IL-1␤ is an endogenous pyrogen that is induced during systemic lipopolysaccharide (LPS)-or IL-1-induced fever. We have examined the fever and cytokine responses following i.p. injection of IL-1 agonists, IL-1␣ and IL-1␤, and compared these with response to LPS (i.p.) in wild-type and IL-1␤-deficient mice. The IL-1␤ deficient mice appear to have elevated body temperature but exhibit a normal circadian temperature cycle. Exogenously injected IL-1␤, IL-1␣, or LPS induced hyperresponsive fevers in the IL-1␤-deficient mice. We also observed phenotypic differences between wild-type and IL-1␤-deficient mice in hypothalamic basal mRNA levels for IL-1␣ and IL-6, but not for IL-1␤-converting enzyme or IL-1 receptor type I or type II. The IL-1␣ mRNA levels were down-regulated, whereas the IL-6 mRNA levels were up-regulated in the hypothalamus of IL-1␤-deficient mice as compared with wild-type mice. The IL-1␤-deficient mice also responded to LPS challenge with significantly higher serum corticosterone and with lower serum tumor necrosis factor type ␣ levels than the wild-type mice. The data suggest that, in the redundant cascade of proinf lammatory cytokines, IL-1␤ plays an important but not obligatory role in fever induction by LPS or IL-1␣, as well as in the induction of serum tumor necrosis factor type ␣ and corticosterone responses either by LPS or by IL-1␣ or IL-1␤.

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