IL-18 binding protein fusion construct delays the development of diabetes in adoptive transfer and cyclophosphamide-induced diabetes in NOD mouse

IL-18 is a type 1 pro-inflammatory cytokine with structural similarities to IL-1 and in synergy with IL-12 stimulates IFN-γ production from T lymphocytes and polarizes development and function of Th1 cells. Because IL-1, IFN-γ, and up-regulated Th1-mediated events are involved in the pathogenesis of both human and rodent type 1 diabetes mellitus, we have evaluated the effects of a specific inhibitor of IL-18 (the IL-18bp:FcIg) on the development of accelerated forms of autoimmune diabetes in NOD mice. The data show that prolonged prophylactic treatment with IL-18bp:FcIg significantly reduced the cumulative incidence of diabetes induced in NOD mice either by adoptive transfer of diabetogenic cells or by injection with large doses of cyclophosphamide. These data provide the first in vivo evidence for the diabetogenic role of IL-18 in immuno-inflammatory diabetogenic pathways in NOD mice.