Journal article
Rapid development of colitis in NSAID-treated IL-10–deficient mice
Gastroenterology (New York, N.Y. 1943), Vol.123(5), pp.1527-1542
11/2002
DOI: 10.1053/gast.2002.1231527
PMID: 12404228
Abstract
Background & Aims: Interleukin (IL)-10 is an anti-inflammatory and immune regulatory cytokine. IL-10–deficient mice (IL-10−/−) develop chronic inflammatory bowel disease (IBD), indicating that endogenous IL-10 is a central regulator of the mucosal immune response. Prostaglandins are lipid mediators that may be important mediators of intestinal inflammation. In this study we assessed the role of prostaglandins in the regulation of mucosal inflammation in the IL-10−/− mouse model of IBD. Methods: Prostaglandin (PG) synthesis was inhibited with nonselective or cyclooxygenase (COX)-isoform selective inhibitors. Severity of inflammation was assessed histologically. Cytokine production was assessed by ribonuclease protection analysis and enzyme-linked immunosorbent assay. PGE2 levels were assessed by enzyme immunoassay. COX-1 and COX-2 expression was assessed by Western blot analysis. Results: Nonsteroidal anti-inflammatory drug (NSAID) treatment of wild-type mice had minimal effect on the colon. In contrast, NSAID treatment of 4-week-old IL-10−/− mice resulted in rapid development of colitis characterized by infiltration of the lamina propria with macrophages and interferon gamma–producing CD4+ T cells. Colitis persisted after withdrawal of the NSAID. NSAID treatment decreased colonic PGE2 levels by 75%. Treatment of IL-10−/− mice with sulindac sulfone (which does not inhibit PG production) did not induce colitis whereas the NSAID sulindac induced severe colitis. COX-1– or COX-2–selective inhibitors used alone did not induce IBD in IL-10−/− mice. However, the combination of COX-1– and COX-2–selective inhibitors did induce colitis. Conclusions: NSAID treatment of IL-10−/− mice results in the rapid development of severe, chronic IBD. Endogenous PGs are important inhibitors of the development of intestinal inflammation in IL-10−/− mice.
GASTROENTEROLOGY 2002;123:1527-1542
Details
- Title: Subtitle
- Rapid development of colitis in NSAID-treated IL-10–deficient mice
- Creators
- Daniel J Berg - Department of Internal MedicineJuan Zhang - Department of Internal MedicineJoel V Weinstock - Department of Internal MedicineHanan F Ismail - Department of Internal MedicineKeith A Earle - Cell Pathways, Horsham, PennsylvaniaHector Alila - Cell Pathways, Horsham, PennsylvaniaRifat Pamukcu - Cell Pathways, Horsham, PennsylvaniaSteven Moore - Department of Pathology, University of Iowa College of Medicine, Iowa City, IowaRichard G Lynch - Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Gastroenterology (New York, N.Y. 1943), Vol.123(5), pp.1527-1542
- Publisher
- Elsevier Inc
- DOI
- 10.1053/gast.2002.1231527
- PMID
- 12404228
- ISSN
- 0016-5085
- eISSN
- 1528-0012
- Language
- English
- Date published
- 11/2002
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
- Record Identifier
- 9984046819202771
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