title: Intestinal expression of the anti-inflammatory interleukin-1 homologue IL-37 in pediatric inflammatory bowel disease.
abstract: OBJECTIVE
  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.
authors.affiliation: *Department of Pediatrics †Department of Pediatric Surgery, Dr von Hauner Children's Hospital ‡Institute of Pathology, Ludwig Maximilians University, Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Weidlich
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Bulau
authors.forename: Tobias
authors.initials: T
authors.lastname: Schwerd
authors.forename: Johanna
authors.initials: J
authors.lastname: Althans
authors.forename: Roland
authors.initials: R
authors.lastname: Kappler
authors.forename: Sibylle
authors.initials: S
authors.lastname: Koletzko
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.forename: Philip
authors.initials: P
authors.lastname: Bufler
mesh_terms: D000293:Adolescent; D002648:Child; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C508587:IL37 protein, human; D018836:Inflammation Mediators; D007375:Interleukin-1; D020381:Interleukin-17; D020382:Interleukin-18; D012333:RNA, Messenger