Nimesulide-induced antipyresis in rats involves both cyclooxygenase-dependent and independent mechanisms.
This study evaluates the antipyretic activity of nimesulide, a cyclooxygenase (COX-2) selective inhibitor in rats. The effects of nimesulide on lipopolysaccharide (LPS)-induced cerebrospinal prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) and on plasma tumor necrosis factor-alpha (TNF-alpha) levels were also evaluated. Male Wistar rats received an i.p. injection of LPS, or i.c.v. injections of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), TNF-alpha, macrophage inflammatory protein-1alpha (MIP-1alpha), arachidonic acid, PGE(2), PGF(2alpha), corticotrophin-releasing factor (CRF) or endothelin-1 (ET-1). Nimesulide or indomethacin administered i.p 30 min prior LPS, IL-1beta, IL-6, TNF-alpha or arachidonic acid reduced the febrile response and PGE(2) or PGF(2alpha) levels in LPS-febrile rats but did not modify PGE(2)-induced fever. Nimesulide, but not indomethacin, reduced the fever induced by MIP-1alpha, PGF(2alpha), CRF or ET-1. Plasma TNF-alpha levels in LPS-treated rats were also reduced by nimesulide. These findings confirm that the antipyretic effect of nimesulide differs from the antipyretic scenario with the non-selective cyclooxygenase blocker indomethacin. Additional mechanisms, including inhibition of increased plasma TNF-alpha, may contribute to its antipyretic activity in rats.
Werner
Maria F P
MF
Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Caixa Postal 19031, Curitiba, PR, 81540-970, Brazil.
Souza
Glória E P
GE
Zampronio
Aleksander R
AR
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015237:Dinoprost / Q000134:cerebrospinal fluid / Q000378:metabolism; D015232:Dinoprostone / Q000134:cerebrospinal fluid / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism; D005334:Fever / Q000097:blood / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000517:prevention & control*; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D003346:Corticotropin-Releasing Hormone; D015237:Dinoprost; D015232:Dinoprostone; C012655:nimesulide; D007213:Indomethacin