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溃疡性结肠炎的生物治疗:抗 TNF 之后是什么。

Biological therapy for ulcerative colitis: what is after anti-TNF.

机构信息

IBD Center, Gastroenterology, IRCCS Humanitas, Rozzano, Milan, Italy.

出版信息

Curr Drug Targets. 2011 Sep;12(10):1433-9. doi: 10.2174/138945011796818225.

Abstract

Ulcerative Colitis (UC) is an idiopathic chronic inflammation. Its etiology is still largely unknown. Environmental and genetic factors in combination with the microbial flora or specific microorganisms are thought to trigger the gut inflammation, leading to the activation of the intestinal immune response. Immune and non-immune cells create a cross talk via the secretion of soluble mediators and expression of cell adhesion molecules, resulting in further cell activation. Mediators such as cytokines and chemokines play a key role in cell recruitment and polarization, intercellular signal amplification or activation and differentiation. Lack of balance between pro-inflammatory and anti-inflammatory cytokines is crucial in the pathogenesis of IBD. Conventional therapy of UC quite commonly fails to avoid complications or colectomy and the therapeutic armamentarium remains still limited. New therapeutic options, such as, biological therapy, gene therapy, hematopoietic stem cell transplantation, and leucoapheresis, have been investigated recently. Biological therapy is focused on different targets involved in the inflammatory process. Several new biological drugs have been introduced in the last decade or are under investigation for the treatment of IBD. They include anti TNF-α agents, anti adhesion molecules, anti IL-12/23, anti IL-6R and more. We review the recent advances in biological therapy for UC treatment beyond the anti-TNFs.

摘要

溃疡性结肠炎(UC)是一种特发性慢性炎症。其病因在很大程度上仍然未知。环境和遗传因素与微生物菌群或特定微生物一起被认为会引发肠道炎症,从而导致肠道免疫反应的激活。免疫细胞和非免疫细胞通过可溶性介质的分泌和细胞黏附分子的表达进行交叉对话,导致进一步的细胞激活。细胞因子和趋化因子等介质在细胞募集和极化、细胞间信号放大或激活和分化中起着关键作用。促炎细胞因子和抗炎细胞因子之间的失衡在 IBD 的发病机制中至关重要。UC 的常规治疗相当常见,无法避免并发症或结肠切除术,治疗手段仍然有限。最近已经研究了新的治疗选择,如生物治疗、基因治疗、造血干细胞移植和白细胞去除术。生物治疗的重点是涉及炎症过程的不同靶点。过去十年中引入了几种新的生物药物,或正在研究用于治疗 IBD。它们包括抗 TNF-α 制剂、抗黏附分子、抗 IL-12/23、抗 IL-6R 等。我们回顾了超越抗 TNFs 的 UC 治疗的生物治疗的最新进展。

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