Effect of interleukin 1β-induced fever on hepatic drug metabolism in rat

Abstract

1. A fever-induced modelinrat was created by repeated injection of interleukin 1β(IL-1β) in the cerebroventricle and the influence of fever on hepatic drug metabolism was investigated. Fever apparently decreased the content of cytochrome P450 (CYP) and the activities of NADPH-ferrihaemoprotein reductase (ƒ_p2), aminopyrine N-demethylase, aniline hydroxylase, FAD-monooxygenase, p-nitrophenol UDP-glucuronosyl-transferase and glutathione S-transferase. Immunoblot analysis of the CYP isozymes indicated that CYP2C11 and CYP3A were extensively decreased in the IL-1β-induced fevered rat. 2. Repeated administration (5 days) of mefenamic acid in the fevered rat could not restore the activities of ƒ_p2, aminopyrine N-demethylase and aniline hydroxylase to control plevels, although their hyperthermic state had been improved. 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 some conjugations) and that the fever-induced impairments are partially retained, even if the hyperthermia has been offset by the administration of antipyretics.