Open AccessFunctions of interleukin 1 receptor antagonist in gene knockout and overproducing mice.
Author(s) -
Emmet Hirsch,
Vera M. Irikura,
Sarah Paul,
David Hirsh
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.20.11008
Subject(s) - interleukin 1 receptor antagonist , biology , receptor antagonist , cytokine , receptor , interleukin , inflammation , endogeny , cytokine receptor , listeria monocytogenes , knockout mouse , interleukin 1 receptor, type i , immunology , antagonist , endocrinology , bacteria , biochemistry , genetics
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.