IL-18 (also referred to as IL-1?) has been shown to augment the secretion of IFN-? from T lymphocytes and to increase NK cell activity in spleen cells. IL-18 exhibits 19% and 12% identity with IL-1? and IL-?, respectively, over the twelve ?-strands of the ?-trefoil fold domain, which is a signature feature of the IL-1 family. The unusual leader sequence of IL-18 may be analogous to the IL-1? pro-domain, which must be cleaved by the serine protease ICE for optimal secretion and biological activity. IL-18, which was originally described as IGIF (IFN-?-inducing factor), IL-18 is induced in mouse liver subsequent to challenge with lipopolysaccharide (LPS). IL-18 binding protein (IL-18BP) functions as an inhibitor of the early Th1 response by binding to IL-18 and inhibiting IFN-? production. IL-18BP is a member of the immunoglobulin superfamily and shares some homology to IL-1RII.