Hostname: page-component-7dd5485656-bt4hw Total loading time: 0 Render date: 2025-10-31T08:56:20.294Z Has data issue: false hasContentIssue false
  • English
  • Français

Fatty acids and the immune system: from basic science to clinical applications

Published online by Cambridge University Press:  07 March 2007

Parveen Yaqoob
Parveen Yaqoob*
Affiliation:
Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UK
*
Corresponding author: Dr P. Yaqoob, fax + 44 118 931 0800, email P.Yaqoob@reading.ac.uk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Over the last 25 years, the effects of fatty acids on the immune system have been characterized using in vitro, animal and human studies. Advances in fatty acid biochemistry and molecular techniques have recently suggested new mechanisms by which fatty acids could potentially modify immune responses, including modification of the organization of cellular lipids and interaction with nuclear receptors. Possibilities for the clinical applications of n-3 PUFA are now developing. The present review focuses on the hypothesis that the anti-inflammatory properties of n-3 PUFA in the arterial wall may contribute to the protective effects of n-3 PUFA in CVD, as suggested by epidemiological and secondary prevention studies. Studies are just beginning to show that dietary n-3 PUFA can be incorporated into plaque lipid in human subjects, where they may influence the morphology and stability of the atherosclerotic lesion.

Keywords

Fatty acidFish oilImmunityInflammationLymphocyteMacrophage

Information

Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 1 , February 2004 , pp. 89 - 105
Copyright
Copyright © The Nutrition Society 2004

References

Abe, Y, El-Masri, B & Kimball, KT (1998) Soluble adhesion molecules in hypertriglyceridaemia and potential significance on monocyte adhesion. Arteriosclerosis, Thrombosis and Vascular Biology 18, 723–731.CrossRefGoogle ScholarPubMed
Aiello, RJ, Bourassa, PA, Lindsey, S, Weng, W, Freeman, A & Showell, HJ (2002) Leukotriene B4 receptor antagonism reduces monocytic foam cells in mice. Arteriosclerosis, Thrombosis and Vascular Biology 22, 443–449.CrossRefGoogle ScholarPubMed
Albert, CM, Campos, H, Stampfer, MJ, Ridker, PM, Manson, JE, Willett, WC & Ma, J (2002) Blood levels of long-chain n-3 fatty acids and risk of sudden death. New England Journal of Medicine 346, 1113–1118.CrossRefGoogle ScholarPubMed
Albert, CM, Hennekens, CH, O'Donnell, CJ, Ajani, UA, Carey, VJ & Willett, WC (1998) Fish consumption and risk of sudden cardiac death. Journal of the American Medical Association 279, 23–28.CrossRefGoogle ScholarPubMed
Anderson, M & Fritsche, KL (2002) n-3 fatty acids and infectious disease resistance. Journal of Nutrition 132, 3566–3576.CrossRefGoogle ScholarPubMed
Arrington, JL, Chapkin, RS, Switzer, KC, Morriss, JS & McMurray, DN (2001) Dietary polyunsaturated fatty acids modulate purified murine T-cell subset activation. Clinical and Experimental Immunology 125, 499–507.CrossRefGoogle ScholarPubMed
Bandeira-Melo, C, Bozza, P & Weller, PF (2002) The cellular biology of eosinophil eicosanoid formation and function. Journal of Allergy and Clinical Immunology 109, 393–400.CrossRefGoogle ScholarPubMed
Bandeira-Melo, C, Phoofolo, M & Weller, PF (2001) Extranuclear lipid bodies, elicited by CCR3-mediated signaling pathways, are the sites of chemokine-enhanced leukotriene C4 production in eosinophils and basophils. Journal of Biological Chemistry 276, 22779–22787.CrossRefGoogle ScholarPubMed
Berger, A, German, JB, Chiang, BL, Ansari, AA, Keen, CL, Fletcher, MP & Gershwin, MR (1993) Influence of feeding unsaturated fats on growth and immune status of mice. Journal of Nutrition 123, 225–233.Google ScholarPubMed
Billiar, T, Bankey, P, Svingen, B, Curran, RD, West, MA, Holman, RT, Simmons, RL, Cerra, FB (1988) Fatty acid uptake and kupffer cell function: fish oil alters eicosanoid and monokine production to endotoxin stimulation. Surgery 104, 343–349.Google Scholar
Blann, AD & McCollum, CN (1994) Circulating endothelial cell/leukocyte adhesion molecules in cardiovascular disease. Thrombosis and Haemostasis 72, 151–154.Google Scholar
Blok, WL, Deslypere, J-P, Demacker, PNM, van der Ven-Jongekrijg, J, Hectors, MPC, van der Meer, JMW & Katan, MB (1997) Pro- and anti-inflammatory cytokines in healthy volunteers fed various doses of fish oil for 1 year. European Journal of Clinical Investigation 27, 1003–1008.CrossRefGoogle ScholarPubMed
Brouard, C & Pascaud, M (1990) Effects of moderate dietary supplementations with n-3 fatty acids on macrophage and lymphocyte phospholipids and macrophage eicosanoid synthesis in the rat. Biochimica et Biophysica Acta 1047, 19–28.CrossRefGoogle ScholarPubMed
