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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| Format: | Article |
| Language: | English |
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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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| _version_ | 1832561765668356096 |
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| author | Stephan R Targan |
| author_facet | Stephan R Targan |
| author_sort | Stephan R Targan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-57b848ac467149d9907e218212b3c46f |
| institution | Kabale University |
| issn | 0835-7900 |
| language | English |
| publishDate | 2000-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Gastroenterology |
| spelling | doaj-art-57b848ac467149d9907e218212b3c46f2025-02-03T01:24:16ZengWileyCanadian Journal of Gastroenterology0835-79002000-01-0114Suppl C13C16C10.1155/2000/409396Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha TherapyStephan R Targan0Cedars-Sinai Medical Center, Los Angeles, California, USASeveral 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.http://dx.doi.org/10.1155/2000/409396 |
| spellingShingle | Stephan R Targan Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha Therapy Canadian Journal of Gastroenterology |
| title | Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha Therapy |
| title_full | Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha Therapy |
| title_fullStr | Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha Therapy |
| title_full_unstemmed | Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha Therapy |
| title_short | Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha Therapy |
| title_sort | biology of inflammation in crohn s disease mechanisms of action of anti tnf αalpha therapy |
| url | http://dx.doi.org/10.1155/2000/409396 |
| work_keys_str_mv | AT stephanrtargan biologyofinflammationincrohnsdiseasemechanismsofactionofantitnfaalphatherapy |