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 C57B1/6 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.