After interleukin-12p40, are interleukin-23 and interleukin-17 the next therapeutic targets for inflammatory bowel disease?
Inflammatory bowel disease (IBD), typified by Crohn's disease and ulcerative colitis, is a common disorder characterized by recurrent and serious inflammation of the gastrointestinal tract. Recent immunologic advances have established that T cells and inflammatory cytokines play a pivotal role in the gastrointestinal inflammation of IBD. However, many cytokines not only elicit inflammation but also protect host against microbial invasion. Hence, suppression of these dual-purpose cytokines often exposes the patients to significant risk of infection. Recent research on Interleukin (IL)-23, IL-17, and IL-17 producing T cells has become the vanguard of further understanding the contribution of cytokines to autoimmune and inflammatory diseases. IL-23 is a newly discovered member of the IL-12-related cytokine family, and is primarily involved in the differentiation of pathogenic T cells characterized by their production of IL-17. IL-17 is a potent inflammatory mediator implicated in a number of autoimmune diseases. The discovery of this IL-23/IL-17-mediated inflammatory axis is having a profound impact on the elucidation of T cell-mediated pathogenesis as well as development of novel therapeutic targets. In this review, we discuss the current literature and present our recent studies on the role of IL-23 and IL-17 in the pathogenesis of IBD. Controlling the expression/production of IL-23 and IL-17 is an approach that would allow the development of a novel treatment strategy with more anti-inflammatory efficacy and potentially with less suppressive effects on host defenses.
Zhang
Zili
Z
Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA.
Hinrichs
David J
DJ
Lu
Huiying
H
Chen
Hong
H
Zhong
Wenwei
W
Kolls
Jay K
JK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology*; D053762:Interleukin-12 Subunit p40 / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053759:Interleukin-23