FETAL WOUND REPAIR IN INTERLEUKIN-10 (IL-10) DEFICIENT MICE RESULTS IN SCAR FORMATION

Introduction: Fetal dermal wound healing is characterized by a minimal inflammatory response, restoration of normal dermal architecture, and scarless repair. We previously showed that the production of proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) are diminished in fetal wound repair. IL-10 is an anti-inflammatory cytokine that deactivates macrophages, decreasing production of IL-6 and IL-8. We hypothesized that the diminished IL-6 and IL-8 levels, and minimal inflammation seen in scarless fetal dermal wound repair may be due to increased production of IL-10. To test this hypothesis, we developed a new model of fetal wound repair in normal and IL-10 "knockout" mice. Methods: Fifteen day gestation fetal mouse skin was obtained from either normal C57BL/6 mice or transgenic C57BL/6 mice in which the IL-10 gene has been "knocked out". The skin was grafted to the back of the same strain adult mice. After 1 week the grafts were incisionally wounded and marked with India ink. Grafts were harvested at 1 week and histochemically analyzed for scar using Masson's Trichrome stain. Results: At one week, the normal C57BL/6 fetal skin wounds demonstrated minimal inflammation and the normal dermal reticular collagen pattern at the site of the wound, consistent with scarless repair. In contrast, the wounds in the C57BL/6 IL-10 knockout fetal skin healed with significant inflammation and abnormal collagen deposition at the site of the wound., consistent with scar formation. Conclusion: In a new murine model of fetal wound healing, fetal skin on adult syngeneic mice heals without scar, suggesting scarless repair is intrinsic to fetal skin. The absence of IL-10 in fetal skin results in scar formation. Intrinsic lack of IL-10 in dermal tissue may permit continued amplification of the proinflammatory cytokine cascade, resulting in continued stimulation of fibroblasts in the wound, and abnormal collagen deposition. IL-10 is necessary for scarless wound repair to occur in normal fetal skin.
Kenneth W. Liechty, MD, Heung B. Kim, MD, N. Scott Adzick, MD, FAAP, Timothy M. Crombleholme, MD, FAAP.; The Children's Institute for Surgical Science at The Children's Hospital of Philadelphia, [...]