Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice
Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice
复制标题
DOI：
10.1073/pnas.93.20.11008
复制
发表时间：
1996-10-01
影响因子：
11.1
通讯作者：
Hirsh, D
中科院分区：
文献类型：
--
作者：
Hirsch, E;Irikura, VM;Hirsh, D
白细胞介素1受体拮抗剂（IL-1 ra）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-1 ra的生理作用，我们产生了缺乏IL-1 ra或在内源性启动子控制下过度产生IL-1 ra的小鼠。与野生型对照相比，缺乏IL-1 ra的小鼠体重降低。他们比对照组更容易感染致死性内毒素血症，但对单核细胞增生李斯特菌感染的敏感性较低。相反，IL-1 ra过度生产者受到保护，免受内毒素的致死作用，但更容易患上淋病。与对照组相比，内毒素攻击后IL-1的血清水平在IL-1 ra无效组中降低，而在IL-1 ra过度产生组中升高。这些数据表明内源性产生的IL-1 ra在生长、对感染和炎症的反应以及细胞因子表达的调节中的关键作用。
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.