Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines. Similar to IL-1β, IL-18 is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine but unlike IL-1β, the IL-18 precursor is constitutively present in nearly all cells in healthy humans and animals. The activity of IL-18 is balanced by the presence of a high affinity, naturally occurring IL-18 binding protein (IL-18BP). In humans, increased disease severity can be associated with an imbalance of IL-18 to IL-18BP such that the levels of free IL-18 are elevated in the circulation. Increasing number of studies have expanded the role of IL-18 in mediating inflammation in animal models of disease using the IL-18BP, IL-18-deficient mice, neutralization of IL-18, or deficiency in the IL-18 receptor alpha chain. A role for IL-18 has been implicated in several autoimmune diseases, myocardial function, emphysema, metabolic syndromes, psoriasis, inflammatory bowel disease, hemophagocytic syndromes, macrophage activation syndrome, sepsis, and acute kidney injury, although in some models of disease, IL-18 is protective. IL-18 plays a major role in the production of interferon-γ from T-cells and natural killer cells. The IL-18BP has been used safely in humans and clinical trials of IL-18BP as well as neutralizing anti-IL-18 antibodies are in clinical trials. This review updates the biology of IL-18 as well as its role in human disease.
Keywords: inflammation, autoimmune diseases, inflammasomes, interleukin-1, macrophages
Citation: Dinarello CA, Novick D, Kim S and Kaplanski G (2013) Interleukin-18 and IL-18 binding protein. Front. Immunol. 4:289. doi: 10.3389/fimmu.2013.00289
Received: 31 May 2013; Accepted: 04 September 2013;
Published online: 08 October 2013.
Edited by:Cecilia Garlanda, Istituto Clinico Humanitas, Italy
Reviewed by:Kingston H. Mills, Trinity College Dublin, Ireland
Copyright: © 2013 Dinarello, Novick, Kim and Kaplanski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Charles A. Dinarello, Department of Medicine, University of Colorado Denver, Denver, CO 80262, USA e-mail: firstname.lastname@example.org