Interleukin-18 treatment options for inflammatory diseases.

Several autoimmune diseases are believed to be mediated, in part, by interleukin (IL)-18. Many are those with associated elevated interferon-gamma levels, such as systemic lupus erythematosus, macrophage activation syndrome, rheumatoid arthritis, Crohn's disease, psoriasis, as well as graft-versus-host disease. Clinical and animal studies also support the concept that IL-18 is a key player in atherosclerosis, acute renal ischemia and hepatitis. IL-18 is a member of the IL-1 family; IL-1beta and IL-18 are closely related, and both require the intracellular cysteine protease caspase-1 for biologic activity. The IL-18 binding protein, a naturally occurring, specific inhibitor of IL-18, neutralizes IL-18 activities and is likely to be safe in patients. Other options for reducing IL-18 activities are inhibitors of capsase-1, human monoclonal antibodies to IL-18, soluble IL-18 receptors and anti-IL-18 receptor monoclonal antibodies.