IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation

J Invest Dermatol. 2008 Jul;128(7):1852-60. doi: 10.1038/sj.jid.5701232. Epub 2008 Jan 17.

Abstract

Adult wound healing is characterized by an exuberant inflammatory response and scar formation. In contrast, scarless fetal wound healing has diminished inflammation, a lack of fibroplasia, and restoration of normal architecture. We have previously shown that fetal wounds produce less inflammatory cytokines, and the absence of IL-10, an anti-inflammatory cytokine, results in fetal scar formation. We hypothesized that increased IL-10 would decrease inflammation and create an environment conducive for regenerative healing in the adult. To test this hypothesis, a lentiviral vector expressing IL-10 and green fluorescent protein (GFP) (Lenti-IL-10) or GFP alone (Lenti-GFP) was injected at the wound site 48 hours before wounding. We found that both Lenti-IL-10 and Lenti-GFP were expressed in the wounds at 1 and 3 days post wounding. At 3 days, Lenti-IL-10-treated wounds demonstrated decreased inflammation and decreased quantities of all proinflammatory mediators analyzed with statistically different levels of IL-6, monocyte chemoattractant protein-1, and heat-shock protein 47. At 3 weeks, Lenti-GFP wounds demonstrated scar formation. In contrast, wounds injected with Lenti-IL-10 demonstrated decreased inflammation, a lack of abnormal collagen deposition, and restoration of normal dermal architecture. We conclude that lentivirus-mediated overexpression of IL-10 decreases the inflammatory response to injury, creating an environment conducive for regenerative adult wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cicatrix / physiopathology*
  • Green Fluorescent Proteins / genetics
  • HSP47 Heat-Shock Proteins / physiology
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism*
  • Interleukin-10 / physiology*
  • Lentivirus / genetics
  • Mice
  • Mice, Inbred C57BL
  • Phenotype
  • Regeneration
  • Wound Healing / physiology*

Substances

  • HSP47 Heat-Shock Proteins
  • Inflammation Mediators
  • Interleukin-10
  • Green Fluorescent Proteins