Transforming growth factor β levels in rat wound chambers

Exogenous TGF-β accelerates healing in both normal and doxorubicin-treated rats, but whether it plays an intrinsic role in the natural healing process is unknown. Subcutaneous wound chambers in 16 F344 rats were aspirated from postwounding Day 3 through Day 16 for TGF-β levels and cytology. A soft agar assay and a competitive radioreceptor binding assay were used to determine TGF-β levels. Papanicolau staining and differential cell counts were used to determine cytology. Results were similar using either method for the determination of TGF-β levels. With the sensitive radioreceptor assay, low TGF-ß levels on postwounding Day 4, mean 2.6 ng/ml, rose to a peak mean level of 20.4 ng/ml on Day 7 and fell significantly from peak level to a level of 5.4 ng/ml of Day 16. All TGF-β levels for postwounding Days 6 through 14 were significantly increased over the baseline TGF-β levels of Days 4 and 5 (P < 0.05). Day 16 TGF-β levels were not different from baseline. Cytologic changes were characterized by a linear decrease in total neutrophil count over the exam period and a concurrent linear increase in total lymphocyte and macrophage counts. TGF-β levels changed in a bell-shaped temporal sequence during healing, apparently unrelated to percentage lymphocyte, macrophage, or neutrophil count. Peak TGF-β levels occurred during the fibroblast proliferation and collagen synthesis phase of healing. This study presents the first evidence that TGF-β is present in a healing wound and suggests that it may be an intrinsic mediator of the healing process.