Review article: targeting TNF alpha as a key cytokine in the inflammatory processes of Crohn's disease--the mechanisms of action of infliximab.
Crohn's disease is a chronic, debilitating gastrointestinal disorder in which a variety of cellular processes and pro-inflammatory mediators influence the pathogenesis of the disease. Although the potential roles and functions of the pro-inflammatory mediators continue to be debated, several mediators, specifically tumour necrosis factor-alpha, have been clearly identified as having a pivotal role in the inflammation of the bowel mucosa of these patients. Therapies specifically focusing on the inflammatory process underlying Crohn's disease have the potential for providing disease modification and prolonged remission. Infliximab, an antitumour necrosis factor-alpha monoclonal antibody, has been demonstrated to neutralize tumour necrosis factor-alpha and restore and reset the immunological dysbalance of the inflamed mucosa. Preliminary studies with infliximab suggested that treatment resulted in a rapid and almost complete inhibition of multiple inflammatory pathways. In clinical studies of infliximab, patients with Crohn's disease achieved rapid reduction in clinical signs and symptoms, substantiated by both endoscopic and microscopic evaluation.
van Deventer
S J
SJ
Afdeling Maag-Darm-Leverziekten, Academisch Medisch Centrum, Amsterdam, The Netherlands.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab