Indomethacin blocks the febrile response induced by interleukin-8 in rabbits

• Published in: The American journal of physiology Vol. 269; no. 6 Pt 2; pp. R1469 - R1474
• Main Authors: Zampronio, A R, Silva, C A, Cunha, F Q, Ferreira, S H, Pelá, I R, Souza, G E
• Format: Journal Article
• Language: English
• Published: United States 01-12-1995
• Subjects: Animals; Cyclooxygenase Inhibitors - pharmacology; Fever - chemically induced; Fever - prevention & control; Humans; Indomethacin - pharmacology; Injections, Intravenous; Injections, Intraventricular; Interleukin-1 - administration & dosage; Interleukin-1 - pharmacology; Interleukin-8 - administration & dosage; Interleukin-8 - pharmacology; Male; Rabbits; Rats; Recombinant Proteins
• ISSN: 0002-9513
• DOI: 10.1152/ajpregu.1995.269.6.r1469

Interleukin (IL)-8 induces fever in rats by a mechanism independent of the release of cyclooxygenase products. The purpose of this study was to investigate whether a similar mechanism is responsible for the pyrogenic effect of IL-8 in rabbits. Intravenous (0.31-5.0 ng/kg) or intracerebroventricular (15.6-250 pg) injections of IL-8 induced a dose-dependent increase in body temperature. The correlations between the doses of recombinant human IL-8 and the fever index were 0.98 and 0.99 for the intravenous and intracerebroventricular injections, respectively. The pyrogenic activity of IL-8 was not due to contamination with lipopolysaccharide (LPS), inasmuch as the Limulus amoebocyte lysate test showed < 10 pg endotoxin/micrograms IL-8, and boiled IL-8 lost its pyrogenic activity. Indomethacin (2 and 5 mg/kg i.p.) abolished the febrile response induced by the intravenous injection of LPS (5.0 ng/kg), IL-1 beta (5 ng/kg), and IL-8 (5 ng/kg). Indomethacin also abolished the fever induced by the intracerebroventricular injection of IL-8 (62.5 pg) but only partially reduced the response induced by the injection of IL-1 beta (25 pg icv). These results show that, different from rats, indomethacin blocks the febrile response induced by the central or peripheral administration of IL-8 in rabbits.