Physiological and cytokine responses in IL-1 beta-deficient mice after zymosan-induced inflammation

Interleukin (IL)-1 beta-deficient (IL-1 beta -/-) mice exhibited decreased zymosan-induced lethality and reduced production of IL-6 compared with wild-type controls (IL-1 beta +/+). In addition, IL-1 beta -/- mice had a diminished cellular infiltrate (33%) in the peritoneal cavity after zymosan. However, anorexia and hypoglycemia were not affected by the lack of IL-1 beta. The induction of corticosterone was only slightly reduced (14%) in IL-1 beta -/- mice. Peritoneal lavage fluid levels for IL-1 alpha, but not for tumor necrosis factor (TNF)-alpha, were also decreased. To evaluate the role of residual IL-1 alpha production in IL-1 beta -/- mice, we used IL-1-receptor antagonist (IL-1ra). In IL-1 beta +/+ mice, IL-1ra inhibited production of IL-6 after zymosan, without affecting TNF-cu synthesis. There was no further inhibitory effect of IL-1ra on IL-6 production in IL-1 beta -/- mice, suggesting no role for IL-1 alpha in zymosan-induced IL-6. Our results demonstrate that IL-1 beta plays a significant, although not exclusive, role in the physiological and cytokine responses to zymosan-mediated inflammation.