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Am J Physiol Regul Integr Comp Physiol 269: R1469-R1474, 1995;
0363-6119/95 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 269, Issue 6 1469-R1474, Copyright © 1995 by American Physiological Society

ARTICLES

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

A. R. Zampronio, C. A. Silva, F. Q. Cunha, S. H. Ferreira, I. R. Pela and G. E. Souza
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Universidade de Sao Paulo, Ribeirao Preto, Brazil.

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.


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