enzymes involved in the functioning of receptor-associated signaling pathways. It has been shown that antioxidants have an immunomodulatory effect in infectious processes, contributing to a change cytokine production, phagocytosis activity, antibody production, etc. The aim of the study was to characterize the effect of antioxidants on the production of cytokines stimulated by mitogen and lipopolysaccharide and the content of terminal MAPK/SAPK protein kinases in mononuclear leukocytes. Material and Methods. The material for the study was venous blood taken in the morning from the cubital vein from practically healthy individuals from among blood donors of both sexes aged 20-25 years. In whole blood mononuclear cell (MNC) lysates, the content of stress-activated protein kinase JNK 1 and 2 isoforms (JNK1/2), mitogen-activated protein kinase p38, and the level of the p65 subunit of the nuclear transcription factor NF-kB were assessed by ELISA. In the supernatants, the level of interleukins (IL) was studied: IL-1ß, -2, -4, -6, -8, -10, -12, -13, -17A, -19, -21, -22, -23, - 28, TNFa, IFNy, RAIL-1, TRGF, GM-CSF, lipopolysaccharidebinding protein, cAMP, concentration of antioxidants and peroxides. Results. The analysis showed that a high level of antioxidant activity in the blood against the background of mitogenic stimulation and exposure to lipopolysaccharide cells is associated with an increase in the production of IL-10, IL-12, GM-CGF, IL-4, COX-2, cAMP, SOD, as well as a decrease in levels of IL-1, IL-17A, lipopolysaccharide-binding protein, a decrease in the content of JNK and p38 protein kinases in MNCs. Conclusions. A high level of antioxidants contributes to a partial weakening of the pro-inflammatory activity of whole blood cells subjected to mitogenic stimulation and activation by lipopolysaccharide. The immunoregulatory effects of antioxidants are determined by changes in the MNC activity of terminal protein kinases of the MAPK/SAPK signaling pathway, in particular, JNK and p38 is possible due to cAMP activation of the PKA/CREB signaling pathway.