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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

Published online by Cambridge University Press:  09 March 2007

Timothy Trebble*
Affiliation:
The Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Nigel K. Arden
Affiliation:
MRC Environmental Epidemiology Unit, University of Southampton, Tremona Road, Southampton General Hospital, Southampton SO16 6YD, UK
Mike A. Stroud
Affiliation:
The Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Stephen A. Wootton
Affiliation:
The Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Graham C. Burdge
Affiliation:
The Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Elizabeth A. Miles
Affiliation:
The Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Anne B. Ballinger
Affiliation:
Department of Adult and Paediatric Gastroenterology, Barts and the London, Queen Mary's School of Medicine and Dentistry, University of London, London E1 2AD, UK
Rachel L. Thompson
Affiliation:
The Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Philip C. Calder
Affiliation:
The Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
*
*Corresponding author: T. Trebble, fax +44 2380 794945, email [email protected]
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Abstract

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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.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2003

References

Allard, JP, Kurian, R, Aghdassi, E, Muggli, R & Royall, D (1997) Lipid peroxidation during n-3 fatty acid and vitamin E supplementation in humans. Lipids 32, 535541.CrossRefGoogle ScholarPubMed
Blonk, MC, Bilo, HJG, Naua, JJP, Popp-Snijders, C, Mulder, C & Donker, AJM (1990) Dose response effects of fish oil supplementation in healthy volunteers. Am J Clin Nutr 52, 120127.CrossRefGoogle ScholarPubMed
British Nutrition Foundation (1999) In Briefing Paper: n-3 Fatty Acids and Health. London: BNF.Google Scholar
Burdge, GC, Wright, P, Jones, AE & Wootton, SA (2000) A method for separation of phosphatidylcholine, triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid-phase extraction. Br J Nutr 84, 781787.CrossRefGoogle ScholarPubMed
Calder, PC (1997) n-3 Polyunsaturated fatty acid and cytokine production in health and disease. Ann Nutr Metabol 41, 203234.CrossRefGoogle ScholarPubMed
Calder, PC (2001) n-3 Polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled water or another fishy tale? Nutr Res 21, 309341.CrossRefGoogle Scholar
Calder, PC, Yaqoob, P, Thies, F, Wallace, FA & Miles, EA (2002) Fatty acids and lymphocyte functions. Br J Nutr 87, Suppl. 1, S31S48.CrossRefGoogle ScholarPubMed
Cannon, JG, Fiatarone, MA & Meydani, M (1995) Aging and dietary modulation of elastase and interleukin-1 beta secretion. Am J Physiol 268, R208R213.Google ScholarPubMed
Caughey, GE, Mantzioris, E, Gibson, RA, Cleland, LG & James, MJ (1996) The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 63, 116122.CrossRefGoogle ScholarPubMed
Committee on Medical Aspects of Food Policy (1991) Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. Report on Health and Social Subjects. no. 41 London: H. M. Stationery Office.Google Scholar
De Pablo, M & De Cienfuegos, GA (2000) Modulatory effects of dietary lipids on immune system functions. Immunol Cell Biol 78, 3139.CrossRefGoogle ScholarPubMed
Elliott, MJ, Feldmann, M & Maini, RN (1995) TNF alpha blockade in rheumatoid arthritis: rationale, clinical outcomes and mechanisms of action. Int J Immunopharmacol 17, 141145.CrossRefGoogle ScholarPubMed
Endres, S, Ghorbani, R & Kelley, VE (1989) The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. New Eng J Med 320, 265271.CrossRefGoogle ScholarPubMed
Folch, J, Lees, M & Sloane-Stanley, GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226, 497509.CrossRefGoogle ScholarPubMed
