Stepanova T. Efficacy and some mechanisms of Amixin effect at experimental allergic encephalomyelitis

Thesis covers the study of Amixin efficacy at experimental allergic encephalomyelitis (EAE) and mechanisms of its immunomodulatory and anti-inflammatory effect. It was shown that Amixin slowed down the disease course in mice. No fatal cases were registered after drug administration, and 15,6 % of mice have not shown any clinical implications. The number of mice with 3+ and 4+ severity levels was 1,7-1,75 times lower (р?0,01) compared to EAE control. Immunomodulating effects of Amixin were shown in inhibition of IFN-? and TNF-? synthesis, increase of CD8 lymphocyte number and decrease of CD4/CD8 cell ratio. Amixin has shifted T-helper balance towards Th2 cells and slowed cytotoxic reactions down. It was shown that anti-inflammatory activity of Amixin was realized trough the suppression of inflammatory cytokines synthesis, decrease of proteolytic enzymes (catepsin D and elastase) activity and cortisol level recovery in blood serum. Amixin inhibited lipid peroxidation rate as well as active oxygen and NO formation. The drug increased general antioxidant activity, one of the mechanisms of which was hemoxigenase-1 induction in macrophage cells including those in neuroinflammation focus. It was demonstrated that Amixin in vitro directly inhibited pro-inflammatory cytokines synthesis and induced hemoxigenase.