Interleukin-18 and the pathogenesis of inflammatory diseases

• Published in: Seminars in nephrology Vol. 27; no. 1; p. 98
• Main Author: Dinarello, Charles A
• Format: Journal Article
• Language: English
• Published: United States 01.01.2007
• Subjects: Animals; Antibodies - immunology; Caspase 1 - physiology; Humans; Inflammation - etiology; Insulin Resistance; Intercellular Signaling Peptides and Proteins - metabolism; Interleukin-18 - antagonists & inhibitors; Interleukin-18 - immunology; Interleukin-18 - physiology; Lymphohistiocytosis, Hemophagocytic - immunology; Purinergic P2 Receptor Antagonists; Receptors, Interleukin-18 - antagonists & inhibitors; Receptors, Purinergic P2X7; Th1 Cells - immunology; Th2 Cells - immunology
• ISSN: 0270-9295
• DOI: 10.1016/j.semnephrol.2006.09.013

Several autoimmune diseases are thought to be mediated in part by interleukin (IL)-18. Many are those with associated increased interferon-gamma (IFNgamma) levels such as systemic lupus erythematosus, macrophage activation syndrome, rheumatoid arthritis, Crohn's disease, psoriasis, and graft-versus-host disease. In addition, ischemia, including acute renal failure in human beings, appears to involve IL-18. Animal studies also support the concept that IL-18 is a key player in models of lupus erythematosus, atherosclerosis, graft-versus-host disease, 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-1beta and IL-18 are related closely, and both require the intracellular cysteine protease caspase-1 for biological activity. The IL-18 binding protein, a naturally occurring and 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 to IL-18, soluble IL-18 receptors, and anti-IL-18 receptor monoclonal antibodies.