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 haemoc yanin (KLH) IgE antibody response after KLH-immunization was enhanced in ph enytoin-treated mice. Proliferative responses of spleen cells induced with KLH, concanavalin A (ConA), lipopolysaccharide and anti-CD3 antibody were r educed in phenytoin-treated mice. Accessory function of spleen adherent cel ls on ConA-induced T cell proliferative response was reduced in phenytoin-t reated mice. KLH-induced IL-4 production of spleen cells was enhanced, whil e 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 f rom phenytoin-treated mice was reduced. Natural killer cell activity was re duced in phenytoin-treated mice. These results suggest that phenytoin treat ment preferentially induces a Th2 type response. We also observed that plas ma ACTH and corticosterone levels were increased in phenytoin-treated mice, and speculated that phenytoin might act directly and indirectly, through H PA axis activation, on the immune system to modulate Th1/Th2 balance.