ABSTRACT
Several autoimmune diseases are thought to be mediated, in part, by interleukin (IL)-18. Many are those with associated elevated interferon-g (IFN-g) levels such as systemic lupus erythematosus (SLE), macrophage-activation syndrome, rheumatoid arthritis (RA), Crohn’s disease, and psoriasis, as well as graft versus host disease (GVHD). In addition, ischemia, including acute renal failure in humans, appears to involve IL-18. Animal studies also support the concept that IL-18 is a key player in models of lupus erythematosus, atherosclerosis, GVHD, and hepatitis. Unexpectedly, IL-18 plays a role in appetite control and the development of obesity. IL-18 is a member of the IL-1 family; IL-1b and IL-18 are closely related, and both require the intracellular cysteine protease caspase-1 for biological activity. The IL-18 binding protein, a naturally occurring, specific inhibitor of IL-18, neutralizes IL-18 activities and has been shown to be safe in patients. Other options for reducing IL-18 activities are inhibitors of caspase-1, human monoclonal antibodies (mAbs) to IL-18, soluble IL-18 receptors, and anti-IL-18 receptor (mAbs).
