IN VITRO STUDY OF THE DOSE-DEPENDENT EFFECT OF JANUS KINASE INHIBITORS

Abstract

Background. One of the most promising means of targeting the mechanisms of autoimmune processes and hyperimmune reactions associated with cytokine imbalance are Janus kinase inhibitors. However, these chemicals in the used doses have a number of undesirable side effects. The effect of small and ultra-low doses in relation to this group of substances has not been studied. Purpose. To study the effect of low and ultra-low concentrations of Janus kinase inhibitors on the synthesis of cytokines by human mononuclear cells in vitro. Materials and methods. The concentrations of tumor necrosis factor alpha (TNFα), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon alpha (IFNα), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8) and interleukin 10 (IL-10) after stimulation with phytohemagglutinin were determined in the culture of mononuclear cells of healthy donors. Also the effect on the production of these cytokines of ruxolitinib and baricitinib in various doses, including ultra-low ones, was determined. Results. It was found that baricitinib, as well as ruxolitinib, at normal concentrations significantly decreased, and at ultra-low concentrations they significantly increased the level of synthesis of all cytokines studied in this experiment. Conclusion. The stimulating, but not suppressive effect of ultra-low concentrations of Janus kinase inhibitors has been demonstrated using the example of ruxolitinib and baricitinib. In relation to inhibitors of Janus kinase functions, this phenomenon has been discovered for the first time, which opens up ways to search for new means of regulating immunity, in particular, the production of cytokines.