Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha Therapy
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. Clin...
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| Main Author: | |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2000-01-01
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| Series: | Canadian Journal of Gastroenterology |
| Online Access: | http://dx.doi.org/10.1155/2000/409396 |
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| Summary: | 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. |
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| ISSN: | 0835-7900 |