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Immunomodulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids

Published online by Cambridge University Press:  28 February 2007

Philip C. Calder*
Affiliation:
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, Oxford OX1 3QU
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Abstract

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Type
Sir David Cuthbertson Medal Lecture
Copyright
Copyright © The Nutrition Society 1996

References

Ailhaud, G., Amri, E.-Z. & Grimaldi, P.-A. (1995). Fatty acids and adipose cell differentiation. Prostaglandins, Leukotrienes and Essential Fatty Acids 48, 113115.CrossRefGoogle Scholar
Albina, J. E., Gladden, P. & Walsh, W. R. (1993). Detrimental effects of an ω-3 fatty acid-enriched diet on wound healing. Journal of Parentera1 and Enteral Nutrition 17, 519521.Google Scholar
Alexander, N. J. & Smythe, N. L. (1988). Dietary modulation of in vitro lymphocyte function. Annals of Nutrition and Metabolism 32, 192199.CrossRefGoogle ScholarPubMed
Allen, B. R., Maurice, P. D. L., Goodfield, M. W., Cockbill, S. & Stammers, J. (1985). The effect on psoriasis of dietary supplementation with eicosapentaenoic acid. British Journal of Dermatology 113, 777.Google Scholar
Anel, A., Naval, J., Gonzalez, B., Torres, J. M., Mishal, Z., Uriel, J. & Pinciro, A. (1990). Fatty acid metabolism in human lymphocytes. I. Time course changes in fatty acid composition and membrane fluidity during blastic transformation of peripheral blood lymphocytes. Biochimica et Biophysica Acta 1044, 323331.Google Scholar
Atkinson, H. A. C. & Maisey, J. (1995). Effects of high levels of dietary oils on autoimmune responses. Biochemical Society Transactions 23, 277S.Google Scholar
Badwey, J. A., Curnutte, J. T., Robinson, J. M., Berde, C. B., Karnovsky, M. J. & Karnovsky, M. L. (1984). Effects of free fatty acids on release of superoxide and on change of shape by neutrophils. Journal of Biological Chemistry 259, 78707877.CrossRefGoogle ScholarPubMed
Baldie, G., Kaimakamis, D. & Rotondo, D. (1993). Fatty acid modulation of cytokine release from human monocytic cells. Biochimica et Biophysica Acta 1179, 125133.Google Scholar
Bates, D., Cartlidge, N. E. F., French, J. M., Jackson, M. J., Nightingale, S., Shaw, D. A., Smith, S., Woo, E., Hawkins, S. A., Millar, J. H. D., Belin, J., Conroy, D. M., Gill, S. K., Sidey, M., Smith, A. D., Thompson, R. H. S., Zilkha, K., Gale, M. & Sinclair, H. M. (1989). A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry 52, 1822.CrossRefGoogle ScholarPubMed
Bell, M. V. & Sargent, J. R. (1987). Effects of the fatty acid composition of phosphatidylserine and diacylglycerol on the in vitro activity of protein kinase C from rat spleen: influence of (n-3)and (n-6) polyunsaturated fatty acids. Comparative Biochemistry and Physiology 86B, 227232.Google Scholar
Bennett, W. M., Carpenter, C. B., Shapiro, M. E., Strom, T. B., Hefty, D., Tillman, M., Abrams, J., Ryan, D. & Kelley, V. A. (1995). Delayed omega-3 fatty acid supplements in renal transplantation. Transplantation 59, 352356.Google Scholar
Berger, A., German, J. B., Chiang, B. L., Ansari, A. A., Keen, C. L., Fletcher, M. P. & Gershwin, M. R. (1993). Influence of feeding unsaturated fats on growth and immune status of mice. Journal of Nutrition 123, 225233.Google ScholarPubMed
Berthou, L., Saladin, R., Yaqoob, P., Branellec, D., Calder, P., Fruchart, J.-C., Denefle, P., Auwerx, J. & Staels, B. (1995). Regulation of rat liver apolipoprotein A-I, apolipoprotein A-II and acyl CoA oxidase gene expression by fibrates and dietary fatty acids. European Journal of Biochemistry 232, 179187.Google Scholar
