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

• Project/Area Number: 13670484
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 内科学一般
• Research Institution: Kinki University
• Principal Investigator: KINOSHITA Koji Kinki University, School of Medicine, assistant professor, 医学部, 講師 (70247980)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥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)
• Keywords: Systemic lupus erythematosus / IL-18 / Lupus nephritis / マウス

Research Abstract

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.