PHYSIOLOGICAL AND CYTOKINE RESPONSES IN IL-1-BETA-DEFICIENT MICE AFTER ZYMOSAN-INDUCED INFLAMMATION

Interleukin (IL)-1 beta-deficient (IL-1 beta -/-) mice exhibited decre ased zymosan-induced lethality and reduced production of IL-6 compared with wild-type controls (IL-1 beta +/+). In addition, IL-1 beta -/- m ice had a diminished cellular infiltrate (33%) in the peritoneal cavit y after zymosan. However, anorexia and hypoglycemia were not affected by the lack of IL-1 beta. The induction of corticosterone was only sli ghtly reduced (14%) in IL-1 beta -/- mice. Peritoneal lavage fluid lev els for IL-1 alpha, but not for tumor necrosis factor (TNF)-alpha, wer e also decreased. To evaluate the role of residual IL-1 alpha producti on in IL-1 beta -/- mice, we used IL-1-receptor antagonist (IL-1ra). I n IL-1 beta +/+ mice, IL-1ra inhibited production of IL-6 after zymosa n, 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 demonstra te that IL-1 beta plays a significant, although not exclusive, role in the physiological and cytokine responses to zymosan-mediated inflamma tion.