Interleukin 12/interleukin 23 pathway: Biological basis and therapeutic effect in patients with Crohn's disease  

作　　者：Ioanna Aggeletopoulou Stelios F Assimakopoulos Christos Konstantakis Christos Triantos 

机构地区：[1]Division of Gastroenterology,Department of Internal Medicine,Medical School,University of Patras [2]Department of Internal Medicine,University Hospital of Patras

出　　处：《World Journal of Gastroenterology》2018年第36期4093-4103,共11页世界胃肠病学杂志（英文版）

摘　　要：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 na?ve 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 moderateto-severe CD and its potential to be used as first-line therapy in everyday clinical practice.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 na?ve 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 moderateto-severe CD and its potential to be used as first-line therapy in everyday clinical practice.

关 键 词：Crohn’s disease INTERLEUKIN 12 INTERLEUKIN 23 MONOCLONAL ANTIBODIES USTEKINUMAB Biological agents INTERLEUKIN 12/interleukin 23 BLOCKADE 

分 类 号：R57[医药卫生—消化系统]