title: Redeeming an old foe: protective as well as pathophysiological roles for tumor necrosis factor in inflammatory bowel disease.
abstract: Tumor necrosis factor (TNF) and its receptors TNFR1 and TNFR2 are major therapeutic targets for inflammatory bowel disease. Research advances have demonstrated that TNF produces pleiotropic responses in the gastrointestinal (GI) tract. Although in excess TNF can contribute to GI pathology, TNF is also a critical protective factor to promote GI homeostasis following injury and inflammation. Genetic studies using candidate and genome-wide association study approaches have identified variants in TNF or its receptors that are associated with Crohn's disease or ulcerative colitis in multiple populations, although the basis for these associations remains unclear. This review considers the efficacy and mechanism of anti-TNF therapies for inflammatory bowel disease to reconcile the many disparate aspects of TNF research and to consider the potential protective effects of TNF signaling in GI health.
authors.affiliation: Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California; Department of Pediatrics, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, California; and.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Dubé
authors.affiliation: Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California; Department of Pediatrics, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, California; and.
authors.forename: Shivesh
authors.initials: S
authors.lastname: Punit
authors.affiliation: Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California; Department of Pediatrics, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, California; and Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, Los Angeles, California dbpolk@chla.usc.edu.
authors.forename: D Brent
authors.initials: DB
authors.lastname: Polk
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D041981:Gastrointestinal Tract / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D018124:Receptors, Tumor Necrosis Factor; D048069:Tumor Necrosis Factors
keywords: inflammatory bowel disease; tumor necrosis factor; tumor necrosis factor receptor 1; tumor necrosis factor receptor 2