Bucher, HC, Hengstler, P, Schindler, C & Meier, G (2002) N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. American Journal of Medicine 112, 298–304.CrossRefGoogle ScholarPubMed
Burr, ML, Ashfield-Watt, PAL, Dunstan, FDJ, Fehily, AM, Breay, P, Ashton, T, Zotos, PC, Haboubi, NAA & Elwood, PC (2003) Lack of benefit of dietary advice to men with angina: results of a controlled trial. European Journal of Clinical Nutrition 57, 193–200.CrossRefGoogle ScholarPubMed
Burr, ML, Gilbert, JF, Holliday, RM, Elwood, PC, Fehily, AM, Rogers, S, Sweetman, PM & Deadman, NM (1989) Effects of changes in fat, fish and fibre intake on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet ii, 757–761.CrossRefGoogle Scholar
Cadroy, Y, Dupouy, D & Boneu, B (1998) Arachidonic acid enhances the tissue factor expression of mononuclear cells by the cyclooxygenase pathway: beneficial effects of n-3 fatty acids. Journal of Immunology 160, 6145–6150.CrossRefGoogle ScholarPubMed
Calder, PC (1998) Dietary fatty acids and lymphocyte functions. Proceedings of the Nutrition Society 57, 487–502.CrossRefGoogle ScholarPubMed
Calder, PC (2001) Polyunsaturated fatty acids, inflammation and immunity. Lipids 36, 1007–1024.CrossRefGoogle ScholarPubMed
Calder, PC, Bond, JA, Bevan, SJ, Hunt, SV & Newsholme, EA (1991) Effect of fatty acids on the proliferation of concanavalin A-stimulated rat lymph node lymphocytes. International Journal of Biochemistry 23, 579–588.CrossRefGoogle ScholarPubMed
Calder, PC, Bond, JA, Harvey, DJ, Gordon, S & Newsholme, EA (1990) Uptake and incorporation of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis. Biochemical Journal 269, 807–814.CrossRefGoogle ScholarPubMed
Calder, PC, Yaqoob, P, Thies, F, Wallace, FA & Miles, EA (2002) Fatty acids and lymphocyte functions. British Journal of Nutrition 87, S31–S48.CrossRefGoogle ScholarPubMed
Calder, PC & Zurier, RB (2001) Polyunsaturated fatty acids and rheumatoid arthritis. Current Opinion in Clinical Nutrition and Metabolic Care 4, 115–121.CrossRefGoogle ScholarPubMed
Cannon, JG, Fiatarone, MA, Meydani, M, Gong, J, Scott, L, Blimberg, JB & Evans, WJ (1995) Aging and dietary modulation of elastase and interleukin-1 beta secretion. American Journal of Physiology 268, R208–R213.Google ScholarPubMed
Caughey, GE, Mantzioris, E, Gibson, RA, Cleland, LG & James, MG (1996) The effect on human tumour necrosis factor α and interleukin 1β production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. American Journal of Clinical Nutrition 63, 116–122.CrossRefGoogle ScholarPubMed
Caulin-Glaser, T, Farrell, WJ, Pfau, SE, Zaret, B, Bunger, K, Setaro, JF, Brennan, JJ, Bender, JR, Cleman, MW, Cabin, HS & Remetz, MS (1998) Modulation of circulating cellular adhesion molecules in postmenopausal women with coronary artery disease. Journal of the American College of Cardiology 31, 1555–1560.CrossRefGoogle ScholarPubMed
Chan, DC, Watts, GF, Barrett, PHR, Beilin, LJ & Mori, TA (2002) Effect of atorvastatin and fish oil on plasma high sensitivity CRP concentrations in individuals with visceral obesity. Clinical Chemistry 48, 877–883.CrossRefGoogle ScholarPubMed
Chapkin, RS, Akoh, CC & Lewis, RE (1992) Dietary fish oil modulation of in vivo peritoneal macrophage leukotriene production and phagocytosis. Journal of Nutritional Biochemistry 3, 599–604.CrossRefGoogle Scholar
Chapkin, RS, Hubbard, NE & Erickson, KL (1990) 5-Series peptido-leukotriene synthesis in mouse peritoneal macrophages: modulation by dietary n-3 fatty acids. Biochemical and Biophysical Research Communications 171, 764–769.CrossRefGoogle ScholarPubMed
Clark, RB, Bishop-Bailey, D, Estrada-Hernandez, T, Hla, T, Puddington, L & Padula, SJ (2000) The nuclear receptor PPARγ and immunoregulation: PPARγ mediates inhibition of helper T cell responses. Journal of Immunology 164, 1364–1371.CrossRefGoogle ScholarPubMed
Colli, S, Lalli, M, Rise, P, Mussoni, L, Eligini, S, Galli, C & Tremoli, E (1999) Increased thrombogenic potential of human monocyte-derived macrophages spontaneously transformed into foam cells. Thrombosis and Haemostasis 81, 576–581.Google ScholarPubMed
Cooper, AL, Gibbons, L, Horan, MA, Little, RA & Rothwell, NJ (1993) Effect of dietary fish oil supplementation on fever and cytokine production in human volunteers. Clinical Nutrition 12, 321–328.CrossRefGoogle ScholarPubMed
Cunard, R, Ricote, M, DiCampli, D, Clay Archer, D, Kahn, DA, Glass, CK & Kelly, CJ (2002) Regulation of cytokine expression by ligands of peroxisome proliferator activated receptors. Journal of Immunology 168, 2796–2802.Google ScholarPubMed
