Hirsch E, Irikura V M, Paul S M, Hirsh D
Department of Biochemistry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11008-13. doi: 10.1073/pnas.93.20.11008.
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.
白细胞介素1受体拮抗剂（IL-1ra）是一种细胞因子，其唯一已知的作用是竞争性抑制白细胞介素1（IL-1）与其受体的结合。为了研究内源性产生的IL-1ra的生理作用，我们培育了缺失IL-1ra或在内源性启动子控制下过量产生IL-1ra的小鼠。与野生型对照相比，缺乏IL-1ra的小鼠体重减轻。它们比对照更易死于致死性内毒素血症，但对单核细胞增生李斯特菌感染的易感性较低。相反，过量产生IL-1ra的小鼠对内毒素的致死作用有抵抗力，但对李斯特菌病更易感。与对照相比，内毒素攻击后IL-1ra基因敲除小鼠的血清IL-1水平降低，而过量产生IL-1ra的小鼠血清IL-1水平升高。这些数据表明内源性产生的IL-1ra在生长、对感染和炎症的反应以及细胞因子表达的调节中起关键作用。
