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Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11008-13.

Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice.

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  • 1Department of Biochemistry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.

Abstract

Interleukin 1 receptor antagonist (IL-1ra) is a cytokine whose only known action is competitive inhibition of the binding of interleukin 1 (IL-1) to its receptor. To investigate the physiological roles of endogenously produced IL-1ra, we generated mice that either lack IL-1ra or overproduce it under control of the endogenous promoter. Mice lacking IL-1ra have decreased body mass compared with wild-type controls. They are more susceptible than controls to lethal endotoxemia but are less susceptible to infection with Listeria monocytogenes. Conversely, IL-1ra overproducers are protected from the lethal effects of endotoxin but are more susceptible to listeriosis. Serum levels of IL-1 following an endotoxin challenge are decreased in IL-1ra nulls and increased in IL-1ra overproducers in comparison to controls. These data demonstrate critical roles for endogenously produced IL-1ra in growth, responses to infection and inflammation, and regulation of cytokine expression.

PMID:
8855299
PMCID:
PMC38274
[PubMed - indexed for MEDLINE]
Free PMC Article
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