| First Author | Spencer DM | Year | 2002 |
| Journal | Gastroenterology | Volume | 122 |
| Issue | 1 | Pages | 94-105 |
| PubMed ID | 11781285 | Mgi Jnum | J:73628 |
| Mgi Id | MGI:2156111 | Doi | 10.1053/gast.2002.30308 |
| Citation | Spencer DM, et al. (2002) Distinct inflammatory mechanisms mediate early versus late colitis in mice. Gastroenterology 122(1):94-105 |
| abstractText | BACKGROUND & AIMS: Progression from the acute to chronic phase of inflammatory bowel disease cannot be easily evaluated in patients and has not been characterized in animal models. We report a longitudinal study investigating changes in the mucosal immune response in an experimental model of colitis. METHODS: Severity of colitis, body mass, stool consistency and blood content, serum amyloid A, and tissue histology were examined in interleukin (IL)-10-deficient mice over 35 weeks. The corresponding production of IL-12, IL-18, interferon gamma, tumor necrosis factor alpha, IL-4, and IL-13 by lamina propria mononuclear cells in the inflamed intestine was measured. Administration of neutralizing antibody to IL-12 at distinct times during disease progression permitted evaluation of its therapeutic potential. RESULTS: The clinical manifestations and intestinal inflammation delineated an early phase of colitis (10-24 weeks), characterized by a progressive increase in disease severity, followed by a late phase (>25 weeks), in which chronic inflammation persisted indefinitely. Lamina propria mononuclear cells from mice with early disease synthesized progressively greater quantities of IL-12 and interferon gamma, whereas production of both cytokines dramatically declined and returned to pre-disease levels in the late phase of colitis. Consistent with this pattern, neutralizing antibody to IL-12 reversed early, but not late, disease. In contrast, IL-4 and IL-13 production increased progressively from pre- to early to late disease. CONCLUSIONS: Colitis that develops in IL-10-deficient mice evolves into 2 distinct phases. IL-12 plays a pivotal role in early colitis, whereas its absence and the synthesis of IL-4 and IL-13 in late disease indicate that other immune mechanisms sustain chronic inflammation. |
