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.
Steenfos
H H
HH
Department of Surgery, University of California, San Francisco 94143-0144.
Hunt
T K
TK
Scheuenstuhl
H
H
Goodson
W H
WH
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