K W Liechty1, H B Kim, N S Adzick, T M Crombleholme. 1. Children's Institute for Surgical Science at The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, 19104, USA.
Abstract
BACKGROUND: Fetal dermal wound healing is characterized by minimal inflammation, restoration of normal dermal architecture, and scarless repair. The authors have shown that proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) are diminished during fetal wound repair. Interleukin-10 (IL-10) is an antiinflammatory cytokine that decreases production of IL-6 and IL-8. The authors hypothesized that diminished IL-6 and IL-8 and minimal inflammation may be caused by IL-10. METHODS: To test this hypothesis, the authors developed a new syngeneic murine model of fetal wound repair in which 15-day-gestation skin from either normal C57BL/6 or transgenic C57BL/6 IL-10 knockout mice was grafted to the back of the same strain adult mice. The grafts were incisionally wounded after 5 days, harvested at 1 week, and analyzed for inflammatory response and scar formation. RESULTS: Wounds in normal fetal skin grafts showed minimal inflammation and normal dermal reticular collagen pattern at the site of the wound, consistent with scarless repair. In contrast, wounds in IL-10 knockout fetal skin grafts showed significant inflammation and scar formation. CONCLUSIONS: Fetal skin grafts on adult syngeneic mice heal without inflammation or scar formation. The absence of IL-10 in fetal skin results in scar formation. Intrinsic lack of IL-10 may result in continued amplification of the inflammatory cytokine cascade, continued stimulation of fibroblasts, and abnormal collagen deposition. IL-10 is necessary for scarless wound repair to occur.
BACKGROUND: Fetal dermal wound healing is characterized by minimal inflammation, restoration of normal dermal architecture, and scarless repair. The authors have shown that proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) are diminished during fetal wound repair. Interleukin-10 (IL-10) is an antiinflammatory cytokine that decreases production of IL-6 and IL-8. The authors hypothesized that diminished IL-6 and IL-8 and minimal inflammation may be caused by IL-10. METHODS: To test this hypothesis, the authors developed a new syngeneic murine model of fetal wound repair in which 15-day-gestation skin from either normal C57BL/6 or transgenic C57BL/6 IL-10 knockout mice was grafted to the back of the same strain adult mice. The grafts were incisionally wounded after 5 days, harvested at 1 week, and analyzed for inflammatory response and scar formation. RESULTS: Wounds in normal fetal skin grafts showed minimal inflammation and normal dermal reticular collagen pattern at the site of the wound, consistent with scarless repair. In contrast, wounds in IL-10 knockout fetal skin grafts showed significant inflammation and scar formation. CONCLUSIONS: Fetal skin grafts on adult syngeneic mice heal without inflammation or scar formation. The absence of IL-10 in fetal skin results in scar formation. Intrinsic lack of IL-10 may result in continued amplification of the inflammatory cytokine cascade, continued stimulation of fibroblasts, and abnormal collagen deposition. IL-10 is necessary for scarless wound repair to occur.
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