Permissive environment in postnatal wounds induced by adenoviral-mediated overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar formation

Wound Repair Regen. Jan-Feb 2008;16(1):70-9. doi: 10.1111/j.1524-475X.2007.00326.x. Epub 2007 Dec 13.

Abstract

Wound healing in the mid-gestation fetus is scarless with minimal inflammation and a unique extracellular matrix. We have previously documented the relative lack of inflammatory cytokines in this environment. We demonstrate that interleukin (IL)-10 is highly expressed in mid-gestation human fetal skin but is absent in postnatal human skin. We hypothesize that overexpression of IL-10 in postnatal skin may replicate a permissive environment for scarless healing. To study the mechanism underlying this process we performed immunohistochemistry for IL-10 in human mid-gestation fetal and postnatal skin. We also determined if adenoviral-mediated overexpression of IL-10 could allow for scarless wound healing in a murine incisional wound model. Wounds were analyzed at 1-90 days postwounding for effects on scar formation, inflammatory response, and biomechanical properties. Ad-IL-10 reconstitutes a permissive environment for scarless healing as shown by reconstitution of a normal dermal reticular collagen pattern and distribution of dermal elements. Compared with controls, Ad-IL-10 treated wounds showed reduced inflammatory response and no difference in biomechanical parameters. Therefore, overexpression of IL-10 in postnatal wounds results in a permissive environment for scarless wound repair, possibly by replicating a fetal wound environment.

MeSH terms

  • Adenoviridae
  • Animals
  • Biomechanical Phenomena
  • Cicatrix / etiology
  • Cicatrix / immunology*
  • Disease Models, Animal
  • Female
  • Fetus / immunology
  • Genetic Vectors
  • Humans
  • Immunohistochemistry
  • Infant, Newborn
  • Interleukin-10 / biosynthesis*
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy
  • Skin / immunology*
  • Skin Physiological Phenomena / immunology
  • Transgenes
  • Wound Healing / immunology*
  • Wounds and Injuries / immunology*

Substances

  • Interleukin-10