Resolvins attenuate cigarette smoke-induced lung inflammation and injury (120.31)

Abstract

Abstract Cigarette smoke induced chronic obstructive pulmonary disease (COPD) is a major global health issue with an increasing incidence worldwide. Inflammation plays an integral role in the development of chronic lung diseases such as COPD. Unresolved inflammatory responses in COPD can lead to tissue damage and dysfunction. Current therapies for COPD only treat symptoms and do not alter the course of the disease. Resolution of inflammatory responses was once believed to be passive, however, recent studies have shown that resolution is a biosynthetically active process involving endogenous pro-resolving lipid mediators, derived from omega-3 and omega-6 polyunsaturated fatty acids that control and limit inflammatory responses. Resolvin D1 (RvD1) is an endogenous lipid mediator that displays potent anti-inflammatory and pro-resolving actions without being immunosuppressive. We hypothesized that RvD1 would be beneficial in a smoke-induced lung injury model. Cigarette smoke-exposed mice treated with RvD1 exhibited a greater than 50% reduction in neutrophil accumulation in the lung lavage fluid, coupled with significant reductions in the neutrophil chemoattractants KC and MIP-2. IL-6 and IL-1β were also reduced. RvD1 treated mice also had enhanced phagocytosis of apoptotic neutrophils by macrophages. Interestingly, RvD1 drives polarization of alternatively activated macrophages (M2) that may facilitate resolution of inflammation and attenuate tissue damage.