Intestinal Expression of the Anti-Inflammatory Interleukin-1 Homologue IL-37 in Pediatric Inflammatory Bowel Disease

Weidlich, Simon*; Bulau, Ana-Maria*; Schwerd, Tobias*; Althans, Johanna; Kappler, Roland; Koletzko, Sibylle*; Mayr, Doris; Bufler, Philip*

Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0000000000000387
Original Articles: Gastroenterology
Abstract

Objectives: The function of interleukin (IL)-37 has not been resolved. We recently showed that IL-37 suppresses colonic inflammation in mice. To gain more insight into its relevance in human disease, we investigated the expression of IL-37 in the intestine of pediatric patients with chronic inflammatory bowel disease (IBD).

Methods: Intestinal biopsies were obtained from children with IBD (18 Crohn disease [CD], 14 ulcerative colitis [UC] and 11 controls) during endoscopy and analyzed for IL-37 expression by immunohistochemistry and real-time polymerase chain reaction. Results were correlated with immunostaining for IL-18 and IL-17, messenger RNA (mRNA) levels of pro- and anti-inflammatory cytokines, and clinical parameters.

Results: IL-37 protein was detected in epithelial cells and submucosal lymphoid cells of patients with CD and UC as well as healthy controls. IL-37 protein expression tended to be higher with submucosal lymphoid cell infiltration of patients with CD and UC and correlated with histological severity score of inflammation. IL-18 showed a staining pattern similar to that of IL-37, whereas staining for IL-17 revealed distinct positive cells scattered in the submucosal layer. mRNA expression of IL-8, IL-17, and IL-10 was upregulated in patients with CD and UC. mRNA levels of IL-18 and IL-37 were not significantly elevated compared with controls. Levels of IL-37 and IL-18 mRNA showed a positive correlation in the CD group.

Conclusions: IL-37 protein is expressed in healthy and diseased bowel tissue. IL-37 and IL-18 show a similar expression pattern and correlate at mRNA levels. Future studies are warranted to delineate the specific contribution of IL-37 to modulate chronic bowel inflammation in humans.

Author Information

*Department of Pediatrics

Department of Pediatric Surgery, Dr von Hauner Children's Hospital

Institute of Pathology, Ludwig Maximilians University, Munich, Germany.

Address correspondence and reprint requests to Prof Dr Philip Bufler, Dr von Hauner Children's Hospital, Lindwurmstr. 4, 80337 München, Germany (e-mail: Philip.Bufler@med.uni-muenchen.de).

Received 20 November, 2013

Accepted 27 March, 2014

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).

This article contains parts of the doctoral thesis of Simon Weidlich.

This work was supported by Deutsche Forschungsgemeinschaft (BU 1222/3-3 to P.B.) and Ludwig-Maximilians-University Munich (FöFoLe 24/2010 to S.W./P.B.).

P.B. holds a patent on the application of IL-1F7b (IL-37b) (US 7279155 B2). The other authors report no conflicts of interest.

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,