A major advance in the use of growth factors to enhance wound healing.

Editorial The article in this issue of The Journal by Beck, Amento, and colleagues (1) is a landmark in its conceptual approach to the use of peptide growth factors for experimental wound healing and presages important clinical applications in the future. As background, it has been known for more than 10 years that direct application of peptide growth factors (cytokines) to an experimental wound will accelerate healing, and the agent used in the present study, TGF-f3, was one of the first cytokines shown to be effective for this purpose (2-4). The present article is conceptually unique in that the authors have shown that direct application of a peptide growth factor to a wound is not necessary to enhance healing; systemic administration can be equally effective. The experimental design has been to use rats whose intrinsic capacity to heal wounds is defective, either as a result of old age or from treatment with a glucocorticoid, and to make standard dorsal inci-sional wounds. These rats have been treated intravenously with a single dose of TGF-f1, while untreated wounded rats have served as controls. Significantly, TGF-f was effective in enhancing healing whether it was given at the time ofwounding, 4 h after wounding, or, most surprisingly, even 24 h before wounding; this effect was measured either by increased tensile strength ofthe treated wound 1 wk later, or by increased deposi-tion of extracellular matrix, particularly collagen. What are the mechanisms whereby systemic administration of TGF-f3, given before the creation ofa wound, can accelerate its subsequent healing? Clearly this is a result that could be of major clinical significance, and further understanding of its mechanism is therefore needed. To begin, TGF-3 is the pro-totypical multifunctional cytokine. Its receptors, actions, and effects are germane to almost every cell in the body involved in tissue injury and repair. Thus, a-granules of platelets are a highly concentrated source ofTGF-f3, while macrophages both react to TGF-,3 with a strong chemotactic response (concentrations as low as 10-15 M are effective) and also secrete several other cytokines when exposed to TGF-,3. TGF-,3 is also a key regulatory molecule in the control ofthe activity of fibroblasts. TGF-f is strongly chemotactic for these cells and regulates their production of almost every known molecule ofthe extra-cellular matrix, including collagen, fibronectin, tenascin, as well as the integrins that are the receptors for these molecules. Furthermore, TGF-f3 blocks the destruction of newly synthesized extracellular matrix by …