Danesh, J, Whincup, P, Walker, M, Lennon, L, Thomson, A, Appleby, P, Gallimore, JR & Pepys, MB (2000) Low grade inflammation and coronary heart disease: prospective study and update meta-analyses. British Medical Journal 321, 199–203.CrossRefGoogle ScholarPubMed
Davies, MJ, Richardson, PD, Woolf, N, Katz, DR & Mann, J (1993) Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. British Heart Journal 69, 377–381.CrossRefGoogle ScholarPubMed
Daviglus, ML, Stamler, J, Orencia, AJ, Morris, D & Shekelle, RB (1997) Fish consumption and the 30-year risk of fatal myocardial infarction. New England Journal of Medicine 336, 1046–1053.CrossRefGoogle ScholarPubMed
De Caterina, R, Liao, JK & Libby, P (2000) Fatty acid modulation of endothelial activation. American Journal of Clinical Nutrition 71, Suppl., 213S–223S.CrossRefGoogle ScholarPubMed
DeMaat, MPM, Princen, HMG, Dagneli, PC, Kamperling, SW & Kluft, C (1994) Effect of fish-oil and vitamin E on the cardiovascular risk indicators fibrinogen, C-reactive protein and PA1 activity in healthy-young volunteers. Fibrinolysis 8, 50–52.CrossRefGoogle Scholar
De Pablo, MA, Ortega, E, Gallego, AM, Alvarez, C, Pancorbo, PL, Alavrez de Cienfuegos, G (1998 a) Influence of diets containing olive oil, sunflower oil or hydrogenated coconut oil on the immune response of mice. Journal of Clinical Biochemistry and Nutrition 25, 11–23.CrossRefGoogle Scholar
De Pablo, MA, Ortega, E, Gallego, AM, Alvarez, C, Pancorbo, PL & Alvarez de Cienfuegos, G (1998 b) The effect of dietary fatty acid manipulation on phagocytic activity and cytokine production by peritoneal cells from Balb/c mice. Journal of Nutritional Science and Vitaminology 44, 57–67.CrossRefGoogle ScholarPubMed
Devchand, PR, Keller, H, Peters, JM, Vazquez, M, Gonzalez, FJ & Wajli, W (1996) The PPARa-leukotriene B4 pathway to inflammation control. Nature 384, 39–43.CrossRefGoogle ScholarPubMed
Diaz, O, Berquand, A, Dubois, M, Di Agostino, S, Sette, C, Bourgoin, S, Lagarde, M, Nemoz, G & Prigent, A-F (2002) The mechanism of docosahexaenoic acid-induced phospholipase D activation in human lymphocytes involves exclusion of the enzyme from lipid rafts. Journal of Biological Chemistry 277, 39368–39378.CrossRefGoogle ScholarPubMed
Endres, S, Ghorbani, R, Kelley, VE, Georgilis, K, Lonneman, G, van der Meer, JMW, Cannon, JG, Rogers, TS, Klempner, MS & Weber, PC (1989) The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumour necrosis factor by mononuclear cells. New England Journal of Medicine 320, 265–271.CrossRefGoogle ScholarPubMed
Endres, S, Meydani, SN, Ghorbani, R, Schindler, R & Dinarello, CA (1993) Dietary supplementation with n-3 fatty acids suppresses interleukin-2 production and mononuclear cell proliferation. Journal of Leukocyte Biology 54, 599–603.CrossRefGoogle ScholarPubMed
Fan, Y-Y, McMurray, DN, Ly, LH & Chapkin, RS (2003) Dietary n-3 polyunsaturated fatty acids remodel mouse cell lipid rafts. Journal of Nutrition 133, 1913–1920.CrossRefGoogle ScholarPubMed
Felton, CV, Crook, D, Davies, MJ & Oliver, MF (1997) Relation of plaque lipid composition and morphology to the stability of human aortic plaques. Arteriosclerosis, Thrombosis and Vascular Biology 17, 1337–1345.CrossRefGoogle Scholar
Feskens, EJM, Bowles, CH & Kromhout, D (1993) Association between fish intake and coronary heart disease mortality – differences in normoglycemic and glucose intolerant elderly subjects. Diabetes Care 16, 1029–1034.CrossRefGoogle ScholarPubMed
Finstad, HS, Drevon, CA, Kulseth, MA, Synstad, AV, Knudsen, E & Kolset, SO (1998) Cell proliferation, apoptosis and accumulation of lipid droplets in U937–1 cells incubated with eicosapentaenoic acid. Biochemical Journal 336, 451–459.CrossRefGoogle ScholarPubMed
Forman, BM, Chen, J & Evans, RM (1997) Hypolipidemic drugs, polyunsaturated fatty acids and eicosanoids are ligands for peroxisome prolifertor-activated receptors α and δ. Proceedings of the National Academy of Sciences USA 94, 4312–4317.CrossRefGoogle Scholar
Gallai, V, Sarchielli, P, Trequattrini, A, Franceschini, M, Floridi, A, Firenze, C, Alberti, A, Di Benedetto, D & Stragliotto, E (1993) Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. Journal of Neuroimmunology 56, 143–153.CrossRefGoogle Scholar
GISSI Prevenzione (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 354, 447–455.CrossRefGoogle Scholar
Glass, CK & Witztum, JL (2001) Atherosclerosis: The road ahead. Cell 104, 503–516.CrossRefGoogle ScholarPubMed
