Interleukin-18 and the pathogenesis of inflammatory diseases.

Abstract

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.

• Authors: Charles A Dinarello
• Journal: Seminars in nephrology (Semin Nephrol) Vol. 27 Issue 1 Pg. 98-114 (Jan 2007) ISSN: 0270-9295 [Print] United States
• PMID: 17336692 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antibodies
• Intercellular Signaling Peptides and Proteins
• Interleukin-18
• P2RX7 protein, human
• Purinergic P2 Receptor Antagonists
• Receptors, Interleukin-18
• Receptors, Purinergic P2X7
• interleukin-18 binding protein
• Caspase 1

Topics

• Animals
• Antibodies (immunology)
• Caspase 1 (physiology)
• Humans
• Inflammation (etiology)
• Insulin Resistance
• Intercellular Signaling Peptides and Proteins (metabolism)
• Interleukin-18 (antagonists & inhibitors, immunology, physiology)
• Lymphohistiocytosis, Hemophagocytic (immunology)
• Purinergic P2 Receptor Antagonists
• Receptors, Interleukin-18 (antagonists & inhibitors)
• Receptors, Purinergic P2X7
• Th1 Cells (immunology)
• Th2 Cells (immunology)