Interleukin-8 induces fever by a prostaglandin-independent mechanism.
We have studied the mechanism by which interleukin-8 (IL-8) induces fever in rats. Intracerebroventricular injections of IL-8 (5.5-50 ng) evoked dose-dependent increases in body temperature, which reached a plateau 5 h after injection, i.e., later than intracerebroventricular interleukin-1 beta (IL-1 beta; 2 h). The pyrogenic activity of IL-8 was not due to contamination with lipopolysaccharide (LPS) because preincubation of IL-8 with a specific antibody or boiling the IL-8 for 30 min abolished its activity but not that of LPS; also, IL-8 but not LPS induced fever in LPS-tolerant rats. Indomethacin significantly reduced the pyrogenic effects of intracerebroventricular injections of LPS and IL-1 beta but not responses to IL-8, suggesting that pyrogenic responses to IL-8 were mediated independently of prostaglandins. In contrast, dexamethasone markedly attenuated pyrogenic responses to IL-8 and IL-1 beta. These data suggest that inhibition of IL-8 by glucocorticoids contributes to the antipyretic effects of these drugs in fevers resistant to cyclooxygenase inhibitors.
Zampronio
A R
AR
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, Ribeirão Preto, Brazil.
Souza
G E
GE
Silva
C A
CA
Cunha
F Q
FQ
Ferreira
S H
SH
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007276:Injections, Intraventricular; D016209:Interleukin-8 / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D016209:Interleukin-8; D008070:Lipopolysaccharides; D011453:Prostaglandins; D011994:Recombinant Proteins; D003907:Dexamethasone; D007213:Indomethacin