Lipoxins, resolvins, and the resolution of inflammation

Resolution of acute inflammation is an active process, where endogenous specialized pro-resolving mediators (SPM), derived from polyunsaturated fatty acids via lipoxygenase (LO)-driven biochemical pathways, have pivotal roles in “turning off” pro-inflammatory signals, prompting timely resolution. SPM potent and stereospecific bioactions are of considerable interest in immunopharmacology since unresolved inflammation represents a key pathogenetic mechanism of several widespread diseases. In recent years, biosynthetic routes, chemical structure, and specific G-protein coupled receptors for many members of the SPM genus have been uncovered. This knowledge, that emphasizes the complex pathobiological role of LO in resolution of inflammation, provides previously unforeseen opportunity and strategies for innovative pharmacology for a variety of human pathologies. Here, we provide an overview of biosynthetic pathways, receptors, bioactions and underlying mechanisms as well as of preclinical and clinical evidence of efficacy of the best-studied SPM.