Interleukin-12 (IL-12) and interleukin-23 (IL-23), which belong to the IL-12 family of cytokines, have a key role in intestinal homeostasis and inflammation and are implicated in the pathogenesis of inflammatory bowel disease. Upon their secretion by antigen-presenting cells, they exert both pro-inflammatory and anti-inflammatory receptor-mediated effects. An increased understanding of these biological effects, particularly the pro-inflammatory effects mediated by IL-12 and IL-23, has led to the development of monoclonal antibodies that target a subunit common to IL-12 and IL-23 (p40; targeted by ustekinumab and briakinumab), or the IL-23-specific subunit (p19; targeted by risankizumab, guselkumab, brazikumab and mirikizumab). This Review provides a summary of the biology of the IL-12 family cytokines IL-12 and IL-23, discusses the role of these cytokines in intestinal homeostasis and inflammation, and highlights IL-12- and IL-23-directed drug development for the treatment of Crohn’s disease and ulcerative colitis.
IL-12 and IL-23 have been implicated in inflammatory bowel disease. In this Review, Vande Casteele and colleagues summarize the mechanistic role of IL-12 and IL-23 in inflammatory bowel disease, and discuss the clinical development of drugs targeting IL-12 and/or IL-23.
Key points: IL-12 and IL-23, which are members of the IL-12 family of cytokines, have a key role in intestinal homeostasis and inflammation, including in inflammatory bowel disease.Multiple IL-12- and/or IL-23-neutralizing antibodies have been tested in immune-mediated diseases, including Crohn’s disease and ulcerative colitis.In addition to demonstrated efficacy for clinical, endoscopic and histological outcomes, targeting IL-12 and/or IL-23 is a safe treatment strategy.The exact positioning of such antibodies in current treatment algorithms will be influenced by ongoing head-to-head trials and evaluation of predictive molecular markers.