Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators

Abstract

Complete resolution of an acute inflammatory response and its return to homeostasis are essential for healthy tissues. Resolution of acute inflammation is an active process, not just passive termination of inflammation. Novel families of lipid mediators are generated in inflammatory exudates during the resolution phase and they can promote and/or accelerate resolution. These mediators include the lipoxins, and the resolvins and (neuro)protectins, which are derived from the omega-3 essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The pro-resolution lipid mediators are agonists of resolution, with multiple mechanisms of action at the tissue level: they 'stop' neutrophil and eosinophil infiltration; stimulate non-phlogistic recruitment of monocytes; enhance macrophage phagocytosis of apoptotic neutrophils; increase the exit of phagocytes from the inflammatory site to the lymphatics; and stimulate mucosal antimicrobial defence. Pro-resolution and anti-inflammation are not equivalent; pro-resolution programmes stimulate and activate endogenous pathways to terminate inflammation. Pro-resolution lipid mediators exert their protective activity at multiple levels in a range of cell types and in complex disease systems. Pro-resolution lipid mediators promote resolution of inflammation in oral, lung, ocular, kidney, neural and gastrointestinal inflammatory diseases, as well as in ischaemia–reperfusion injury and angiogenesis.