Indomethacin blocks the febrile response induced by interleukin-8
in rabbits.
Zampronio, Aleksander R., Carlos A. A. Silva, Fernando Q. Cunha,
S[acute]ergio H. Ferreira, Irene R. Pel[acute]a, & Gl[acute]oria
E. P. Souza.
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences,
Department of Pharmacology, Faculty of Medicine, Ribeir_o Preto, USP
Campus-l4040-903 Ribeir_o Preto, S.P., Brazil
APStracts 2:0197R, 1995.
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 (iv, 0.31 - 5.0
ng/kg) or intracerebroventricular (icv, 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 iv and icv injections,
respectively. The pyrogenic activity of IL-8 was not due to
contamination with lipopolysaccharide (LPS) since the Limulus
amoebocyte lysate test (LAL) showed less than 10 pg endotoxin/[mu]g
IL-8 and boiled IL-8 lost its pyrogenic activity. Indomethacin (2 and
5 mg/kg, ip) abolished the febrile response induced by the iv
injection of LPS (5.0 ng/kg), interleukin-1[beta] (IL-1[beta], 5
ng/kg) and IL-8 (5ng/kg). Indomethacin also abolished the fever
induced by the icv injection of IL-8 (62.5 pg) but only partially
reduced the response induced by the icv injection of IL-1[beta] (25
pg). These results show that, different from rats, indomethacin
blocks the febrile response induced by the central or peripheral
administration of IL-8 in rabbits.
Received 4 October 1994; accepted in final form 6 July 1995.
APS Manuscript Number R568-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.