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-alpha 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.
Fantuzzi
G
G
Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver 80262, USA.
Sacco
S
S
Ghezzi
P
P
Dinarello
C A
CA
D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis / Q000172:deficiency* / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D010529:Peritoneal Cavity; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012016:Reference Values; D012680:Sensitivity and Specificity; D012795:Sialoglycoproteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan / Q000037:antagonists & inhibitors / Q000633:toxicity*
D016207:Cytokines; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan