Volume 90, Issue 2, August (2003), pp. 405-413 © The Author 2003
doi:10.1079/BJN2003892

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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

Timothy Trebble¹, Nigel K. Arden², Mike A. Stroud¹, Stephen A. Wootton¹, Graham C. Burdge¹, Elizabeth A. Miles¹, Anne B. Ballinger³, Rachel L. Thompson¹, Philip C. Calder^1
1The Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton, SO16 6YD, , UK
²MRC Environmental Epidemiology Unit, University of Southampton, Tremona Road, Southampton General Hospital, Southampton, SO16 6YD, , UK
³Department of Adult and Paediatric Gastroenterology, Barts and the London, Queen Mary's School of Medicine and Dentistry, University of London, London, E1 2AD, , UK

 (Received 4 July 2002–Revised 27 February 2003–Accepted 13 March 2003)

Increased dietary consumption of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (20 : 5n-3; EPA) and docosahexaenoic acid (22 : 6n-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, n-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 (n 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 n-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 n-3 PUFA intake but tended towards a ‘U-shaped’ dose response. Both responses appeared to be augmented by antioxidant co-supplementation at intermediate supplementary n-3 PUFA intakes. Thus, increased dietary n-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.

Keywords:
Fish oil, Antioxidants, Tumour necrosis factor-α, Interleukin 6

Abbreviations:
EPA, eicosapentaenoic acid, DHA, docosahexaenoic acid, IL, interleukin, PBMC, peripheral blood mononuclear cells, PUFA, polyunsaturated fatty acid, TNF, tumour necrosis factor