Grimble, RF, Howell, WM, O'Reilly, G, Turner, SJ, Markovic, O, Hirrell, S, East, JM & Calder, PC (2002) The ability of fish oil to suppress tumour necrosis factor a production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumour necrosis factor α production. American Journal of Clinical Nutrition 76, 454–459.CrossRefGoogle Scholar
Halvorsen, DA, Hansen, J-B, Grimsgaard, S, Bonna, KH, Kierulf, P & Nordoy, A (1997) The effect of highly purified eicosapentaenoic and docosahexaenoic acids on monocyte phagocytosis in man. Lipids 32, 935–942.CrossRefGoogle ScholarPubMed
Harris, SG & Phipps, RP (2001) The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis. European Journal of Immnuology 31, 1098–1105.3.0.CO;2-I>CrossRefGoogle Scholar
Harris, WS (1996) N-3 fatty acids and lipoproteins: comparison of results from human and animal studies. Lipids 31, 243–252.CrossRefGoogle ScholarPubMed
Haught, WH, Mansour, M, Rothlein, R, Kishimoto, TK, Mainolfi, EA, Hendricks, JB, Hendricks, C & Mehta, JL (1996) Alterations in circulating intercellular adhesion molecule-1 and L-selectin: further evidence for chronic inflammation in ischemic heart disease. American Heart Journal 132, 1–8.CrossRefGoogle ScholarPubMed
Hayashi, N, Tashiro, T, Yamamori, H, Takagi, K, Morishima, Y, Otsubo, Y, Sugiura, T, Furukawa, K, Nitta, H, Nakajima, N, Suzuki, N & Ito, I (1998) Effects of intravenous omega-3 and omega-6 fat emulsion on cytokine production and delayed type hypersensitivity in burned rats receiving total parenteral nutrition. Journal of Parenteral and Enteral Nutrition 22, 363–367.CrossRefGoogle ScholarPubMed
Heyland, DK, Novak, F, Drover, JW, Jain, M, Su, X & Suchner, U (2001) Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. Journal of the American Medical Association 286, 944–953.CrossRefGoogle ScholarPubMed
Horejsi, V (2003) The roles of membrane microdomains (rafts) in T cell activation. Immunology Reviews 191, 148–164.CrossRefGoogle ScholarPubMed
Hu, FB, Bronner, L, Willett, WC, Stampfer, MJ, Rexrode, KM, Albert, CM, Hunter, D & Manson, JE (2002) Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. Journal of the American Medical Association 287, 1815–1821.CrossRefGoogle ScholarPubMed
Hughes, DA, Pinder, AC, Piper, Z, Johnson, IT & Lund, EK (1996 a) Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes. American Journal of Clinical Nutrition 63, 267–272.CrossRefGoogle ScholarPubMed
Hughes, DA, Southon, S & Pinder, AC (1996b) n-3 Polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes in vitro. Journal of Nutrition 126, 603–610.CrossRefGoogle ScholarPubMed
Jeffery, NM, Yaqoob, P, Newsholme, EA & Calder, PC (1996) The effects of olive oil upon rat serum lipid levels and lymphocyte functions are due to oleic acid. Annals of Nutrition and Metabolism 40, 71–80.CrossRefGoogle ScholarPubMed
Jiang, C, Ting, AT & Seed, B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 82–86.CrossRefGoogle ScholarPubMed
Johansen, O, Seljeflot, I, Hostmark, AT & Arnesen, H (1999) The effect of supplementation with omega-3 fatty acids on soluble markers of endothelial function in patients with coronary heart disease. Arteriosclerosis, Thrombosis and Vascular Biology 19, 1681–1686.CrossRefGoogle ScholarPubMed
Jolly, CA, Jiang, Y-H, Chapkin, RS & McMurray, DN (1997) Dietary n-3 polyunsaturated fatty acids suppress murine lymphoproliferation, interleukin-2 secretion and the formation of diacylglycerol and ceramide. Journal of Nutrition 127, 37–43.CrossRefGoogle ScholarPubMed
Jolly, CA, McMurray, DN & Chapkin, RS (1998) Effect of dietary n-3 polyunsaturated fatty acids on interleukin-2 and interleukin-2 receptor-α expression on activated nurine lymphocytes. Prostaglandins, Leukotrienes and Essential Fatty Acids 58, 289–293.CrossRefGoogle Scholar
Jones, DC, Manning, BM & Daynes, RA (2002) A role for the peroxisome proliferator-activated receptor α in T cell physiology and ageing immunobiolgy. Proceedings of the Nutrition Society 61, 363–369.CrossRefGoogle Scholar
Katagiri, YU, Kiyokawa, N & Fujimoto, J (2001) A role for lipid rafts in immune cell signalling. Microbiology and Immunology 45, 1–8.CrossRefGoogle Scholar
Kelley, DS, Taylor, PC, Nelson, GJ & Mackey, BE (1998) Dietary docosahexaenoic acid and immunocompetence in young healthy men. Lipids 33, 559–566.CrossRefGoogle ScholarPubMed
Kelley, DS, Taylor, PC, Nelson, GJ, Schmidt, PC, Ferretti, A, Erickson, KL, Yu, R & Chandra, RK (1999) Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 34, 317–324.CrossRefGoogle ScholarPubMed
