Phenytoin promotes Th2 type immune response in mice.
The effects of chronic administration of phenytoin, a common anticonvulsive drug, on immune responses were studied in mice. Anti-keyhole limpet haemocyanin (KLH) IgE antibody response after KLH-immunization was enhanced in phenytoin-treated mice. Proliferative responses of spleen cells induced with KLH, concanavalin A (ConA), lipopolysaccharide and anti-CD3 antibody were reduced in phenytoin-treated mice. Accessory function of spleen adherent cells on ConA-induced T cell proliferative response was reduced in phenytoin-treated mice. KLH-induced IL-4 production of spleen cells was enhanced, while IFN-gamma production was reduced in phenytoin-treated mice. In addition, production of IL-1 alpha, but not IL-6 and IL-12 by spleen adherent cells from phenytoin-treated mice was reduced. Natural killer cell activity was reduced in phenytoin-treated mice. These results suggest that phenytoin treatment preferentially induces a Th2 type response. We also observed that plasma ACTH and corticosterone levels were increased in phenytoin-treated mice, and speculated that phenytoin might act directly and indirectly, through HPA axis activation, on the immune system to modulate Th1/Th2 balance.
Okada
K
K
Department of Immunology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Sugiura
T
T
Kuroda
E
E
Tsuji
S
S
Yamashita
U
U
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000917:Antibody Formation; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D006433:Hemocyanins / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010672:Phenytoin / Q000008:administration & dosage / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D000927:Anticonvulsants; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010672:Phenytoin; D000324:Adrenocorticotropic Hormone; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D003345:Corticosterone