Targeting IL-23 in Crohn's disease.

INTRODUCTION: Interleukin (IL)-23, a cytokine produced by antigen presenting cells, targets both T cells and non-T cell types with the downstream effect of enhancing inflammatory pathways. Genome-wide association studies and data from human and mouse models of intestinal inflammation support the pathogenic role of IL-23 in Crohn's disease (CD), an immune-mediated disorder that can involve any part of the gastrointestinal tract. Areas covered: This review summarizes the available data on the role of IL-23 in CD and discusses the therapeutic relevance of blocking the function of IL-23 in this disorder. Expert commentary: The use of biologic drugs, such as anti-TNF and anti-integrins, has largely improved the management of CD patients. However, a significant proportion of CD patients taking these drugs continue to experience symptoms and have inflammation in the gut, thus suggesting a need for new agents, which block other inflammatory signals. Data emerging from trials with IL-23p40 and p19 blockers indicate that IL-23 is a valid therapeutic target. More studies are needed to optimize the therapeutic regimens, ascertain whether selective inhibition of IL-23p19 is more advantageous than blockade of p40, a subunit shared by IL-12 and IL-23, and evaluate the long-term risk of these approaches.