Kew, S, Mesa, MD, Tricon, S, Buckley, R, Minihane, AM & Yaqoob, P (2004) Effects of eicosapentaenoic and docosahexaenoic acid-rich oils on immune cell composition and function in healthy humans. American Journal of Clinical Nutrition (In the Press).CrossRefGoogle Scholar
Kliewer, SA, Sundseth, SS, Jones, SA, Brown, PJ, Wisely, GB, Koble, CS, Devchand, P, Wahli, W, Willson, TM, Lenhard, JM & Lehmann, JM (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ. Proceedings of the National Academy of Sciences USA 94, 4318–4323.CrossRefGoogle ScholarPubMed
Koenig, W, Sund, M & Froelich, M (1999) C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA Augsburg Cohort Study, 1984 to 1992. Circulation 99, 237–242.CrossRefGoogle Scholar
Krey, G, Braissant, O, L'Horset, F, Kalkhoven, E, Perroud, M, Parker, MG & Wahli, W (1997) Fatty acids, eicosanoids and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Molecular Endocrinology 11, 779–791.CrossRefGoogle ScholarPubMed
Kromhout, D, Bosschieter, EB & Coulander, CL (1985) The inverse relationship between fish consumption and 20-year mortality from coronary heart disease. New England Journal of Medicine 312, 1205–1209.CrossRefGoogle Scholar
Kromhout, D, Feskens, EJM & Bowles, CH (1995) The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population. International Journal of Epidemiology 24, 340–345.CrossRefGoogle Scholar
Kuller, LH, Tracy, RP & Shaten, J (1996) For the MRFIT Group. Relationship of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. American Journal of Epidemiology 144, 537–547.Google Scholar
Leaf, A, Kang, JX, Xiao, X-F & Billman, GE (1998) Dietary n-3 fatty acids in the prevention of cardiac arrhythmias. Current Opinion in Clinical Nutrition and Metabolic Care 1, 225–228.CrossRefGoogle ScholarPubMed
Lee, TH, Hoover, RL, Williams, JD, Sperling, RI, Ravalese, J, Spur, BW, Robinson, DR, Corey, EJ, Lewis, RA & Austen, KF (1985) Effects of dietary enrichment with eicosapentaenoic acid and docosahexaenoic acid on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. New England Journal of Medicine 312, 1217–1224.CrossRefGoogle ScholarPubMed
Liang, XQ, Nazarian, A, Erdjument-Bromage, H, Bornmann, W, Tempst, P & Resch, MD (2001) Heterogeneous fatty acylation of Src family kinases with polyunsaturated fatty acids regulates raft localization and signal transduction. Journal of Biological Chemistry 276, 30987–30994.CrossRefGoogle ScholarPubMed
Libby, P, Geng, YJ, Aikawa, M, Schoenbeck, U, Mach, F, Clinton, SK, Sukhova, GK & Lee, RT (1996) Macrophages and atherosclerotic plaque stability. Current Opinion in Lipidology 7, 330–335.CrossRefGoogle ScholarPubMed
Lin, Q, Ruuska, SE, Shaw, NS, Dong, D & Noy, N (1999) Ligand selectivity of the peroxisome proliferator-activated receptor α. Biochemistry 38, 185–190.CrossRefGoogle ScholarPubMed
Magrum, LJ & Johnston, PV (1983) Modulation of prostaglandin synthesis in rat peritoneal macrophages with ω-3 fatty acids. Lipids 18, 514–521.CrossRefGoogle ScholarPubMed
Malik, I, Danesh, J, Whincup, P, Bhatia, V, Papacosta, O, Walker, M, Lennon, L, Thomson, A & Haskard, D (2001) Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis. Lancet 358, 971–975.CrossRefGoogle ScholarPubMed
Mantzioris, E, Cleland, LG, Gibson, RA, Neumann, MA, Demasi, M & James, MJ (2000) Biochemical effects of a diet containing foods enriched with n-3 fatty acids. American Journal of Clinical Nutrition 72, 42–48.CrossRefGoogle ScholarPubMed
Marchioli, R, Barzi, F, Bomba, E, Chieffo, C, Di Gregorio, D, Di Mascio, R et al. (2002) Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction. Circulation 105, 1897–1903.CrossRefGoogle ScholarPubMed
Meade, CJ & Mertin, J (1978) Fatty acids and immunity. Advances in Lipid Research 16, 127–165.CrossRefGoogle ScholarPubMed
Mendall, MA, Starchan, DP & Butland, BK (2000) C-reactive protein: relation to toal mortality, cardiovascular mortality and cardiovascular risk factors in men. European Heart Journal 21, 1584–1590.CrossRefGoogle Scholar
Meydani, SN, Endres, S, Woods, MM, Goldin, BR, Soo, C, Morrill-Labrode, A, Dinarello, CA & Gorbach, SL (1991) Oral n-3 fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. Journal of Nutrition 121, 547–555.CrossRefGoogle Scholar
Miettinen, TA, Naukkaninen, V, Hattinen, JK, Mathial, S & Kumlin, T (1982) Fatty acid composition of plasma predicts myocardial infarction. British Medical Journal 285, 993–996.CrossRefGoogle Scholar
Miles, EA, Thies, F, Wallace, FA, Powell, JR, Hurst, TL, Newsholme, EA & Calder, PC (2001) Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations. Clinical Science 100, 91–100.CrossRefGoogle ScholarPubMed
