Proinflammatory cytokines underlying the inflammation of Crohnʼs disease

Abstract

The purpose of this review is to encapsulate our current understanding of the pro-inflammatory cytokines responsible for the inflammation underlying Crohn’s disease and the prospect of using this information to devise therapy for this condition based on inhibition of these cytokines. Current research is shedding new light on the role of both Th1 and Th17 responses in the pathogenesis of Crohn’s disease. Initial studies conducted a decade ago highlighted the view that Crohn’s disease inflammation is caused by an IL-12-driven Th1 response which resulted in the generation of IFN-γ which then served as the main inflammatory mediator. In recent years, however, this view has been largely eclipsed by studies, conducted mainly in murine models, showing that a Th17 response is the main cause of Crohn’s disease inflammation through the production of IL-17. Now, a somewhat more balance view is emerging which holds that IFN-γ is still a major pro-inflammatory cytokine in Crohn’s disease although it may arise from both the Th1 and Th17 cell-mediated responses at different phases of the inflammatory process. The new findings continue to support the idea that anti-IL-12p40, an antibody that inhibits both the Th1 and Th17 response, is logically the most potent anti-cytokine for the treatment of Crohn’s disease.