Journal of Pediatric Gastroenterology and Nutrition. 50(3):240–250, MAR 2010
DOI: 10.1097/MPG.0b013e3181cb8f4a
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PMID: 20118800
Issn Print: 0277-2116
Publication Date: 2010/03/01
A New Model of Chronic Hapten-induced Colitis in Young Rats
Leo Fitzpatrick;Katia Meirelles;Jeffrey Small;Frances Puleo;Walter Koltun;Robert Cooney;
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*Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA†Children's Hospital, Boston, MA, USA‡Department of Surgery, Penn State College of Medicine, USA.
Abstract
Chronic models of inflammatory bowel disease are lacking in preadult rodents. The primary goal of our study was to develop a chronic model of hapten-induced intestinal inflammation and fibrosis in young rats. Second, we aimed to determine the profiles of key Th-1, Th-2, and Th-17 proinflammatory and profibrotic cytokines, during the progression of colitis in young rats.Chronic hapten-induced colitis was induced by the administration of intracolonic 2,4,6-trinitrobenzene sulfonic acid (TNBS) in young Wistar rats (postnatal days 23, 35, 48, and 59). After 1, 3, or 4 cycles of TNBS, rats were euthanized and the colons were removed for the measurement of macroscopic, histologic, and biochemical parameters of colitis.Young rats developed moderate to severe colitis in the distal colon, without significant morbidity or mortality. Macroscopic severity, histologic pathology, and colonic weights increased progressively with repeated TNBS administration. Cobblestone-like ulceration and fibrosis was evident in the colon, particularly after 4 cycles of TNBS. There was a unique cytokine pattern associated with colitis in young rats. Interleukin (IL)-12 and tumor necrosis factor (TNF)-α peaked during the earlier postnatal time points (days 28 and 54) and then declined after repetitive administration of the hapten (day 67). In contrast, IL-13 and IL-17 were consistently elevated after administration of TNBS to the colon of young rats.A new model of colitis was established in young rats, which has a unique pattern of Th-1, Th-2, and Th-17 cytokine induction. This chronic TNBS model may be useful for studying the development of inflammation and fibrosis in preadult animals.
