IL-10 Overexpression Decreases Inflammatory Mediators and Promotes Regenerative Healing in an Adult Model of Scar Formation

• Published in: Journal of investigative dermatology Vol. 128; no. 7; pp. 1852 - 1860
• Main Authors: Peranteau, William H., Zhang, Liping, Muvarak, Nidal, Badillo, Andrea T., Radu, Antoneta, Zoltick, Philip W., Liechty, Kenneth W.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.07.2008; Nature Publishing; Elsevier Limited
• Subjects: Animals; Biological and medical sciences; Cicatrix - physiopathology; Dermatology; Green Fluorescent Proteins - genetics; HSP47 Heat-Shock Proteins - physiology; Inflammation - prevention & control; Inflammation Mediators - metabolism; Interleukin-10 - physiology; Lentivirus - genetics; Medical sciences; Mice; Mice, Inbred C57BL; Phenotype; Regeneration; Wound Healing - physiology; Human; Dermatology; Scar; Gene overexpression; Inflammation; Decrease; Healing agent; Interleukin 10; Adult; Models; Mediator; Cicatrization; Formation
• ISSN: 0022-202X; 1523-1747; 1523-1747
• DOI: 10.1038/sj.jid.5701232

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 48hours 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.