Abstract
Tumor necrosis factor (TNF) is a central pro-inflammatory cytokine that regulates the expression of numerous signaling pathways implicated in the progression of the immunological reaction. Unraveling the importance of TNF on the pathogenesis of inflammatory bowel disease (IBD) promoted anti-TNF antibodies as novel therapeutic agents. Initially, the main hypothesis behind the clinical application of anti-TNF antagonists in the clinic was that they exert their effects solely through neutralization of TNF. Anti-TNF antibodies induce and maintain clinical remission in patients with minimal side-effects. However, the cellular and molecular mechanisms of actions of the anti-TNF antibodies remain unknown. Various mechanisms of action have been proposed such as activation of transmembrane TNF mediated reverse signaling, induction of apoptosis, pro-inflammatory cytokine down-regulation, complement dependent cytotoxicity, antibodydependent cell-mediated cytotoxicity, and finally activation of regulatory immune cells via interactions with the Fc receptors. The observed discrepancies in the clinical efficacies as well as the differences in the structure of the various TNF antagonists nourish the investigation for additional modes of function.
Keywords: Antibody-dependent cell-mediated cytotoxicity, complement dependent cytotoxicity, Crohn’s disease, inflammatory bowel disease, macrophages, reverse signaling, tumor necrosis factor, ulcerative colitis.
Current Drug Targets
Title:Anti-TNF Antibodies in Inflammatory Bowel Disease: Do We Finally Know How it Works?
Volume: 14 Issue: 12
Author(s): Angelos Oikonomopoulos, Welmoed K. van Deen and Daniel W. Hommes
Affiliation:
Keywords: Antibody-dependent cell-mediated cytotoxicity, complement dependent cytotoxicity, Crohn’s disease, inflammatory bowel disease, macrophages, reverse signaling, tumor necrosis factor, ulcerative colitis.
Abstract: Tumor necrosis factor (TNF) is a central pro-inflammatory cytokine that regulates the expression of numerous signaling pathways implicated in the progression of the immunological reaction. Unraveling the importance of TNF on the pathogenesis of inflammatory bowel disease (IBD) promoted anti-TNF antibodies as novel therapeutic agents. Initially, the main hypothesis behind the clinical application of anti-TNF antagonists in the clinic was that they exert their effects solely through neutralization of TNF. Anti-TNF antibodies induce and maintain clinical remission in patients with minimal side-effects. However, the cellular and molecular mechanisms of actions of the anti-TNF antibodies remain unknown. Various mechanisms of action have been proposed such as activation of transmembrane TNF mediated reverse signaling, induction of apoptosis, pro-inflammatory cytokine down-regulation, complement dependent cytotoxicity, antibodydependent cell-mediated cytotoxicity, and finally activation of regulatory immune cells via interactions with the Fc receptors. The observed discrepancies in the clinical efficacies as well as the differences in the structure of the various TNF antagonists nourish the investigation for additional modes of function.
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Cite this article as:
Oikonomopoulos Angelos, van Deen K. Welmoed and Hommes W. Daniel, Anti-TNF Antibodies in Inflammatory Bowel Disease: Do We Finally Know How it Works?, Current Drug Targets 2013; 14 (12) . https://dx.doi.org/10.2174/13894501113149990164
DOI https://dx.doi.org/10.2174/13894501113149990164 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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