title: Loss of interleukin 33 expression in colonic crypts - a potential marker for disease remission in ulcerative colitis.
abstract: Interleukin 33 (IL-33) is a cytokine preferentially elevated in acute ulcerative colitis (UC), inferring a role in its pathogenesis. The role of IL-33 in intestinal inflammation is incompletely understood, with both pro-inflammatory and regulatory properties described. There are also conflicting reports on cellular sources and subcellular location of IL-33 in the colonic mucosa, justifying a closer look at IL-33 expression in well-defined clinical stages of UC. A total of 50 study participants (29 UC patients and 21 healthy controls) were included from a prospective cohort of inflammatory bowel disease patients treated to disease remission with infliximab, a tumour necrosis factor alpha (TNF) inhibitor. To our knowledge this is the first study examining mucosal IL-33 expression before and after anti-TNF therapy. In colonic mucosal biopsies we found a 3-fold increase in IL-33 gene expression comparing acute UC to healthy controls (p < 0.01). A significant reduction of IL33 between acute UC and disease remission was observed when TNF normalised in the mucosa (p = 0.02). Immunostaining revealed IL-33 in the nuclei of epithelial cells of scattered colonic crypts in acute disease, while at disease remission, IL-33 was undetectable, a novel finding suggesting that enterocyte-derived IL-33 is induced and maintained by inflammatory mediators.
authors.affiliation: Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, and the University Hospital of North Norway, Tromsø, Norway.
authors.forename: Mona Dixon
authors.initials: MD
authors.lastname: Gundersen
authors.affiliation: Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, and the University Hospital of North Norway, Tromsø, Norway.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Goll
authors.affiliation: Dept. of Pathology and Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hol
authors.affiliation: Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, and the University Hospital of North Norway, Tromsø, Norway.
authors.forename: Trine
authors.initials: T
authors.lastname: Olsen
authors.affiliation: Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, and the University Hospital of North Norway, Tromsø, Norway.
authors.forename: Renathe
authors.initials: R
authors.lastname: Rismo
authors.affiliation: Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, and the University Hospital of North Norway, Tromsø, Norway.
authors.forename: Sveinung W
authors.initials: SW
authors.lastname: Sørbye
authors.affiliation: Dept. of Pathology and Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Sundnes
authors.affiliation: Dept. of Pathology and Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Guttorm
authors.initials: G
authors.lastname: Haraldsen
authors.affiliation: Research Group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, and the University Hospital of North Norway, Tromsø, Norway.
authors.forename: Jon
authors.initials: J
authors.lastname: Florholmen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D000067596:Interleukin-33 / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D000067596:Interleukin-33; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha