Interleukin-18 and the pathogenesis of inflammatory diseases

Semin Nephrol. 2007 Jan;27(1):98-114. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 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


  • 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