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

Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11008-13. doi: 10.1073/pnas.93.20.11008.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Endotoxemia / physiopathology*
  • Gene Expression
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / metabolism
  • Interleukin-1 / physiology*
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / immunology
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Sialoglycoproteins / physiology*
  • Survival Analysis

Substances

  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • Sialoglycoproteins