PHENOTYPIC DIFFERENCES IN CYTOKINE RESPONSIVENESS OF HYPERTROPHIC SCAR VERSUS NORMAL DERMAL FIBROBLASTS

The alteration of normal dermal fibroblast function that leads to the development of hypertrophic scar after thermal injury is unknown. To d etermine functional differences that might explain this process, fibro blasts were cultured from biopsies of post-thermal injury mature hyper trophic scars and patient-matched normal skin. The mitogenic responses of scar cells to fetal bovine serum, epidermal growth factor (EGF), p latelet-derived growth factor (PDGF), and tumor necrosis factor alpha (TNF alpha) were determined and compared to normal skin cells. Collage n synthetic rate was also compared in the presence and absence of tran sforming growth factor beta(1) (TGF beta(1)). Whereas both scar and no rmal cells responded with increased thymidine uptake to serum and cyto kines, the stimulation to EGF and serum was significantly lower in sca r cells. In contrast, synthesis of collagen, but not of non-collagenou s proteins, was increased in scar relative to normal cells, both basal ly and when stimulated with low doses of TGF beta(1). Additionally, th e fraction of protein synthesized as collagen was significantly higher in scar fibroblasts. These results suggest that fibroblasts from hype rtrophic scars demonstrate stable phenotypic differences in cytokine r esponsiveness in comparison to cells from unaffected skin. The increas ed rate of collagen synthesis and decreased responsiveness to mitogens are consistent with the increased extracellular matrix content and de creased cellularity of hypertrophic scars.