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Mediators of Inflammation
Volume 2013, Article ID 608187, 11 pages
Review Article

The Role of IL-33 in Gut Mucosal Inflammation

1Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
2Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy
3Department of Biomedical Sciences for Health, University of Milan School of Medicine, 20122 Milan, Italy

Received 4 January 2013; Accepted 9 May 2013

Academic Editor: Eduardo Arranz

Copyright © 2013 Luca Pastorelli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Interleukin (IL)-33 is a recently identified cytokine belonging to the IL-1 family that is widely expressed throughout the body and has the ability to induce Th2 immune responses. In addition, IL-33 plays a key role in promoting host defenses against parasites through the expansion of a novel population of innate lymphoid cells. In recent years, a growing body of evidence has shown that the proinflammatory properties displayed by IL-33 are detrimental in several experimental models of inflammation; in others, however, IL-33 appears to have protective functions. In 2010, four different research groups consistently described the upregulation of IL-33 in patients with inflammatory bowel disease (IBD). Animal models of IBD were subsequently utilized in order to mechanistically determine the precise role of IL-33 in chronic intestinal inflammation, without, however, reaching conclusive evidence demonstrating whether IL-33 is pathogenic or protective. Indeed, data generated from these studies suggest that IL-33 may possess dichotomous functions, enhancing inflammatory responses on one hand and promoting epithelial integrity on the other. This review focuses on the available data regarding IL-33/ST2 in the physiological and inflammatory states of the gut in order to speculate on the possible roles of this novel IL-1 family member in intestinal inflammation.