EFFECT OF INTERLEUKIN 1-BETA-INDUCED FEVER ON HEPATIC DRUG-METABOLISMIN RAT

1. A fever-induced model in rat was created by repeated injection of i nterleukin 1 beta (IL-1 beta) in the cerebroventricle and the influenc e of fever on hepatic drug metabolism was investigated. Fever apparent ly decreased the content of cytochrome P450 (CYP) and the activities o f NADPH-ferrihaemoprotein reductase (f(p2)), aminopyrine N-demethylase , aniline hydroxylase, FAD-monooxygenase, p-nitrophenol UDP-glucuronos yl-transferase and glutathione S-transferase. Immunoblot analysis of t he CYP isozymes indicated that CYP2C1 1 and CYP3A were extensively dec reased in the IL-1 beta-induced fevered rat. 2. Repeated administratio n (5 days) of mefenamic acid in the fevered rat could not restore the activities off f(p2), aminopyrine N-demethylase and aniline hydroxylas e to control levels, although their hyperthermic state had been improv ed. The CYP content in the mefenamic acid-treated fevered rat was also lower than that in the control. 3. These findings suggest that fever impairs the hepatic drug-metabolizing capacity (both oxidation and som e conjugations) and that the fever-induced impairments are partially r etained, even if the hyperthermia has been offset by the administratio n of antipyretics.