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 1.0mg 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.
Department of Neurology, Kanazawa Medical University, Uchinada, Ishikawa Prefecture 920-0293, Japan.
Naomi
N
Hashiba
Shigemi
S
Nagayama
Shin-Ich
SI
Araya
Hiroyuki
H
Inada
Yoshifumi
Y
Sonobe
Akio
A
Suzumura
Makoto
M
Matsui
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007155:Immunologic Factors / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D010672:Phenytoin / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology
D000927:Anticonvulsants; D007155:Immunologic Factors; D010672:Phenytoin