title: Apoptosis as a therapeutic tool in IBD?
abstract: Defective apoptosis of mucosal cell populations seems to be a relevant pathogenetic mechanism in inflammatory bowel disease (IBD). It has been suggested that the induction of apoptosis in various effector cells may be a relevant therapeutic mechanism in IBD. Indeed, it was shown that different drugs used for treatment of IBD have the capacity to induce apoptosis in T cells or monocytes in vitro and in vivo. However, it remains unclear whether these observations are related to clinical efficacy of these agents. TNF-alpha is one of the most relevant proinflammatory mediators in IBD and anti-TNF treatment has been shown to be of particular benefit for patients with IBD. It could subsequently be shown that various anti-TNF-alpha agents, such as infliximab and adalimumab, can induce apoptosis in activated monocytes and lymphocytes in vitro and in vivo. This mechanism requires reverse signaling via transmembranous TNF, thereby eliciting a signal transduction cascade that results in programmed cell death. Although other mechanisms might also contribute to the clinical effect of anti-TNF-alpha, current data suggest that apoptosis is a relevant mechanism that is associated with clinical efficacy of anti-TNF agents. Induction of apoptosis in activated monocytes or T cells may be regarded as therapeutic tool not only for anti-TNF agents, but also for other drugs used in IBD. Future strategies should focus on identification of mechanisms that prevent apoptosis in the mucosa of patients with IBD and in targeting apoptotic pathways as a therapeutic strategy in IBD.
authors.affiliation: Department of Medicine B, University of Münster, Albert-Schweitzer-Strasse 33, D-48129 Münster, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lügering
authors.forename: Pia
authors.initials: P
authors.lastname: Lebiedz
authors.forename: Stefan
authors.initials: S
authors.lastname: Koch
authors.forename: Torsten
authors.initials: T
authors.lastname: Kucharzik
mesh_terms: D017209:Apoptosis; D003424:Crohn Disease / Q000503:physiopathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal; D007249:Inflammation / Q000503:physiopathology; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases