title: Nimesulide and diclofenac inhibit lipopolysaccharide-induced hypothermia and tumour necrosis factor-alpha elevation in rats.
abstract: The effects of nimesulide and diclofenac on lipopolysaccharide (LPS)-induced rectal temperature changes and serum tumour necrosis factor (TNF)-alpha elevation were investigated in rats. LPS (Escherichia coli O111:B4; 50 microg/kg, intraperitoneally) produces a dual body temperature response, in which initial hypothermia precedes fever. Serum TNF-alpha levels rise during the initial phase of the induced hypothermia. Nimesulide, a preferential inhibitor of cyclooxygenase-2 (0.05, 0.5 or 1 mg/kg, subcutaneously) completely abolished the hypothermia, resulting in an acceleration of the fever phase. However, the peak and plateau phases of fever were not changed by nimesulide treatment. Nimesulide (0.5 mg/kg) partially prevented serum TNF-alpha elevation. The non-selective cyclooxygenase inhibitor diclofenac inhibited hypothermia at all doses tested (0.03, 0.3 or 3 mg/kg, subcutaneously) although fever was completely abolished at the 3 mg/kg dose only. Diclofenac also partially abolished the elevation in serum TNF-alpha levels, but at the highest dose only (3 mg/kg). These data suggest that nimesulide and diclofenac can preferentially inhibit LPS-induced hypothermia at doses that do not abolish fever in rats. Both these drugs also reduced elevated TNF-alpha levels, a fact which may, at least partly, explain the antihypothermic effect of nimesulide.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Ankara University, Sihhiye, Ankara, Turkey.
authors.forename: Muberra Devrim
authors.initials: MD
authors.lastname: Dogan
authors.forename: Haluk
authors.initials: H
authors.lastname: Ataoglu
authors.forename: Eyup S
authors.initials: ES
authors.lastname: Akarsu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D004008:Diclofenac; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide