Pro-resolving lipid mediators attenuate lung inflammation (P5080)

Abstract

Abstract Introduction: Cigarette smoking is the major world-wide cause of COPD and other inflammatory diseases. COPD persists after smoking cessation, suggesting that this may be a failure to resolve inflammation. Resolution of inflammation is an active process regulated by small lipid mediators derived mainly from omega-3 polyunsaturated fatty acids, including the resolvins, and others. We hypothesized that resolvin D1 (RvD1) would have anti-inflammatory and pro-resolving effects in cigarette smoke-induced lung inflammation. Methods: Primary human lung cells (e.g. fibroblasts, etc) were treated with cigarette smoke extract and RvD1 in vitro, and production of pro-inflammatory mediators was determined. Mice were exposed to dilute mainstream cigarette smoke and treated with RvD1 either concurrently with smoke or after smoking cessation. The effect on lung inflammation was assessed. Results: RvD1 suppressed production of pro-inflammatory mediators by human cells. Treatment of mice with RvD1 concurrently with cigarette smoke exposure significantly reduced neutrophilic lung inflammation and production of pro-inflammatory cytokines. RvD1 promoted differentiation of alternatively activated (M2) macrophages. RvD1 also accelerated the resolution of lung inflammation when given after the final smoke exposure. Conclusions: RvD1 has potent pro-resolving effects in cells and mice exposed to cigarette smoke. Resolvins may be a novel therapeutic approach to resolve lung injury and disease.