Hapten‐induced colitis associated with maintained Th1 and inflammatory responses in IFN‐γ receptor‐deficient mice

IFN‐γ is a potent pro‐inflammatory cytokine thought to be involved in the pathogenesis of Crohn's disease. To further define the role of IFN‐γ in intestinal inflammation, we studied the effects of intra‐colonic 2,4,6‐trinitrobenzene sulfonic acid (TNBS) instillation in mice with a functionally inactivated IFN‐γ receptor 1 (IFN‐γR1– / –). Our results indicate that IFN‐γ is not necessary for the induction of hapten‐induced colitis: after TNBS administration both wild‐type and IFN‐γR1– / – mice lost body weight, and the histological features of TNBS‐induced colitis were comparable. Colons of IFN‐γR1– / – mice contained a greater number of cells, represented by macrophages and CD4+ T cells; caudal lymph node cells produced more IFN‐γ and TNF‐α upon stimulation in vitro. Moreover, IL‐18 and IL‐12 p40 RNA levels were comparably up‐regulated after TNBS treatment in IFN‐γR1– / – wild‐type mice. These findings demonstrate that IFN‐γ is dispensable for the development of TNBS‐induced colitis. Importantly, the production of Th1 cytokines (e. g. IFN‐γ and TNF‐α) by caudal lymph node T lymphocytes was enhanced rather than decreased in IFNγR1– / – mice with no evidence for default Th2 development.