Biology of inflammation in Crohn's disease: mechanisms of action of anti-TNF-a therapy.
Several recent trials of intravenously administered antitumour necrosis factor-alpha (TNF-a) monoclonal antibody have shown dramatic responses among patients with Crohn's disease. These results indicate a primary role for TNF-a in the mediation of altered mucosal immune function in this disease. Clinical responses in patients treated with a single infusion of anti-TNF-a persisted for as long as one year. The prolonged period of clinical benefit shows that the effect of short term TNF-a elimination 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-a-specific augmentation of mucosal Th1 function is the process that is altered by removal of TNF-a and that produces such persistent responses. Understanding how TNF-a modulates mucosal Th1 function may lead to the definition of a key feature of Crohn's disease pathogenesis.
Targan
S R
SR
Cedars-Sinai Medical Center, Los Angeles, CA, USA. stephan.targan@cshs.org
D000818:Animals; D003424:Crohn Disease / Q000188:drug therapy / Q000503:physiopathology*; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000627:therapeutic use
D014409:Tumor Necrosis Factor-alpha