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Differential role of tumor necrosis factor receptors in TNBS colitis



Background: Tumor necrosis factor α (TNFα) plays a central role in the pathology of T helper 1-mediated colitis such as Crohn's disease; however, the role of its 2 receptors in mediating pathology has not been fully explored.

Methods: Trinitrobenzene sulfonic acid colitis was used to induce colitis in mice lacking each of the TNF receptors (TNFRs) and in wild-type mice. TNFR1−/− mice lost more weight, became hypothermic, and had increased mortality compared with wild-type C57Bl/6 mice. TNFR2−/− mice, however, lost less weight, had normal temperatures, and had improved survival.

Results: Despite the improved clinical outcomes in TNFR2−/− mice, TNFα levels were increased in these mice.

Conclusions: TNFα signaling through TNFR1 is protective in the trinitrobenzene sulfonic acid mouse model of inflammatory bowel disease.