Miles, EA, Wallace, FA & Calder, PC (2000) Dietary fish oil reduces intercellular adhesion molecule 1 and scavenger receptor expression on murine macrophages. Atherosclerosis 152, 43–50.CrossRefGoogle ScholarPubMed
Molvig, J, Pociot, F, Worsaae, H, Wogensen, LD, Baek, L & Christensen, P (1991) Dietary supplementation with omega-3 polyunsaturated fatty acids decreases mononuclear cell proliferation and interleukin 1β content, but not monokine secretion in healthy and insulin-dependent diabetic individuals. Scandinavian Journal of Immunology 34, 399–410.CrossRefGoogle Scholar
Morisaki, N, Saito, I, Tamura, K, Tashiro, J, Masuda, M, Kanzaki, T, Watanabe, S, Masuda, Y & Saito, Y (1997) New indices of ischemic heart disease and ageing: studies on the serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion. Molecule-1 (VCAM-1) in patients with hypercholesterolemia and ischemic heart disease. Atherosclerosis 131, 43–48.CrossRefGoogle ScholarPubMed
Norell, S, Ahlbom, A, Feychling, M & Pederen, NL (1986) Fish consumption and mortality from coronary heart disease. British Medical Journal 293, 426.CrossRefGoogle ScholarPubMed
Peterson, LD, Jeffery, NM, Thies, F, Sanderson, P, Newsholme, EA & Calder, PC (1998 a) Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity. Lipids 22, 171–180.CrossRefGoogle Scholar
Peterson, LD, Thies, F, Sanderson, P, Newsholme, EA & Calder, PC (1998 b) Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of fish oil upon rat lymphocytes. Life Sciences 62, 2209–2217.CrossRefGoogle ScholarPubMed
Pierce, SK (2002) Lipid rafts and B cell activation. Nature Reviews Immunology 2, 96–105.CrossRefGoogle ScholarPubMed
Pietsch, A, Weber, C, Goretzki, M, Weber, PC & Lorenz, RL (1995) N-3 but not n-6 fatty acids reduce the expression of the combined adhesion and scavenger receptor CD36 in human monocytic cells. Cell Biochemistry and Function 13, 211–216.CrossRefGoogle Scholar
Plutzky, J (1999) Atherosclerotic plaque rupture: emerging insights and opportunities. American Journal of Cardiology 84, 15J–20J.CrossRefGoogle Scholar
Puertollano, MA, de Pablo, MA & Alvarez de Cienfuegos, G (2002) Relevance of dietary lipids as modulators of immune functions in cells infected with Listeria monocytogenes. Clinical Diagnostics and Laboratory Immunology 9, 352–357.Google ScholarPubMed
Rapp, JH, Connor, WE, Lin, DS & Porter, JM (1991) Dietary eicosapentaenoic acid and docosahexaenoic acid from fish oil – their incorporation into advanced atherosclerotic plaques. Arteriosclerosis and Thrombosis 11, 903–911.CrossRefGoogle Scholar
Renier, G, Skamene, E, de Sanctis, J & Radzioch, D (1993) Dietary n-3 polyunsaturated fatty acids prevent the development of atherosclerotic lesions in mice: modulation of macrophage secretory activities. Arteriosclerosis and Thrombosis 13, 1515–1524.CrossRefGoogle ScholarPubMed
Ridker, PM, Buring, JE & Shih, J (1998) Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 97, 425–428.CrossRefGoogle Scholar
Ridker, PM, Hennekens, CH, Buring, JE & Rifai, N (2000) C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New England Journal of Medicine 342, 836–843.CrossRefGoogle Scholar
Ross, R (1999) Atherosclerosis – an inflammatory disease. New England Journal of Medicine 340, 115–126.CrossRefGoogle ScholarPubMed
Rothlein, R, Mainolfi, EA, Czajkowski, M & Martin, SD (1991) A form of circulating ICAM-1 in human serum. Journal of Immunology 147, 3788–3793.CrossRefGoogle ScholarPubMed
Sadeghi, S, Wallace, FA & Calder, PC (1999) Dietary lipids modify the cytokine response to bacterial lipopolysaccharide in mice. Immunology 96, 404–410.CrossRefGoogle ScholarPubMed
Sanderson, P, MacPherson, GG, Jenkins, CH & Calder, PC (1998) Dietary fish oil diminishes lymphocyte adhesion to macrophage and endothelial cell monolayers. Immunology 94, 79–87.CrossRefGoogle ScholarPubMed
Sanderson, P, Yaqoob, P & Calder, PC (1995 a) Effects of dietary lipid manipulation upon rat spleen lymphocyte functions and expression of cell surface molecules. Journal of Nutritional and Environmental Medicine 5, 119–132.CrossRefGoogle Scholar
Sanderson, P, Yaqoob, P & Calder, PC (1995 b) Effects of dietary lipid manipulation upon graft vs. host and host vs. graft responses in the rat. Cellular Immunology 164, 240–247.CrossRefGoogle ScholarPubMed
Schmidt, EB, Varming, K, Moller, JM, Bulow Pederson, I, Madsen, P & Dyerberg, J (1996) No effect of a very low dose of n-3 fatty acids on monocyte function in healthy humans. Scandinavian Journal of Clinical Investigation 56, 87–92.CrossRefGoogle ScholarPubMed
Schmidt, EB, Varming, K, Pederson, JO, Lervang, HH, Grunnet, N, Jersild, C & Dyerberg, J (1992) Long term supplementation with n-3 fatty acids. II. Effect on neutrophil and monocyte chemotaxis. Scandanavian Journal of Clinical and Laboratory Investigation 52, 229–236.CrossRefGoogle ScholarPubMed
