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从免疫原性机制到炎症性肠病的新型治疗方法

From immunogenic mechanisms to novel therapeutic approaches in inflammatory bowel disease.

作者信息

Holtmann Martin H, Neurath Markus F

机构信息

1st Department of Medicine, Johannes-Gutenberg-University, Mainz, Germany.

出版信息

Adv Exp Med Biol. 2006;579:227-42. doi: 10.1007/0-387-33778-4_15.

Abstract

Crohn's disease (CD) and ulcerative colitis (UC) are the two most common forms of chronic inflammatory bowel disease (IBD). The etiology of IBD is still unclear and should be considered as multi-factorial according to recent studies. Genetic factors seem to play a pathogenetic role as well as environmental, infectious and immulogical factors. Substantial progress, however, has been made in the understanding of the pathogenesis of IBD during the past years persuing the view, that IBD could result from disturbances of the intestinal barrier and a pathologic activation of the intestinal immune response towards luminal, bacterial antigens. This paradigm has led to the identification of key players of the intestinal immune system, which represent promising targets for novel therapeutic approaches. The objective of this chapter is to provide an overview over recent advances in the elucidation of the intestinal immune system in IBD and novel therapeutic approaches that have been derived from these results. Molecular biological techniques have revealed, that many of the established conventional antiinflammatory drugs such as salicylic acids, steroids or immunuosuppressants act at the same molecules that are the target for modern biologicals, i.e., the cytokine TNF or the transcription factor NFkappaB. This chapter, however, focusses on novel experimental approaches such as recombinant antiinflammatory cytokines, neutralizing antibodies or antisense oligonucleotides.

摘要

克罗恩病(CD)和溃疡性结肠炎(UC)是慢性炎症性肠病(IBD)最常见的两种形式。IBD的病因仍不清楚,根据最近的研究应被视为多因素的。遗传因素以及环境、感染和免疫因素似乎都起着致病作用。然而,在过去几年中,在理解IBD发病机制方面取得了重大进展,即认为IBD可能是由肠道屏障紊乱以及肠道对腔内细菌抗原的免疫反应的病理性激活所致。这种范式已导致识别出肠道免疫系统的关键参与者,它们是新型治疗方法的有希望的靶点。本章的目的是概述IBD肠道免疫系统阐明方面的最新进展以及从这些结果中衍生出的新型治疗方法。分子生物学技术已经揭示,许多已确立的传统抗炎药物,如水杨酸、类固醇或免疫抑制剂,作用于与现代生物制剂相同的分子靶点,即细胞因子TNF或转录因子NFκB。然而,本章重点关注新型实验方法,如重组抗炎细胞因子、中和抗体或反义寡核苷酸。

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