Interleukin-8 induces fever by a prostaglandinindependent mechanism

(Regulatory Integrative Comp. Physiol. 35): R1670-R1674, 1994.-We have studied the mechanism by which interleu-kin-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 interleu-kin-lp (IL-lp; 2 h). The pyrogenic activity of IL-8 was not due to contamination with lipopolysaccharide (LPS) because prein-cubation 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 intracerebroven-tricular injections of LPS and IL-lb but not responses to IL-8, suggesting that pyrogenic responses to IL-8 were mediated independently of prostaglandins. In contrast, dexamethason