02.01 The Role of Endogenously Expressed IL-10 in Wound Closure and Tissue Repair

B. W. Padon1, 2, T. J. Prajapati1, 2, F. M. Faruk1, 2, W. D. Short1, 2, O. Olutoye1, 2, H. Li1, 2, M. Rae1, T. Lu1, S. G. Keswani1, 2, S. Balaji1, 2  1Baylor College of Medicine, Pediatric General Surgery, Houston, TX, USA 2Texas Children’s Hospital, Pediatric General Surgery, Houston, TX, USA


Our lab has shown a significant role for IL-10 overexpression in regulating inflammation and extracellular matrix (ECM) production, thereby attenuating fibrosis in skin wounds. However, the role of IL-10 in wound closure is unclear, as previous studies in murine wounds, not controlled for contraction and moist wound environment, have shown increased rates of wound closure in IL-10-/- mice. The objective of this study is to determine the role of endogenous IL-10 on wound closure when controlling for contraction and a moist wound environment.


Full thickness 6mm wounds were made in C57B6/J WT and IL-10-/- mice and controlled for contraction using a silicone stent. A moist wound environment was provided by Tegaderm dressing. Wounds were serially photographed at 3, 5 and 7d, harvested at 7d and 30d post wounding, then examined for epithelial gap, granulation tissue, scar area(H&E), myofibroblasts(aSMA), and leukocyte(CD45) and macrophage content(F4/80). Data is mean+-SD, n=8-10 wounds/group/time; p-value by ANOVA.


In contrast to prior reports, unstented IL-10-/- wounds maintained in a moist wound environment showed no significant difference in epithelial gap at d7, but had an increase in granulation tissue (IL-10-/- 1.4+-0.6 vs WT 0.8+-0.4 mm2, p<0.01) compared to WT. Unstented IL-10-/- wounds exhibited a heightened inflammatory response, with an elevated % of CD45+ (IL-10-/- 28.9%+-14.1 vs WT 6.0+-2.7, p<.01) and F4/80+ (IL-10-/- 53.7%+-1.2 vs WT 28.3+-0.5, p<.01) cells/high power field(HPF). Upon stenting the wounds, no difference in epithelial gap and granulation tissue was seen. The increase in % of F4/80+ cells/HPF (IL-10-/- 21.3%+-3.6 vs WT 22.4+-5.4, p<.05) persisted in stented wounds. There was a marked increase in the % of CD45+ cells/HPF (IL-10-/-22.4%+-1.5 vs WT 13.6%+-1.7, p=ns) as well. aSMA showed abundant expression at the wound margins in all wounds, but stented wounds had more aSMA present in the granulation tissue compared to unstented wounds. IL-10-/- wounds had more aSMA staining in the wound bed than WT. However, analysis of the % of aSMA + cells/HPF showed no significant difference in the stented and unstented wounds. At d30, wounds in IL-10-/- mice had significantly larger scar area as compared WT in stented (IL-10-/- 0.24+-0.02 vs WT 0.17+-0.06 mm2, p<.05) and unstented (IL-10-/- 0.18+-0.01 vs WT 0.13+-0.03 mm2, p<.05) groups.


Our data showed endogenous IL-10 does not delay normal healing of skin wounds when controlled for contraction and moist environment. However, the loss of IL-10 leads to increased inflammation and fibrosis. This data signifies a previously unrecognized role for endogenously expressed IL-10 contributing to the tissue repair response.