Transforming growth factor beta levels in rat wound chambers.

Exogenous TGF-beta 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-beta levels and cytology. A soft agar assay and a competitive radioreceptor binding assay were used to determine TGF-beta levels. Papanicolau staining and differential cell counts were used to determine cytology. Results were similar using either method for the determination of TGF-beta levels. With the sensitive radioreceptor assay, low TGF-beta 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-beta levels for postwounding Days 6 through 14 were significantly increased over the baseline TGF-beta levels of Days 4 and 5 (P less than 0.05). Day 16 TGF-beta levels were not different from baseline. Cytologic changes were characterized by a liner decrease in total neutrophil count over the exam period and a concurrent linear increase in total lymphocyte and macrophage counts. TGF-beta levels changed in a bell-shaped temporal sequence during healing, apparently unrelated to percentage lymphocyte, macrophage, or neutrophil count. Peak TGF-beta levels occurred during the fibroblast proliferation and collagen synthesis phase of healing. This study presents the first evidence that TGF-beta is present in a healing wound and suggests that it may be an intrinsic mediator of the healing process.