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

WH Peranteau, L Zhang, N Muvarak, AT Badillo… - Journal of Investigative …, 2008 - Elsevier
WH Peranteau, L Zhang, N Muvarak, AT Badillo, A Radu, PW Zoltick, KW Liechty
Journal of Investigative Dermatology, 2008Elsevier
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 …
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.
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