Billiar, T., Bankey, P., Svingen, B., Curran, R. D., West, M. A., Holman, R. T., Simmons, R. L. & Cerra, F. B. (1988). Fatty acid uptake and Kupffer cell function: fish oil alters eicosanoid and monokine production to endotoxin stimulation. Surgery 104, 343349.Google Scholar
Bittiner, S. B., Tucker, W. F. G., Cartwright, I. & Bleehen, S. S. (1988). A double-blind, randomised, placebocontrolled trial of fish oil in psoriasis. Lancet i, 378380.CrossRefGoogle Scholar
Bjorneboe, A., Smith, A. K., Bjorneboe, G.-E. A., Thune, P. O. & Drevon, C. A. (1988). Effect of dietary supplementation with n-3 fatty acids on clinical manifestations of psoriasis. British Journal of Dermatology 118, 7783.Google Scholar
Bjomeboe, A., Soyland, E., Bjomeboe, G.-E. A., Rajka, G. & Drevon, C. A. (1987). Effect of dietary supplementation with eicosapentaenoic acid in the treatment of atopic dermatitis. British Journal of Dermatology 117, 463469.CrossRefGoogle Scholar
Black, J. M. & Kinsella, J. E. (1993). Dietary n-3 fatty acids alter mouse peritoneal macrophage cytotoxicity. Annals of Nutrition and Metabolism 37, 110120.CrossRefGoogle ScholarPubMed
Boutard, V., Fouquery, B., Philippe, C., Perez, J. & Baud, L. (1994). Fish oil supplementation and essential fatty acid deficiency reduce nitric oxide synthesis by rat macrophages. Kidney International 46, 12801286.CrossRefGoogle ScholarPubMed
Breittmayer, J.-P., Pelassy, C., Cousin, J.-L., Bernard, A. & Aussel, C. (1993). The inhibition by fatty acids of receptor-mediated calcium movements in Jurkat T-cells is due to increased calcium extrusion. Journal of Biological Chemistry 268, 2081220817.Google Scholar
Brenner, P. R. (1984). Effect of unsaturated fatty acids on membrane structure and enzymic kinetics. Progress in Lipid Research 23, 6996.Google Scholar
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, 1928.Google Scholar
Brouard, C. & Pascaud, M. (1993). Modulation of rat and human lymphocyte function by n-6 and n-3 polyunsaturated fatty acids and acetylsalicylic acid. Annals of Nutrition and Metabolism 37, 146159.Google Scholar
Calder, P. C. (1995). Fatty acids, dietary lipids and lymphocyte functions. Biochemical Society Transactions 23, 302309.CrossRefGoogle ScholarPubMed
Calder, P. C. (1996 a). Can n-3 polyunsaturated fatty acids be used as immunomodulatory agents? Biochemical Society Transactions 24, 211220.CrossRefGoogle ScholarPubMed
Calder, P. C. (1996 b). Effects of fatty acids and dietary lipids on cells of the immune system. Proceedings of the Nutrition Society 55, 127150.Google Scholar
Calder, P. C., Bevan, S. J. & Newsholme, E. A. (1992). The inhibition of T-lymphocyte proliferation by fatty acids is via an eicosanoid-independent mechanism. Immunology 75, 108115.Google ScholarPubMed
Calder, P. C., Bond, J. A., Bevan, S. J., Hunt, S. V. & Newsholme, E. A. (1991). Effect of fatty acids on the proliferation of concanavalin A-stimulated rat lymph node lymphocytes. International Journal of Biochemistry 23, 579588.Google Scholar
Calder, P. C., Bond, J. A., Harvey, D. J., Gordon, S. & Newsholme, E. A. (1990 c). Uptake of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis. Biochemical Journal 269, 807814.Google Scholar
Calder, P. C., Bond, I. A. & Newsholme, E. A. (1990 a). Fatty acid inhibition of lipopolysaccharide-stimulated B lymphocyte proliferation. Biochemical Society Transactions 18, 904905.Google Scholar
Calder, P. C., Bond, J. A. & Newsholme, E. A. (1990 b). Fatty acid inhibition of concanavalin A-stimulated lymphocyte proliferation. Biochemical Society Transactions 17, 10421043.CrossRefGoogle Scholar
