Effect of endotoxin in IL-1 beta-deficient mice.
IL-1 plays an important role in the pathophysiologic responses to infection and inflammation, in part by mediating its own production and that of other proinflammatory cytokines. However, the relative contribution of IL-1 alpha and IL-1 beta to the inflammatory response has not been well clarified. Using IL-1 beta-deficient (IL-1 beta -/-) mice, we investigated the specific role of IL-1 beta in the in vivo and in vitro response to LPS. No differences between IL-1 beta +/+ and IL-1 beta -/- mice were observed in circulating levels for IL-1 alpha, IL-6, or TNF-alpha after the systemic administration of either a low (5 micrograms/kg) or high (5 mg/kg) dose of LPS. IL-1 beta -/- mice also had a normal response to LPS in terms of activation of the hypothalamus-pituitary-adrenal axis, hypoglycemia, serum amyloid A production, and anorexia. IL-1 beta -/- mice were normally sensitive to the lethal effect of LPS and were protected against LPS toxicity when pretreated with low-dose LPS. However, in vitro, peritoneal macrophages from IL-1 beta -/- mice stimulated with LPS produced significantly less IL-1 alpha than macrophages from IL-1 beta +/+ mice (p < 0.05). No differences in IL-6 or TNF-alpha synthesis were observed between macrophages from IL-1 beta +/+ and IL-1 beta -/- mice. In summary, our results suggest that either IL-1 beta is not essential for the in vivo systemic response to LPS or that its role can be fulfilled by other cytokines with overlapping activities.
Fantuzzi
G
G
Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA.
Zheng
H
H
Faggioni
R
R
Benigni
F
F
Ghezzi
P
P
Sipe
J D
JD
Shaw
A R
AR
Dinarello
C A
CA
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D000685:Serum Amyloid A Protein / Q000378:metabolism
D001786:Blood Glucose; D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D000685:Serum Amyloid A Protein; D003345:Corticosterone