title: Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases.
abstract: 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-actionin vivoandin 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.
authors.affiliation: Ulrike Billmeier, Walburga Dieterich, Markus F Neurath, Raja Atreya, Medical Clinic 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Billmeier
authors.affiliation: Ulrike Billmeier, Walburga Dieterich, Markus F Neurath, Raja Atreya, Medical Clinic 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Walburga
authors.initials: W
authors.lastname: Dieterich
authors.affiliation: Ulrike Billmeier, Walburga Dieterich, Markus F Neurath, Raja Atreya, Medical Clinic 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.affiliation: Ulrike Billmeier, Walburga Dieterich, Markus F Neurath, Raja Atreya, Medical Clinic 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Raja
authors.initials: R
authors.lastname: Atreya
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000906:Antibodies / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D005765:Gastrointestinal Agents; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha
keywords: Apoptosis; Crohn’s disease; Lamina propria mononuclear cells; Mucosal immunology; Transmembrane tumor necrosis factor; Ulcerative colitis