Phenytoin at optimum doses ameliorates experimental autoimmune encephalomyelitis via modulation of immunoregulatory cells

We investigated the optimum doses of phenytoin for treatment of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Oral and intraperitoneal administrations of 0.25 to 1.0 mg per mouse (12.5-50 mg/kg) 3 times a week improved the clinical course. Intraperitoneal injections of 1.0 mg phenytoin were the most effective, as a significant reduction in EAE severity was seen after only 2 administrations with that protocol. Treatment efficacy was associated with amelioration of cellular infiltrates in the CNS, and an increase in CD4+Foxp3+ and CD4+CD25+CD127− regulatory T cells as well as CD8+ suppressor/cytotoxic T cells in blood.