Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases.
Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases.
复制标题
抗肿瘤坏死因子抗体在炎症性肠病中的作用机理。
DOI：
10.3748/wjg.v22.i42.9300
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发表时间：
2016-11-14
影响因子：
4.3
通讯作者：
Atreya R
中科院分区：
文献类型：
--
作者：
Billmeier U;Dieterich W;Neurath MF;Atreya R
抗肿瘤坏死因子（TNF）抗体已成功用于治疗炎症性肠病（IBD）。然而，这些药物的分子作用机制仍然是一个有争议的问题。除了中和TNF，对肠屏障功能的影响，诱导粘膜免疫细胞凋亡，形成调节性巨噬细胞以及其他免疫调节特性已被讨论为中心特征。然而，临床上有效的抗TNF抗体在体内和体外的作用模式不同。此外，抗TNF剂依那西普在类风湿性关节炎的治疗中是有效的，但在克罗恩病患者中未能诱导临床应答，这表明TNF在这些炎性疾病的发病机制中的不同贡献。在下文中，我们将综述抗TNF药物作用机制的不同方面，并分析每种抗TNF药物的比较不同的作用，如TNF中和，免疫系统的调节，反向信号传导和诱导细胞凋亡。我们讨论的相关性的膜结合形式的TNF相比，可溶性形式的炎症性肠病的免疫发病机制。此外，我们审查报告，可能导致个性化的医疗方法与抗肿瘤坏死因子抗体治疗慢性肠道炎症，通过预测治疗反应。
Anti-tumor necrosis factor (TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases (IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNF, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNF antibodies were shown to differ in their mode-of-action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn’s disease patients, suggesting different contributions of TNF in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNF agents in general and analyze comparatively different effects of each anti-TNF agent such as TNF neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membrane-bound form of TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with anti-TNF antibodies in chronic intestinal inflammation, by predicting response to therapy.
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作者：
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通讯作者：
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