Differential effect of burn injury on fibroblasts from wounds and normal skin

Background: Although there are well-recognized fluctuations in the systemic concentration of cytokines and growth factors after burn injuries, the effect on wound-healing potential in patients is not well understood. The objective of this study was to characterize the proliferation rate and response of wound and dermal fibroblasts to cytokines in burn patients compared with normal subjects. Methods: Polyvinyl alcohol sponges were implanted subcutaneously in normal subjects and burn patients soon after admission. Sponges were removed for wound fibroblast explantation after 12 days. At the same time, a small piece of skin was excised for dermal fibroblast explantation. Fibroblast proliferation was then quantified after exposure to 10% fetal bovine serum, 1% fetal bovine serum, interleukin-1, transforming growth factor-beta 1, or interferon-alpha 2b. Results: Normal subjects' dermal fibroblasts (n = 7) exposed to 10% fetal bovine serum showed significantly increased proliferation relative to normal subjects' wound fibroblasts (n = 3) (p < 0.0005), burn patients' dermal fibroblasts (n = 5) (p < 0.05), and burn patients' wound fibroblasts (n = 5) (p < 0.0001). Burn patients' dermal fibroblast proliferation was also significantly augmented relative to burn patients' wound fibroblasts (p < 0.005); however, there was no significant difference between the two wound fibroblast types. Proliferation of burn subjects' fibroblasts was significantly enhanced with the addition of interleukin-1 and significantly decreased for dermal fibroblasts with interferon-alpha 2b. A significant elevation of proliferation with transforming growth factor-beta 1 was seen only with burn patients' dermal fibroblasts. Conclusions: The data suggest that systemic mediators markedly alter the proliferation potential of dermal fibroblasts but not of wound fibroblasts. However, the wound environment substantially alters both the proliferation rate and the responsiveness of fibroblasts to cytokines. Thus, the data support the value of using wound fibroblasts during preliminary in vitro experiments to investigate wound-healing modification by cytokine manipulation.