The reinnervation and revascularization of wounds is temporarily altered after treatment with interleukin 10

Denervated wounds fail to heal normally, and hypertrophic scars are abnormally innervated. Wounds can be manipulated with cytokines to reduce subsequent scarring. Wounds treated with the antiscarring cytokine interleukin 10 (IL10) were investigated to assess if the treatment alterered patterns of reinnervation and revascularization as the wounds matured into scars. Thirty CD1 mice underwent intradermal injection of 100 μL phosphate‐buffered saline (PBS) containing 125 ng IL10 or placebo at the margins of 1 cm2 full thickness dorsal skin excisions at the time of wounding and at 24 hours after wounding. Wounds were not dressed. Six IL10‐treated and six control were harvested days 7, 14, 21, 42 and 84 postoperatively. Sections underwent histological scar assessment along with immunohistochemical staining for protein gene product 9.5 (PGP9.5), a pan‐neuronal marker, and the sensory neuropeptides calcitonin gene related peptide (CGRP) and substance P (SP). The endothelial marker von Willebrand factor (VWF) was used to allow co‐localization and quantification of blood vessels. Quantitative analysis was performed on the periphery and center of wounds. Wounds treated with IL10 healed with dermal collagen organized into a pattern more closely resembling normal skin than control wounds. IL10 changed the pattern of CGRP reinnervation during the healing process, but at 84 days, the density levels of all nerve fiber types were similar to controls. Wounds treated with IL10 were more vascular than untreated wounds during healing, but by 84 days, VWF density was that of unwounded skin.