Calder Philip C
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, IDS Building, MP887 Southampton General Hospital, Tremona Road, Southampton SO16 6YD, U.K.
NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton SO16 6YD, U.K.
Biochem Soc Trans. 2017 Oct 15;45(5):1105-1115. doi: 10.1042/BST20160474. Epub 2017 Sep 12.
Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are capable of partly inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid and production of pro-inflammatory cytokines. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB so reducing expression of inflammatory genes and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ. Animal experiments demonstrate benefit from EPA and DHA in a range of models of inflammatory conditions. Human trials demonstrate benefit of oral n-3 fatty acids in rheumatoid arthritis and in stabilizing advanced atherosclerotic plaques. Intravenous n-3 fatty acids may have benefits in critically ill patients through reduced inflammation. The anti-inflammatory and inflammation resolving actions of EPA, DHA and their derivatives are of clinical relevance.
不适当、过度或不受控制的炎症会引发一系列人类疾病。炎症涉及多种细胞类型、化学介质及相互作用。本文将描述ω-6（n-6）和ω-3（n-3）脂肪酸的营养和代谢方面，并解释这些脂肪酸家族中的生物活性成分在炎症过程中的作用。二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）是在油性鱼类和鱼油补充剂中发现的n-3脂肪酸。这些脂肪酸能够部分抑制炎症反应中的许多方面, 包括白细胞趋化性、黏附分子表达以及白细胞与内皮细胞的黏附相互作用、由n-6脂肪酸花生四烯酸产生类二十烷酸如前列腺素和白三烯以及促炎细胞因子的产生。此外，EPA产生类二十烷酸的生物活性通常低于花生四烯酸产生的类二十烷酸，并且EPA和DHA会产生称为消退素、保护素和促消退介质的抗炎和促炎症消退介质。EPA和DHA抗炎作用的潜在机制包括改变细胞膜磷脂脂肪酸组成、破坏脂筏、抑制促炎转录因子核因子κB的激活从而减少炎症基因的表达以及激活抗炎转录因子过氧化物酶体增殖物激活受体γ。动物实验表明，EPA和DHA在一系列炎症性疾病模型中具有益处作用。人体试验表明，口服n-3脂肪酸对类风湿性关节炎和稳定晚期动脉粥样硬化斑块有益。静脉注射n-3脂肪酸可能通过减轻炎症对重症患者有益。EPA、DHA及其衍生物的抗炎和促炎症消退作用具有临床意义。
