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

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*

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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.

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


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