Calder, P. C., Costa-Rosa, L. F. B. P. & Curi, R. (1995). Effects of feeding lipids of different fatty acid compositions upon rat lymphocyte proliferation. Life Sciences 56, 455463.Google Scholar
Calder, P. C. & Newsholme, E. A. (1992 a). Unsaturated fatty acids suppress interleukin-2 production and transferrin receptor expression by concanavalin A-stimulated rat lymphocytes. Mediators of Inflammation 1, 107115.CrossRefGoogle Scholar
Calder, P. C. & Newsholme, E. A. (1992 b). Polyunsaturated fatty acids suppress human peripheral blood lymphocyte proliferation and interleukin-2 production. Clinical Science 82, 695700.CrossRefGoogle ScholarPubMed
Calder, P. C. & Newsholme, E. A. (1993). Influence of antioxidant vitamins on fatty acid inhibition of lymphocyte proliferation. Biochemistry and Molecular Biology International 29, 175183.Google Scholar
Calder, P. C., Sherrington, E. J., Askanazi, J. & Newsholme, E. A. (1994 a). Inhibition of lymphocyte proliferation in vitro by two lipid emulsions with different fatty acid compositions. Clinical Nutrition 13, 6974.CrossRefGoogle ScholarPubMed
Calder, P. C., Yaqoob, P., Harvey, D. J., Watts, A. & Newsholme, E. A. (1994 b). Incorporation of fatty acids by concanavalin A-stimulated lymphocytes and the effect on fatty acid composition and membrane fluidity. Biochemical Journal 300, 509518.Google Scholar
Calder, P. C., Yaqoob, P. & Newsholme, E. A. (1994 c). Triacylglycerol metabolism by lymphocytes and the effect of triacylglycerols on lymphocyte proliferation. Biochemical Journal 298, 605611.Google Scholar
Cathcart, E. S. & Gonnerman, W. A. (1991). Fish oil fatty acids and experimental arthritis. Rheumatoid Disease Clinics of North America 17, 235242.Google Scholar
Cathcart, E. S., Leslie, C. A., Meydani, S. N. & Hayes, K. C. (1987). A fish oil diet retards experimental amyloidosis, modulates lymphocyte function and decreases macrophage arachidonate metabolism in mice. Journal of Immunology 139, 18501854.Google Scholar
Chaet, M. S., Garcia, V. F., Arya, G. & Ziegler, M. M. (1994). Dietary fish oil enhances macrophage production of nitric oxide. Journal of Surgical Research 57, 6568.CrossRefGoogle ScholarPubMed
Chandrasekar, B. & Fernandes, G. (1994). Decreased pro-inflammatory cytokines and increased antioxidant enzyme gene expression by ω-3 lipids in murine lupus nephritis. Biochemical and Biophysical Research Communications 200, 893898.Google Scholar
Chang, H. R., Arsenijevic, D., Pechere, J. C., Piguet, P. F., Mensi, N., Girardier, L. & Dulloo, A. G. (1992 a). Dietary supplementation with fish oil enhances in vivo synthesis of tumor necrosis factor. Immunology Letters 34, 1318.Google Scholar
Chang, H. R., Dulloo, A. G., Vladoianu, I. R., Piguet, P. F., Arsenijevic, D., Girardier, L. & Pechere, J. C. (1992 b). Fish oil decreases natural resistance of mice to infection with Salmonella typhimurium. Metabolism 41, 12.Google Scholar
Chapkin, R. S., Akoh, C. C. & Lewis, R. E. (1992). Dietary fish oil modulation of in vivo peritoneal macrophage leukotriene production and phagocytosis. Journal of Nutritional Biochemistry 3, 599604.CrossRefGoogle Scholar
Chapkin, R. S., Hubbard, N. E. & Erickson, K. L. (1990). 5-Series peptido-leukotriene synthesis in mouse peritoneal macrophages: modulation by dietary n-3 fatty acids. Biochemical and Biophysical Research Communications 171, 764769.Google Scholar
Chen, L. Y., Lawson, D. L. & Mehta, J. L. (1994). Reduction in human neutrophil superoxide anion generation by n-3 polyunsaturated fatty acids: role of cyclooxygenase products and endothelium-derived relaxing factor. Thrombosis Research 76, 317322.Google Scholar
