Characterization of the febrile response induced by fibroblast-stimulating lipopeptide-1 in guinea pigs.
Recently, it has been shown that the Toll-like receptors-2 and -6 agonist fibroblast-stimulating lipopeptide-1 (FSL-1) have the capacity to induce fever and sickness behavior in rats. Since the mechanisms of the fever-inducing effects of FSL-1 are still unknown, we tested the pyrogenic properties of FSL-1 in guinea pigs and assessed a role for TNF-alpha and prostaglandins in the manifestation of the febrile response to this substance. Intra-arterial and intraperitoneal injections of FSL-1 caused dose-dependent fevers that coincided with elevated plasma levels of TNF and IL-6, the intraperitoneal route of administration being more effective than the intra-arterial route. Intra-arterial or intraperitoneal injection of a soluble form of the TNF type 1 receptor, referred to as TNF binding protein (TNFbp), together with FSL-1, completely neutralized FSL-1-induced circulating TNF and reduced fever and circulating IL-6. Intra-arterial or intraperitoneal injection of the nonselective cyclooxygenase (COX)-inhibitor diclofenac depressed fever and FSL-1-induced elevations of circulating PGE2. Circulating TNF and IL-6, however, remained unimpaired by treatment with diclofenac. In conclusion, FSL-1-induced fever in guinea pigs depends, in shape and duration, on the route of administration and is, to a high degree, mediated by pyrogenic cytokines and COX products.
Greis
Andrea
A
Institut für Veterinär-Physiologie, Justus-Liebig-Universität Giessen, Frankfurter Strasse 100, D-35392 Giessen, Germany.
Murgott
Jolanta
J
Rafalzik
Sandra
S
Gerstberger
Rüdiger
R
Hübschle
Thomas
T
Roth
Joachim
J
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004008:Diclofenac / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D006168:Guinea Pigs; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D047990:TNF Receptor-Associated Factor 1 / Q000737:chemistry / Q000494:pharmacology; D013686:Telemetry
D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D004075:Diglycerides; C460864:FSL-1 lipoprotein, synthetic; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009842:Oligopeptides; D047990:TNF Receptor-Associated Factor 1; D004008:Diclofenac; D011092:Polyethylene Glycols; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone