Reduction of free radicals in multiple sclerosis: effect of glatiramer acetate (Copaxone(R))

Free radicals have been found in high concentrations within inflammatory multiple sclerosis (MS) lesions. The superoxide anion (O2 –) reacts rapidly with nitric oxide (NO), producing peroxynitrite (ONOO–). Glatiramer acetate (GA) is a specific MS immunomodulator that induces the synthesis of Th2 cytokines, and reduces the frequency of relapses and the formation of active brain lesions. Proinflammatory cytokines could play a role in free radicals production in the peripheral immune system as well as in the central nervous system (CNS). The effect of GA on iNOS, superoxide radicals (O2 –) and 3-nitrotyrosine production by peripheral blood adherent mononuclear cells (PBAMs) was assessed. Our findings demonstrate that in vitro GA reduced spontaneous and LPS-induced iNOS, 3-nitrotyrosine, NO and O2 – production, and that similar inhibition can be demonstrated ex vivo in mononuclear cells obtained from GA-treated patients. The inhibition of the production of free radicals in PBAMs may represent a new therapeutic mechanism against inflammation during MS