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 and n-3 docosapentaenoic acid. 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, 2, 4, 6, and 24 hours post administration of placebo or one of 3 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 reduction in adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24 hours 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 cells, indicating a role for SPM in mediating the immune-directed actions of this supplement. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT03347006.

中文翻译：

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富含海洋油的补品可以增加外周血的专业亲和性调和药浓度，并重新设定宿主的免疫反应：一项随机双盲安慰剂对照研究。

原理专门的促分解介体（SPM-脂类毒素，resolvins，protectin和maresins）是通过必需脂肪酸（包括omega-3脂肪酸二十二碳六烯酸和n-3二十碳五烯酸）的酶促转化产生的。这些介体发挥有效的白细胞定向作用并控制血管炎症。给动物和人类补充必需脂肪酸，特别是omega-3脂肪酸，可起到减少血管和全身炎症的保护作用。值得注意的是，这些补充剂在发挥其保护作用时所激活的机制仍然知之甚少。目的鉴于必需脂肪酸是SPM生物合成中的前体，本研究的目的是建立补充与周围SPM浓度之间的关系。我们还研究了血浆SPM浓度变化与外周血血小板和白细胞反应之间的关系。方法和结果健康志愿者参加了一项双盲，安慰剂对照，交叉研究，并在服用安慰剂或三剂丰富海洋药物之一，给药后第2、4、6和24小时基线采集外周血油补充剂。使用脂质介体谱法评估血浆SPM浓度表明外周血SPM浓度随时间和剂量而增加。补充还导致对外周血细胞反应的调节。在这里，我们发现细菌的嗜中性粒细胞和单核细胞吞噬作用呈剂量依赖性增加，白细胞和血小板的昼夜活化减少，通过粘附分子表达的减少来测量。此外，与安慰剂相比，补充后24小时的外周血细胞转录组分析显示免疫和代谢基因的转录水平有明显变化。结论综上所述，这些发现表明，添加丰富的海洋油会导致外周血SPM浓度增加并重编程外周血细胞，这表明SPM在介导该补品的免疫定向作用中发挥了作用。临床试验注册网址：http://www.clinicaltrials.gov。唯一标识符：NCT03347006。结论综上所述，这些发现表明，添加丰富的海洋油会导致外周血SPM浓度增加并重编程外周血细胞，这表明SPM在介导该补品的免疫定向作用中发挥了作用。临床试验注册网址：http://www.clinicaltrials.gov。唯一标识符：NCT03347006。结论综上所述，这些发现表明，添加丰富的海洋油会导致外周血SPM浓度增加并重编程外周血细胞，这表明SPM在介导该补品的免疫定向作用中发挥了作用。临床试验注册网址：http://www.clinicaltrials.gov。唯一标识符：NCT03347006。