Inhibition of tumour necrosis factor-α and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation
Trebble T., Arden NK., Stroud MA., Wootton SA., Burdge GC., Miles EA., Ballinger AB., Thompson RL., Calder PC.
<jats:p>Increased dietary consumption of the<jats:italic>n</jats:italic>-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (20:5<jats:italic>n</jats:italic>-3; EPA) and docosahexaenoic acid (22:6<jats:italic>n</jats:italic>-6; DHA) is associated with their incorporation into circulating phospholipid and increased production of lipid peroxide metabolites. The relationship between peripheral blood mononuclear cell (PBMC) function,<jats:italic>n</jats:italic>-3 PUFA intake and antioxidant co-supplementation is poorly defined. We therefore investigated tumour necrosis factor (TNF)-α and interleukin (IL) 6 production by PBMC and phospholipid fatty acid composition in plasma and erythrocytes of healthy male subjects (<jats:italic>n</jats:italic>16) receiving supplemental intakes of 0·3, 1·0 and 2·0 g EPA+DHA/d, as consecutive 4-week courses. All subjects were randomised in a double-blind manner to receive a concurrent antioxidant supplement (200 μg Se, 3 mg Mn, 30 mg D-α-tocopheryl succinate, 90 mg ascorbic acid, 450 μg vitamin A (β-carotene and retinol)) or placebo. There was a positive dose-dependent relationship between dietary<jats:italic>n</jats:italic>-3 PUFA intake and EPA and DHA incorporation into plasma phosphatidylcholine and erythrocyte phosphatidylethanolamine, with a tendency towards a plateau at higher levels of intake. Production of TNF-α and IL-6 by PBMC decreased with increasing<jats:italic>n</jats:italic>-3 PUFA intake but tended towards a ‘U-shaped’ dose response. Both responses appeared to be augmented by antioxidant co-supplementation at intermediate supplementary<jats:italic>n</jats:italic>-3 PUFA intakes. Thus, increased dietary<jats:italic>n</jats:italic>-3 PUFA consumption resulted in defined but contrasting patterns of modulation of phospholipid fatty acid composition and PBMC function, which were further influenced by antioxidant intake.</jats:p>