title: Mechanisms behind efficacy of tumor necrosis factor inhibitors in inflammatory bowel diseases.
abstract: Biological treatment with tumor necrosis factor (TNF) inhibitors is successful in the management of inflammatory bowel disease (IBD). All TNF inhibitors antagonize the pro-inflammatory cytokine TNF-α but with varying efficacies in IBD. The variations in efficacy probably are caused by structural differences between the agents that affect their mechanisms of action and pharmacokinetic properties. Several mechanisms have been proposed, such as modulation of the expression of pro-inflammatory mediators and a reduction in the number of activated immune cells. However, it seems that clinical efficacy is the result of a number of different mechanisms and that binding of transmembrane TNF by TNF inhibitors. Knowledge of the mechanisms of action has been obtained mainly through the use of in vitro assays that may differ significantly from the situation in vivo. This review discusses the available data on TNF inhibitors in order to identify mechanisms of importance for their efficacy in IBD. Thus, a better understanding of the mechanistic basis for clinical efficacy can lead to a more rational use of TNF inhibitors in the management of IBD.
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Caroline Meyer
authors.initials: CM
authors.lastname: Olesen
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Electronic address: mehmet.coskun@regionh.dk.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Coskun
authors.affiliation: Department of Gastroenterology, Inserm U954, Nancy University Hospital, Lorraine University, Vandoeuvre, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha
keywords: Crohn's disease; IBD; Inflammatory pathways; TNF inhibitors; Ulcerative colitis