Obesity and
type 2 diabetes are emerging global epidemics associated with chronic, low-grade
inflammation. A characteristic feature of
type 2 diabetes is delayed wound healing, which increases the risk of
recurrent infections, tissue
necrosis, and limb
amputation. In health,
inflammation is actively resolved by endogenous mediators, such as the resolvins. D-series resolvins are generated from
docosahexaenoic acid (DHA) and promote macrophage-mediated clearance of microbes and apoptotic cells. However, it is not clear how
type 2 diabetes affects the resolution of
inflammation. Here, we report that resolution of acute
peritonitis is delayed in obese diabetic (db/db) mice. Altered resolution was associated with decreased apoptotic cell and
Fc receptor-mediated macrophage clearance. Treatment with
resolvin D1 (RvD1) enhanced resolution of
peritonitis, decreased accumulation of apoptotic thymocytes in diabetic mice, and stimulated diabetic macrophage phagocytosis. Conversion of DHA to monohydroxydocosanoids, markers of resolvin biosynthesis, was attenuated in diabetic
wounds, and local application of RvD1 accelerated
wound closure and decreased accumulation of apoptotic cells and macrophages in the
wounds. These findings support the notion that diabetes impairs resolution of wound healing and demonstrate that stimulating resolution with proresolving
lipid mediators could be a novel approach to treating chronic, nonhealing
wounds in patients with diabetes.