title: Tumor necrosis factor-alpha inhibits in vivo collagen synthesis.
abstract: In this study we sought to determine the in vivo role of tumor necrosis factor-alpha (TNF-alpha) at the wound-healing site. In vivo abrogation of endogenous TNF-alpha activity in experimental wounds by administration of anti-murine TNF-alpha 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-alpha into subcutaneously inserted polyvinyl alcohol sponges resulted in an increase in collagen deposition (1594 +/- 117 vs 1014 +/- 49 and 1588 +/- 135 vs 1014 +/- 49 micrograms/100 mg sponge, for TNF-alpha in situ administration at a dose of 0.05 and 0.5 micrograms, 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-alpha administration is a consequence of a nonspecific inflammatory activity that indirectly promotes collagen synthesis. The data also support the hypothesis that endogenous wound TNF-alpha down-regulates collagen synthesis during normal wound healing.
authors.affiliation: Department of Surgery, Sinai Hospital of Baltimore, MD 21215.
authors.forename: M C
authors.initials: MC
authors.lastname: Regan
authors.forename: S J
authors.initials: SJ
authors.lastname: Kirk
authors.forename: M
authors.initials: M
authors.lastname: Hurson
authors.forename: M
authors.initials: M
authors.lastname: Sodeyama
authors.forename: H L
authors.initials: HL
authors.lastname: Wasserkrug
authors.forename: A
authors.initials: A
authors.lastname: Barbul
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis*; D015536:Down-Regulation / Q000502:physiology; D006909:Hydroxyproline / Q000187:drug effects / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology
chemical_list: D000906:Antibodies; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D006909:Hydroxyproline; D007213:Indomethacin