Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases

被引：166

作者：

Billmeier, Ulrike ^{[1
]}

Dieterich, Walburga ^{[1
]}

Neurath, Markus F. ^{[1
]}

Atreya, Raja ^{[1
]}

机构：

[1] Friedrich Alexander Univ Erlangen Nurnberg, Med Clin 1, Ulmenweg 18, D-91054 Erlangen, Germany

来源：

WORLD JOURNAL OF GASTROENTEROLOGY | 2016年 / 22卷 / 42期

关键词：

Mucosal immunology; Lamina propria mononuclear cells; Crohn's disease; Ulcerative colitis; Transmembrane tumor necrosis factor; Apoptosis; PROPRIA MONONUCLEAR-CELLS; CERTOLIZUMAB PEGOL CDP870; TRANSMEMBRANE TNF-ALPHA; CROHNS-DISEASE; ULCERATIVE-COLITIS; INFLIXIMAB THERAPY; T-LYMPHOCYTES; MEMBRANE TNF; IN-VITRO; MONOCLONAL-ANTIBODIES;

D O I：

10.3748/wjg.v22.i42.9300

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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. (C) The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.

引用

页码：9300 / 9313

页数：14

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