Indomethacin blocks the febrile response induced by interleukin-8 in rabbits.
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.
Zampronio
A R
AR
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, Ribeirão Preto, Brazil.
Silva
C A
CA
Cunha
F Q
FQ
Ferreira
S H
SH
Pelá
I R
IR
Souza
G E
GE
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology; D016209:Interleukin-8 / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D016209:Interleukin-8; D011994:Recombinant Proteins; D007213:Indomethacin