Selective effects of tumor necrosis factor-alpha on wound healing in rats.
Many growth factors are believed to act simultaneously in wounds. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine released by activated macrophages. In various concentrations it has inflammatory, cytolytic, mitogenic, antitumor, and possibly angiogenic or antiangiogenic effects; therefore it is likely to affect wound healing. With stainless steel wire mesh wound cylinders implanted in rats, we tested topical TNF-alpha in wounds, alone and in combination with platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). The cylinders were injected daily for a total of 12 days, after which we measured the accumulation of protein, DNA, and hydroxyproline in each cylinder. TNF-alpha had little effect by itself; it inhibited the growth-promoting effects of TGF-beta, but it did not influence the effects of PDGF. These results agree with the in vitro studies showing synergism of TNF-alpha and PDGF and antagonism between TGF-beta and TNF-alpha. They also suggest that TGF-beta may have a negligible role in normal healing and emphasize that interaction of growth factors must be understood before appropriate clinical use can be planned.
Department of Surgery, University of California, San Francisco 94143-0144.
H H
HH
Steenfos
T K
TK
Hunt
H
H
Scheuenstuhl
W H
WH
Goodson
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D010982:Platelet-Derived Growth Factor; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D004247:DNA; D006909:Hydroxyproline