Editorial
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2018; 24(36): 4093-4103
Published online Sep 28, 2018. doi: 10.3748/wjg.v24.i36.4093
Interleukin 12/interleukin 23 pathway: Biological basis and therapeutic effect in patients with Crohn's disease
Ioanna Aggeletopoulou, Stelios F Assimakopoulos, Christos Konstantakis, Christos Triantos
Ioanna Aggeletopoulou, Christos Konstantakis, Christos Triantos, Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, Patras 26504, Greece
Stelios F Assimakopoulos, Department of Internal Medicine, University Hospital of Patras, Patras 26504, Greece
Author contributions: Aggeletopoulou I and Konstantakis C were responsible for the literature review and analysis; Aggeletopoulou I, Assimakopoulos SF and Triantos C were responsible for the drafting of the manuscript and the data interpretation; Assimakopoulos SF and Triantos C were responsible for the revision of the manuscript for important intellectual content; all authors issued final approval for the version to be submitted.
Conflict-of-interest statement: Not related to this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Christos Triantos, PhD, Assistant Professor in Internal Medicine and Gastroenterology, Department of Gastroenterology, University Hospital of Patras, D. Stamatopoulou 4, Patras 26504, Greece. chtriantos@upatras.gr
Telephone: +30-69-72894651 Fax: +30-26-10625382
Received: July 16, 2018
Peer-review started: July 16, 2018
First decision: July 31, 2018
Revised: August 2, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: September 28, 2018
Processing time: 72 Days and 19.2 Hours
Abstract

Considering that both innate and adaptive immune responses are involved in the pathogenesis of Crohn’s disease (CD), novel therapeutic options have significantly been developed. Biological agents represent an important addition to the conventional treatments for immuno-inflammatory conditions, acting as antagonists of adhesion molecules or various inflammatory cytokines. The interleukin 12 (IL-12)/IL-23 common pathway has been found to play a determinant role in the induction of inflammation in adaptive immune responses. In particular, IL-23 promotes the differentiation of naïve T helper cells into Th17 phenotype with the concomitant secretion of several inflammatory cytokines such as IL-17 and IL-22, whereas IL-12 induces the Th1 polarization and production of critical cytokines such as interferon-γ and tumor necrosis factor. Nowadays, there is increased interest regarding the role of IL-23 as a therapeutic target of CD through the blockage of IL-23 mediated pathways. In this editorial, we focus on the role of IL-12/IL-23 pathway in the regulation of mucosal immunity and in the induction and maintenance of chronic inflammation. In parallel, we critically discuss the available data regarding the therapeutic effect of the IL-12/IL-23 inhibitors and especially of ustekinumab, a human monoclonal antibody which has been recently approved by the United States Food and Drug Administration for the management of moderate-to-severe CD and its potential to be used as first-line therapy in everyday clinical practice.

Keywords: Crohn’s disease; Interleukin 12; Interleukin 23; Monoclonal antibodies; Ustekinumab; Biological agents; Interleukin 12/interleukin 23 blockade

Core tip: The therapeutic management of Crohn’s disease patients not responding to treatment with anti-tumor necrosis factor agents remains a clinical challenge. Recently, there has been increased evidence regarding the development of new drugs with alternative mechanisms of action. Interleukin (IL)-12 and IL-23 are important cytokines which are involved in the adaptive immune responses and their common pathway has been found to play a determinant role in the induction of inflammation. Clinical trials have assessed the therapeutic effect of an IL-12/IL-23 inhibitor (ustekinumab), demonstrating rapid clinical effect with a safety profile. Further studies are needed to elucidate its potential role as first-line therapy in Crohn’s disease.