Seljeflot, I, Arnesen, H, Brude, IR, Nenseter, MS, Drevon, CA & Hjermann, I (1998) Effects of omega-3 fatty acids and/or antioxidants on endothelial cell markers. European Journal of Clinical Investigation 28, 629–635.CrossRefGoogle ScholarPubMed
Shekelle, RB, Missell, L, Paul, O, Shryock, AM & Stamler, J (1985) Fish consumption and mortality from coronary heart disease. New England Journal of Medicine 313, 820.Google Scholar
Simons, K & Ikonen, E (1997) Functional rafts in cell membranes. Nature 387, 569–572.CrossRefGoogle ScholarPubMed
Simons, K & Toomre, D (2000) Lipid rafts and signal transduction. Nature Reviews 1, 31–39.CrossRefGoogle ScholarPubMed
Singh, RB, Niaz, MA, Sharma, JP, Kumar, R, Rastogi, V & Moshiri, M (1997) Randomised double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival. Cardiovascular Drugs and Therapy 11, 85–91.Google ScholarPubMed
Siscovick, DS, Raghunathan, TE, King, I, Weinmann, S, Wicklund, KG, Albright, J et al. (1995) Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. Journal of the American Medical Association 274, 1363–1367.CrossRefGoogle ScholarPubMed
Soyland, E, Lea, T, Sandstad, B & Drevon, CA (1994) Dietary supplementation with very long chain n-3 fatty acids in man decreases expression of the interleukin-1 receptor (CD25) on mitogen-stimulated lymphocytes from patients with inflammatory skin diseases. European Journal of Clinical Investigation 24, 236–242.CrossRefGoogle Scholar
Sperling, RI, Benincaso, AI, Knoell, CT, Larkin, JK, Austen, KF & Robinson, DR (1993) Dietary ω-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. Journal of Clinical Investigation 91, 651–660.CrossRefGoogle ScholarPubMed
Stulnig, TM, Huber, J, Leitinger, N, Imre, E-M Angelisoval, P, Nowotny, P & Waldhausl, W (2001) Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition. Journal of Biological Chemistry 276, 37335–37340.CrossRefGoogle ScholarPubMed
Taki, H, Morinaga, SI, Yamazaki, K, Hamazaki, T, Suzuki, H & Nakamura, N (1992) Reduction of delayed-type hypersensitivity by the injection of n-3 polyunsaturated fatty acids in mice. Transplantation 54, 511–514.CrossRefGoogle ScholarPubMed
Tan, NS, Shaw, NS, Vinckenbosch, N, Liu, P, Yasmin, R, Desvergne, B, Wahli, W & Noy, N (2002) Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Molecular and Cellular Biology 22, 5114–5127.CrossRefGoogle ScholarPubMed
Tashiro, T, Yamamori, H, Takagi, K, Hayashi, N, Furukawa, K & Nakajima, N (1998) n-3 versus n-6 polyunsaturated fatty acids in critical illness. Nutrition 14, 551–553.CrossRefGoogle ScholarPubMed
Thies, F, Garry, JMC, Yaqoob, P, Rerkasem, K, Williams, J, Shearman, C, Gallagher, PJ, Calder, PC & Grimble, RF (2003) Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 361, 477–485.CrossRefGoogle ScholarPubMed
Thies, F, Nebe-von-Caron, G, Powell, JR, Yaqoob, P, Newsholme, EA & Calder, PC (2001 a) Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55y. American Journal of Clinical Nutrition 73, 539–548.CrossRefGoogle Scholar
Thies, F, Nebe-von-Caron, G, Powell, JR, Yaqoob, P, Newsholme, EA, Calder, PC (2001 b) Dietary supplementation with γ-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. Journal of Nutrition 131, 1918–1927.CrossRefGoogle ScholarPubMed
Tomobe, YI, Morizawa, K, Tsuchida, M, Hibino, H, Nakano, Y & Tanaka, Y (2000) Dietary docosahexaenoic acid suppresses inflammation and immunoresponses in contact hypersensitivity reaction in mice. Lipids 35, 61–69.CrossRefGoogle ScholarPubMed
Tracy, RP (1998) Inflammation in cardiovascular disease; cart, horse or both? Circulation 97, 2000–2002.CrossRefGoogle ScholarPubMed
Tracy, RP, Lemaitre, RN & Psaty, BM (1997) Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health Study and the Rural Health Promotion Project. Arteriosclerosis, Thrombosis and Vascular Biology 17, 1121–1127.CrossRefGoogle ScholarPubMed
Volker, DH, FitzGerald, PEB & Garg, ML (2000) The eicosapentaenoic to docosahexaenoic acid ratio of diets affects the pathogenesis of arthritis in Lew/SSN rats. Journal of Nutrition 130, 559–565.CrossRefGoogle ScholarPubMed
Wachtler, P, Konig, W, Senkal, M, Kemen, M & Koller, M (1997) Influence of a total parenteral nutrition enriched with ω-3 fatty acids on leukotriene synthesis of peripheral leukocytes and systemic cytokine levels in patients with major surgery. Journal of Trauma 42, 191–198.CrossRefGoogle ScholarPubMed
