Fetal wound repair results in scar formation in interleukin-10-deficient mice in a syngeneic murine model of scarless fetal wound repair.
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.
Liechty
K W
KW
Children's Institute for Surgical Science at The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, 19104, USA.
Kim
H B
HB
Adzick
N S
NS
Crombleholme
T M
TM
D000818:Animals; D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology*; D005333:Fetus / Q000502:physiology* / Q000601:surgery; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000172:deficiency / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000737:chemistry / Q000473:pathology; D016038:Skin Transplantation; D014185:Transplantation, Isogeneic; D014945:Wound Healing / Q000502:physiology*
D016753:Interleukin-10; D017493:Leukocyte Common Antigens