- Fecal Incontinence
|IL-12 and IL-23 pathway inhibition in inflammatory bowel disease
Nat Rev Gastroenterol Hepatol. 2023 Apr 17. doi: 10.1038/s41575-023-00768-1.Online ahead of print.
Alimentiv Translational Research Consortium (ATRC):
Silvio Danese, Geert D'Haens, Lars Eckmann, William A Faubion, Brian G Feagan, Vipul Jairath, Christopher Ma, Saurabh Mehandru, Julian Panes, Florian Rieder, William J Sandborn, Mark S Silverberg, Marisol Veny, Severine Vermeire, Stefania Vetrano
1University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium.
2KU Leuven Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium.
3Inflammatory Bowel Disease Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
4Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5Department of Medicine, Yale University, New Haven, CT, USA.
6Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
7Department of Medicine 1, University Erlangen-Nürnberg, Erlangen, Germany.
8Deutsches Zentrum Immuntherapie DZI, University Erlangen-Nürnberg, Erlangen, Germany.
9Department of Medicine, University of California San Diego, La Jolla, CA, USA. email@example.com.
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.