Wallace, FA, Miles, EA & Calder, PC (2000 a) Activation state alters the effect of dietary lipids on proinflammatory mediator production by murine macrophages. Cytokine 12, 1374–1379.CrossRefGoogle ScholarPubMed
Wallace, FA, Miles, EA, Evans, C, Stock, TE, Yaqoob, P & Calder, PC (2001) Dietary fatty acids influence the production of Th1- but not Th2-type cytokines. Journal of Leukocyte Biology 69, 449–457.CrossRefGoogle Scholar
Wallace, FA, Neely, SJ, Miles, EA & Calder, PC (2000 b) Dietary fats affect macrophage-mediated cytotoxicity towards tumour cells. Immunology and Cell Biology 78, 40–48.CrossRefGoogle ScholarPubMed
Webb, Y, Hermida-Matsumoto, L & Resch, MD (2000) Inhibition of protein palmitoylation, raft localization and T cell signalling by 2-bromopalmitate and polyunsaturated fatty acids. Journal of Biological Chemistry 275, 261–270.CrossRefGoogle Scholar
Whelan, J, Broughton, KS, Lokesh, B & Kinsella, JE (1991) In vivo formation of leukotriene E5 by murine peritoneal cells. Prostaglandins 41, 29–42.CrossRefGoogle ScholarPubMed
Williams, CM (1997) Postprandial lipid metabolism: effects of dietary fatty acids. Proceedings of the Nutrition Society 56, 679–692.CrossRefGoogle ScholarPubMed
Wolfrum, C, Bormann, CM, Borchers, T & Spener, F (2001) Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors α- and γ-mediated gene expression via liver fatty acid binding protein: a signaling path to the nucleus. Proceedings of the National Academy of Sciences USA 98, 2323–2328.CrossRefGoogle ScholarPubMed
Xu, HE, Lambert, MH, Montana, VG, Plunket, KD, Moore, LB, Collins, JL, Oplinger, JA, Kliewer, SA, Gampe, RT, McKee, DD Moore, JT & Willson, TM (2001) Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proceedings of the National Academy of Sciences USA 98, 13919–13924.CrossRefGoogle ScholarPubMed
Yaqoob, P (2002) Monounsaturated fatty acids and immune function. European Journal of Clinical Nutrition 56, S9–S13.CrossRefGoogle ScholarPubMed
Yaqoob, P (2003 a) Fatty acids as gatekeepers of immune cell regulation. Trends in Immunology 24, 639–645.CrossRefGoogle ScholarPubMed
Yaqoob, P (2003 b) Lipids and the immune response: from molecular mechanisms to clinical applications. Current Opinion in Clinical Nutrition and Metabolic Care 6, 133–150.CrossRefGoogle ScholarPubMed
Yaqoob, P & Calder, PC (1995 a) Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. Cellular Immunology 163, 120–128.CrossRefGoogle ScholarPubMed
Yaqoob, P & Calder, PC (1995 b) The effects of dietary lipid manipulation on the production of murine T-cell-derived cytokines. Cytokine 7, 548–553.CrossRefGoogle ScholarPubMed
Yaqoob, P, Knapper, JA, Webb, DH, Williams, CM, Newsholme, CM & Calder, PC (1998) Effect of olive oil on immune function in middle aged men. American Journal of Clinical Nutrition 67, 129–135.CrossRefGoogle ScholarPubMed
Yaqoob, P, Newsholme, EA & Calder, PC (1994 a) The effect of dietary lipid manipulation on rat lymphocyte subsets and proliferation. Immunology 82, 603–610.Google ScholarPubMed
Yaqoob, P, Newsholme, EA & Calder, PC (1994 b) Inhibition of natural killer cell activity by dietary lipids. Immunology Letters 41, 241–247.CrossRefGoogle ScholarPubMed
Yaqoob, P, Newsholme, EA & Calder, PC (1995 a) The effect of fatty acids on leukocyte subsets and proliferation in whole blood. Nutrition Research 15, 279–287.CrossRefGoogle Scholar
Yaqoob, P, Newsholme, EA & Calder, PC (1995 b) Influence of cell culture conditions on diet-induced changes in lymphocyte fatty acid composition. Biochimica et Biophysica Acta 1255, 333–340.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, 600–605.CrossRefGoogle ScholarPubMed
Yaqoob, P, Pala, HS, Cortina-Borja, M, Newsholme, EA & Calder, PC (2000) Encapsulated fish oil enriched in α-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell function. European Journal of Clinical Investigation 30, 260–274.CrossRefGoogle ScholarPubMed
Yudkin, JS, Kumari, M, Humphries, SE, Mohamed-Ali, V (2000) Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148, 209–214.CrossRefGoogle ScholarPubMed
Zeyda, M, Staffler, G, Horejsi, V, Waldhausl, W & Stulnig, TM (2002) LAT displacement from lipid rafts as a molecular mechanism for the inhibition of T cell signalling by polyunsaturated fatty acids. Journal of Biological Chemistry 277, 28418–28423.CrossRefGoogle ScholarPubMed
Zhang, W, Trible, RP & Samelson, LE (1998) LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation. Immunity 9, 239–246.CrossRefGoogle ScholarPubMed
Zlatkine, P, Mehul, B & Magee, AI (1997) Retargeting of cytosolic proteins to the plasma membrane by the Lck protein tyrosine kinase dual acylation motif. Journal of Cell Science 110, 673–679.CrossRefGoogle Scholar