Enriched marine oil supplements increase peripheral blood Specialized Pro-resolving Mediators concentrations and reprogram host immune responses: A randomized double-blind placebo-controlled study = Suplementos ricos en aceite marino incrementan las concentraciones de especializados pro-resolutivos mediadores en sangre periférica y reprograman la respuesta inmune del hospedero: Un estudio aleatorio placebo-control

Rationale: Specialized pro-resolving mediators (SPM – lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid (DHA) and docosapentaenoic acid (n-3 DPA). These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood. Objective: Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses. Methods and Results: Healthy volunteers were enrolled in a double blinded, placebo controlled, crossover study and peripheral blood was collected at baseline and 2, 4, 6 and 24h post administration of placebo or one of three doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria, and a decrease in the diurnal activation of leukocytes and platelets, as measured by a decreased adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked shift in transcript levels of immune and metabolic genes 24h post-supplementation when compared with placebo. Conclusions: Together these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood, indicating a role for SPM in mediating the immune directed actions of this supplement