Original communication| Volume 113, ISSUE 2, P173-177, February 1993

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Tumor necrosis factor-α inhibits in vivo collagen synthesis

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      In this study we sought to determine the in vivo role of tumor necrosis factor-α (TNF-α) at the wound-healing site. In vivo abrogation of endogenous TNF-α activity in experimental wounds by administration of anti-murine TNF-α rabbit serum resulted in a significant 77.5% increase in wound collagen deposition, as assessed by wound sponge granuloma hydroxyproline content. Administration of pharmacologic doses of recombinant murine TNF-α into subcutaneously inserted polyvinyl alcohol sponges resulted in an increase in collagen deposition (1594 ± 777 vs 1014 ± 49 and 1588 ± 135 vs 1014 ± 49 μg/100 mg sponge, for TNF-α in situ administration at a dose of 0.05 and 0.5 μg, respectively). This effect could be abolished by the simultaneous systemic treatment of the animals with the antiinflammatory drug indomethacin. The data suggest that the enhanced collagen deposition after TNF-α administration is a consequence of a nonspecific inflammatory activity that indirectly promotes collagen synthesis. The data also support the hypothesis that endogenous wound TNF-α down-regulates collagen synthesis during normal wound healing.
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