Differential Role of Tumor Necrosis Factor Receptors in TNBS Colitis

BACKGROUND: Tumor necrosis factor alpha (TNFalpha) 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, TNFalpha levels were increased in these mice. CONCLUSIONS: TNFalpha signaling through TNFR1 is protective in the trinitrobenzene sulfonic acid mouse model of inflammatory bowel disease.