Hyperresponsive febrile reactions to interleukin (IL) 1 alpha and IL-1 beta, and altered brain cytokine mRNA and serum cytokine levels, in IL-1 beta-deficient mice

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