|Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
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.