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J Pediatr Gastroenterol Nutr. 2010 Mar;50(3):240-50. doi: 10.1097/MPG.0b013e3181cb8f4a.

A new model of chronic hapten-induced colitis in young rats.

Author information

  • 1Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA. lfitzpatrick@psu.edu

Abstract

AIM AND OBJECTIVE:

: 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.

MATERIALS AND METHODS:

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.

RESULTS:

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)-alpha 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.

CONCLUSIONS:

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.

PMID:
20118800
[PubMed - indexed for MEDLINE]
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