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Canadian Journal of Gastroenterology
Volume 14 (2000), Suppl C, Pages 13C-16C

Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha Therapy

Stephan R Targan

Cedars-Sinai Medical Center, Los Angeles, California, USA

Copyright © 2000 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Several recent trials of intravenously administered antitumour necrosis factor-alpha (TNF-α) monoclonal antibody have shown dramatic responses among patients with Crohn’s disease. These results indicate a primary role for TNF-αin the mediation of altered mucosal immune function in this disease. Clinical responses in patients treated with a single infusion of anti-TNF-αpersisted for as long as one year. The prolonged period of clinical benefit shows that the effect of short term TNF-αelimination remains long after the monoclonal antibody has cleared the body. Corresponding in vitro investigation has shown that T helper 1 (Th1) -mediated cytokine production of interferon-gamma is downregulated in the involved mucosa to a level consistent with that seen in uninflamed mucosa. These results suggest that TNF-α-specific augmentation of mucosal Th1 function is the process that is altered by removal of TNF-αand that produces such persistent responses. Understanding how TNF-αmodulates mucosal Th1 function may lead to the definition of a key feature of Crohn’s disease pathogenesis.