IL-18 is essential for the development of autoimmune disease in MRL-Fas^<lpr> mice.

在遭受自身免疫破坏的MRL-Fas和lt；LPR&GT；小鼠的肾脏中，许多细胞因子增加。已知的启动或促进mrl-Fas和lpr&gt；小鼠肾损伤的特定细胞因子是干扰素-γ。另一方面，IL-18被认为是干扰素-γ的免疫因子。因此，为了检测IL-18对MRL-Fas和lt；LPR&GT；小鼠肾脏损伤的影响，我构建了一个IL-18受体缺陷株。缺乏IL-18受体的MRL-Fas^&lt；LPR&GT；小鼠不会出现肾脏病理或蛋白尿，存活时间更长。与野生型小鼠相比，肾内干扰素-γ、IL-2和IL-12保持在正常水平。IL-18受体缺陷的MRL-Fas^&lt；LPR&GT；小鼠不会产生自身抗体和肾内免疫球蛋白沉积。我们的研究结果表明，IL=18在自身免疫性狼疮的发病机制中起关键作用。

Many cytokines are increased in the kidneys undergoing autoimmune destruction in MRL-Fas^<lpr> mice. The specific cytokine known to initiate or promote kidney injury in MRL-Fas^<lpr> mice is IFN-γ. On the other hand, IL-18 is known to be a IFN-γ iuducible factor. Thus, to examine the impact of IL-18 on renal injury in MRL-Fas^<lpr> mice, I constructed a IL-18 receptor deficient strain. MRL-Fas^<lpr> mice lacking IL-18 receptor do not develop kidney pathology, or proteinuria, and survive longer. Intrarenal IFN-γ, IL-2, and IL-12 remained at normal levels compared with wild-type mice. IL-18 receptor deficient MRL-Fas^<lpr> mice do not develop autoantibodies and intrarenal IgG deposit. Our findings demonstrate that IL=18 is critical to pathogenesis of autoimmune lupus.