Gallai, V, Sarchielli, P & Trequattrini, A (1995) Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol 56, 143153.Google Scholar
Gibney, MJ & Hunter, B (1993) The effects of short- and long-term supplementation with fish oil on the incorporation of n-3 polyunsaturated fatty acids into cells of the immune system in healthy volunteers. Eur J Clin Nutr 47, 255259.Google Scholar
Grimm, H, Mayer, K, Mayser, P & Eigenbrodt, E (2002) The regulatory potential of n-3 fatty acids in immunological and inflammatory processes. Br J Nutr 87, Suppl. 1, S59S67.CrossRefGoogle ScholarPubMed
Haglund, O, Luostarinen, R, Wallin, R, Wibell, L & Saldeen, T (1991) The effects of fish oil on triglycerides, cholesterol, fibrinogen and malonaldehyde in humans supplemented with vitamin E. J Nutr 121, 165169.Google Scholar
Harats, D, Dabach, Y, Hollander, G et al. (1991) Fish oil ingestion in smokers and nonsmokers enhances peroxidation of plasma lipoproteins. Atheroscherosis 90, 127139.Google Scholar
Healy, DA, Wallace, FA, Miles, EA, Calder, PC & Newsholme, P (2000) Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids 35, 763768.CrossRefGoogle ScholarPubMed
Jacob, CO, Fronek, Z, Lewis, GD, Koo, M, Hansen, JA & McDevitt, HO (1990) Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. Proc Natl Acad Sci USA 87, 12331237.CrossRefGoogle ScholarPubMed
Lee, TH, Hoover, RL, Williams, JD et al. (1985) Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. New Eng J Med 312, 12171224.CrossRefGoogle ScholarPubMed
Maes, M, Stevens, W, Scharpe, S et al. (1994) Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6, and soluble interleukins-2 and -6 receptor concentrations in normal volunteers. Experientia 50, 821829.CrossRefGoogle Scholar
Meydani, SN, Endres, S, Woods, MM et al. (1991 a) Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr 121, 547555.Google Scholar
Meydani, M, Natiello, F, Goldin, B et al. (1991 b) Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women. J Nutr 121, 484491.CrossRefGoogle ScholarPubMed
Molvig, J, Pociot, F, Worsaae, H et al. (1991) Dietary supplementation with omega-3-polyunsaturated fatty acids decreases mononuclear cell proliferation and interleukin-1 beta content but not monokine secretion in healthy and insulin-dependent diabetic individuals. Scand J Immunol 34, 399410.Google Scholar
Palozzo, P, Sgarlata, E & Luberto, C (1996) n-3 Fatty acids induce oxidative modifications in human erythrocytes depending on dose and duration of dietary supplementation. Am J Clin Nutr 64, 297304.CrossRefGoogle Scholar
Sevanian, A & Hochstein, P (1985) Mechanisms and consequences of lipid peroxidation in biological systems. Annu Rev Nutr 5, 365390.CrossRefGoogle ScholarPubMed
Shaheen, SO, Sterne, JAC, Thompson, RL, Songhurst, CE, Margetts, BM & Burney, PGJ (2001) Dietary antioxidants and asthma in adults. Population-based case–control study. Am J Respir Crit Care Med 164, 18231828.Google Scholar
Targan, SR, Hanauer, SB, van Deventer, SJ et al. (1997) A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. New Eng J Med 337, 10291035.Google Scholar
Thies, F, Miles, EA, Nebe-von-Caron, G, Powell, JR et al. (2001) Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy humans. Lipids 36, 11831193.CrossRefGoogle ScholarPubMed
Thies, F, Nebe-von-Caron, G, Powell, JR, Yaqoob, P, Newsholme, EA & Calder, PC (2001) Dietary supplementation with gamma linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. J Nutr 131, 19181927.CrossRefGoogle ScholarPubMed
Yaqoob, P, Newsholme, EA & Calder, PC (1999) Comparison of cytokine production in cultures of whole human blood and purified mononuclear cells. Cytokine 11, 600605.CrossRefGoogle ScholarPubMed
Yaqoob, P, Pala, HS, Cortina-Borja, M, Newsholme, EA & Calder, PC (2000) Encapsulated fish oil enriched in alpha-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. Eur J Clin Invest 30, 260274.CrossRefGoogle Scholar