Lessons Learned From Trials Targeting Cytokine Pathways in Patients With Inflammatory Bowel Diseases.
Lessons Learned From Trials Targeting Cytokine Pathways in Patients With Inflammatory Bowel Diseases.
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DOI：
10.1053/j.gastro.2016.10.018
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发表时间：
2017-02
期刊：
影响因子：
29.4
通讯作者：
Sandborn WJ
中科院分区：
文献类型：
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作者：
Abraham C;Dulai PS;Vermeire S;Sandborn WJ
深入了解炎症性肠病（IBD）的发病机制为治疗方法的发展提供了重要信息。IBD患者炎症肠组织中白细胞介素23 （il - 23）和辅助性t - 17细胞通路分子水平升高。白细胞介素23受体基因（IL23R）的功能变异丧失可预防IBD，在动物中，阻断IL23可降低结肠炎的严重程度。这些发现表明，il - 23和Th17细胞通路可能是治疗IBD的有希望的靶点。临床试验研究了针对不同水平il - 23和Th17细胞通路的药物的作用，结果为IBD的发病机制和调节这些通路的额外策略提供了见解。更广泛地降低促炎细胞因子水平和增加抗炎机制的策略也出现在IBD的治疗中。针对这些免疫系统途径的试验结果为未来的试验提供了重要的经验教训。研究结果表明，改进方法将患者特征和反应的生物标志物与治疗方法的选择结合起来是很重要的。
Insights into the pathogenesis of inflammatory bowel diseases (IBD) have provided important information for the development of therapeutics. Levels of interleukin 23 (IL23) and T-helper (Th) 17 cell pathway molecules are elevated in inflamed intestinal tissues of patients with IBD. Loss of function variants of the interleukin 23 receptor gene (IL23R) protect against IBD, and in animals, blocking IL23 reduces severity of colitis. These findings indicated that the IL23 and Th17 cell pathways might be promising targets for treatment of IBD. Clinical trials have investigated the effects of agents designed to target distinct levels of the IL23 and Th17 cell pathways, and the results are providing insights into IBD pathogenesis and additional strategies for modulating these pathways. Strategies to reduce levels of proinflammatory cytokines more broadly and increase anti-inflammatory mechanisms are also emerging for treatment of IBD. The results from trials targeting these immune system pathways have provided important lessons for future trials. Findings indicate the importance of improving approaches to integrate patient features and biomarkers of response with selection of therapeutics.