CIRCADIAN-RHYTHM OF FEVER INDUCED BY INTERFERON-ALPHA IN MICE

The influence of dosing time on the fever induced by interferon- alpha (IFN- alpha) was investigated in ICR male mice under light-dark cycle . There was a significant circadian rhythm in rectal temperature, as a n index of fever, at 1 hr after IFN- alpha (10 MIU/kg, i.v.) injection . The rhythmic pattern resembled overall the rhythm occuring in the no ndrugged state. IFN- alpha increased rectal temperature during the lig ht phase, but not during the dark phase. The fever induced by IFN- alp ha was blocked by indomethacin (10 mg/kg, i.p.) pretreatment. There wa s no significant difference of plasma IFN- alpha concentrations at 0.1 67, 0.5 and 1 hr after IFN- alpha injection. Therefore the dosing time dependent difference of fever induced by IFN- alpha may be caused via that of PGE2 level elevated by IFN- alpha. The choice of the most app ropriate time of day for drug administration may help to achieve ratio nal chronotherapeutics of IFN- alpha. (C) 1997 Elsevier Science Inc.