ABSTRACT
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 1.0mg per mouse (12.5-50mg/kg) 3 times a week improved the clinical course. Intraperitoneal injections of 1.0mg 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.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental/drug therapy , Immunologic Factors/therapeutic use , Phenytoin/therapeutic use , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Animals , Anticonvulsants/therapeutic use , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/pathology , Mice , Mice, Inbred C57BL , T-Lymphocytes, Regulatory/pathologyABSTRACT
Forty-five patients with relapsing-remitting multiple sclerosis (MS) were examined to determine intracellular cytokine profiles and the surface phenotype of circulating lymphocytes during active, recovery, and stable stages. Active stage patients were characterized by decreases in CD4(+)IL-4(+) Th2 as well as CD4(+)IFN-gamma(+) Th1 cells, when compared with stable stage patients and 16 healthy controls. CCR4(+) Th2 cells were persistently decreased at every MS stage as compared to the controls. CD4(+)CD29(+) and CD4(+)CXCR3(+) cells were closely correlated with IFN-gamma-producing cells. These findings suggest that simultaneous flow cytometry for these two types of measurements can provide information concerning current immune status in MS.
