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

Leo R. Fitzpatrick, Katia Meirelles, Jeffrey S. Small, Frances Puleo, Walter Koltun, Robert N. Cooney

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Aim and Objectives: 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)-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. 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.

Original languageEnglish (US)
Pages (from-to)240-250
Number of pages11
JournalJournal of pediatric gastroenterology and nutrition
Volume50
Issue number3
DOIs
StatePublished - Mar 1 2010

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Gastroenterology

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