Interleukin-18 and the pathogenesis of inflammatory diseases.
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.
Dinarello
Charles A
CA
Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, CO, USA.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D020170:Caspase 1 / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000276:immunology; D058919:Purinergic P2 Receptor Antagonists; D053724:Receptors, Interleukin-18 / Q000037:antagonists & inhibitors; D058486:Receptors, Purinergic P2X7; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000906:Antibodies; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C546468:P2RX7 protein, human; D058919:Purinergic P2 Receptor Antagonists; D053724:Receptors, Interleukin-18; D058486:Receptors, Purinergic P2X7; C118370:interleukin-18 binding protein; D020170:Caspase 1