Delayed wound healing due to increased interleukin-10 expression in mice with lymphatic dysfunction

Skin wound healing is an interactive process involving soluble mediators, ECM, resident cells, and infiltrating cells. Little is known about wound healing in the presence of lymphedema. In this study, we investigated wound healing using kCYC(+/-) mice, which demonstrate severe lymphatic dysfunction. Wound healing was delayed significantly in kCYC(+/-) mice when compared with WT mice. In wounded skin of kCYC(+/-) mice, mast cell numbers were increased compared with WT mice, whereas macrophage numbers were decreased. Moreover, IL-10 expression by mast cells was increased, and expression of bFGF, mainly produced by macrophages, was decreased in wounded skin of kCYC(+/-) mice compared with WT mice. We next crossed kCYC(+/-) mice with IL-10(-/-) mice, which were reported to show accelerated wound closure. In kCYC(+/-)IL-10(+/-) mice, time course of wound healing, numbers of macrophages, and IL-10 mRNA expression levels in wounded skin were comparable with WT IL-10(+/-) mice. Similar results were obtained using a different lymphedema model, in which circumferential skin excision was performed on the tails of mice to remove the superficial lymphatics. In summary, these findings suggest that IL-10 plays an important role in delayed wound healing in the setting of lymphatic dysfunction.