Inhibitors of cytochrome p-450 augment fever induced by
interleukin-1 98.
Nakashima, Toshihiro, Yoshiyuki Harada, Seiji Miyata, and Toshikazu
Kiyohara.
Department of Applied Biology, Kyoto Institute of Technology,
Matsugasaki, Sakyo-ku, Kyoto 606, Japan
APStracts 3:0190R, 1996.
Metabolites of cytochrome P-450 are produced in cells when arachidonic
acid cascade is activated. Fever genesis depends largely on the
cyclooxygenase branch of arachidonic acid cascade caused by many
stimuli such as interleukin (IL) -1, IL-6 and interferon-(. To assess
the significance of cytochrome P-450 branch in fever, murine
recombinant IL-1( was bilaterally microinjected (1 ng/SYMBOL 181 \f
"Times New Roman" l) into the medial preoptic area and anterior
hypothalamus in conscious rats treated 60 min previously with or
without cytochrome P-450 inhibitor, econazole (15 mg/kg, i.m.). The
IL-1(-induced rise in colonic temperature was enhanced after plateau
phase of fever (from 240 min after IL-1() in econazole pre-treated
rats (P < 0.001). Another cytochrome P-450 inhibitor,
clotrimazole (15 mg/kg, i.m.) also enhanced IL-1(-induced fever from
160 min after IL-1( injection (P < 0.001). Econazole also
enhanced the fever when it was given 120 min before injection of IL
-1( (P < 0.001). The cytochrome P-450 inhibitor, however, did not
affect the fever when given 10 min after IL-1( (P = 0.95). Econazole
and clotrimazole did not alter normal body temperature (P = 0.65 and
0.73, respectively). The results suggest that the metabolite(s) of
cytochrome P-450 affect the falling phase after the plateau phase of
fever and act as putative endogenous antipyretic(s).
Received 6 September 1995; accepted in final form 8 May 1996.
APS Manuscript Number R548-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 May 96