Inhibition of nitric oxide synthase results in a suppression of interleukin-1beta-induced fever in rats.
Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) induce nitric oxide synthase. The purpose of this study was to investigate the role of endogenous nitric oxide in IL-1beta-induced fever in rats. At a dose of 2.5 microg per animal intraperitoneal (i.p.) injections of rat recombinant IL-1beta evoked a febrile response with a duration of 8 hours. Simultaneous i.p. injection of 50 mg/kg N-nitro-L-arginine methyl ester hydrochloride (L-NAME) resulted in a complete suppression of IL-1beta-induced fever in rats. I.p. injection of 50 mg/kg L-NAME alone had no apparent influence on body core temperature. Endogenous formation of IL-6 in response to IL-1beta was not suppressed but rather enhanced by treatment with L-NAME during the early stage of IL-1beta-induced fever. This result indicates that activation of nitric oxide synthase and thereby endogenous NO-formation is essential for the generation of an IL-1beta-induced febrile response in rats and that the suppression of IL-1beta-induced fever by treatment with L-NAME seems not to be caused by an inhibition of IL-6 production.
Roth
J
J
Institut für Normale und Pathologische Physiologie, Marburg, Germany.
Störr
B
B
Voigt
K
K
Zeisberger
E
E
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007375:Interleukin-1 / Q000633:toxicity*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000633:toxicity
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester