Targeting IL-23 and Th17-Cytokines in Inflammatory Bowel Diseases

Over the last 15 years, the use of various biological therapies has largely improved the way we manage patients with Inflammatory Bowel Diseases (IBDs). Blockade of cytokine synthesis and/or activity is at the forefront of this new era with the success of inhibitors of tumor necrosis factor (TNF)-α. These therapies are however not effective in all IBD patients and efficacy may wane. Moreover, patients treated with anti-TNF-α antibodies can develop severe side-effects and new immune-mediated diseases. Therefore, a new challenge is to elucidate new inflammatory networks in the IBD tissue and develop novel anti-cytokine compounds, which may act in patients who are resistant to or cannot receive anti-TNF-α therapies. In this article we review the available data supporting the pathogenic role of IL-23 and Th17-related cytokines in IBD, and discuss whether and how compounds that control the activity of these cytokines may enter into the therapeutic armamentarium of IBD. Keywords: IL-23, Th17, IL-17A, IL-21, IBD, Th17-Cytokines, Inflammatory Bowel Diseases, tumor necrosis factor, anti-TNF- antibodies, Crohn's disease, ulcerative colitis, anti-cytokine therapy, interleukin, CD4 cells, interferon, T cells, IL-12, retinoic acid-related orphan receptor, chemokines, polymorphisms, granulocytes, trinitrobenzenesulfonic acid, TNBS-colitis, SCID mice, Bacteroides fragilis, tumours, Neutralization, ABT-874, monoclonal antibody, homeostasis