Chow, S. C., Ansotegui, I. J. & Jondal, M. (1990). Inhibition of receptor-mediated calcium influx in T cells by unsaturated non-esterified fatty acids. Biochemical Journal 267, 727732.Google Scholar
Clark, W. F., Parbtani, A., Huff, M. W., Reid, B., Holub, B. J. & Falardeau, P. (1989). Omega-3 fatty acid dietary supplementation in systemic lupus erythematosus. Kidney International 36, 653660.Google Scholar
Cleland, L. G., French, J. K., Betts, W. H., Murphy, G. A. & Elliott, M. J. (1988). Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. Journal of Rheumatology 15, 14711475.Google Scholar
Cooper, A. L., Gibbons, L., Horan, M. A., Little, R. A. & Rothwell, N. J. (1993). Effect of dietary fish oil supplementation on fever and cytokine production in human volunteers. Clinical Nutrition 12, 321328.Google Scholar
Curtain, C. C., Looney, F. D., Marchalonis, J. J. & Raison, J. K. (1978). Changes in lipid ordering and state of aggregation in lymphocyte plasma membranes after exposure to mitogens. Journal of Membrane Biology 44, 211232.CrossRefGoogle ScholarPubMed
D'Ambola, J. B., Aeberhard, E. E., Trang, N., Gaffar, S., Barrett, C. T. & Sherman, M. P. (1991). Effect of dietary (n-3) and (n-6) fatty acids on in vivo pulmonary bacterial clearance by neonatal rabbits. Journal of Nutrition 121, 12621269.CrossRefGoogle ScholarPubMed
Das, U. N. (1994). Beneficial effect of eicosapentaenoic and docosahexaenoic acids in the management of systemic lupus erythematosus and its relationship to the cytokine network. Prostaglandins. Leukotrienes and Essential Fatty Acids 51, 207213.Google Scholar
De Caterina, R., Cybulsky, M. A., Clinton, S. K., Gimbrone, M. A. & Libby, P. (1995). Omega-3 fatty acids and endothelial leukocyte adhesion molecules. Prostaglandins, Leukotrivnes and Es.svntial Fatty Acids 52, 191195.Google Scholar
DeMarco, D. M., Santoli, D. & Zurier, R. B. (1994). Effects of fatty acids on proliferation and activation of human synovial compartment lymphocytes. Journal of Leukocyte Biology 56, 612615.Google Scholar
Devi, M. A. & Das, U. N. (1994). Antiproliferative effect of polyunsaturated fatty acids and interleukin-2 on normal and abnormal human lymphocytes. Experientia 50, 489492.Google Scholar
Dustin, L. B., Shea, C. M., Soberman, R. J. & Lu, C. Y. (1990). Docosahexaenoic acid, a constituent of rodent fetal serum and fish oil diets, inhibits acquisition of macrophage tumoricidal function. Journal of Immunology 14, 48884897.Google Scholar
Dyerberg, J., Bang, H. O. & Hjorne, N. (1975). Fatty acid composition of the plasma lipids in Greenland Eskimos. American Journal of Clinicul Nutrition 28, 958966.Google Scholar
Eicher, S. D. & McVey, D. S. (1995). Dietary modulation of Kupffer cell and splenocyte function during a Salmonella typhimurium challenge in mice. Journal of Leukocyte Biology 58, 3239.Google Scholar
Elzinga, L., Kelley, V. E., Houghton, D. C. & Bennett, W. M. (1987). Modification of experimental nephrotoxicity with fish oil as the vehicle for cyclosporine. Transplantation 43, 271274.Google Scholar
Endres, S., Eisenhut, T. & Sinha, B. (1995). N-3 polyunsaturated fatty acids in the regulation of human cytokine synthesis. Biochemical Society Transactions 23, 277281.Google Scholar
Endres, S., Ghorbani, R., Kelley, V. E., Georgilis, K., Lonnemann, G., van der Meer, J. M. W., Cannon, J. G., Rogers, T. S., Klempner, M. S., Weber, P. C., Schaeffer, E. J., Wolff, S. M. & Dinarello, C. A. (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 England Journal of Medicine 320, 265271.Google Scholar
Endres, S., Meydani, S. N., Ghorbani, R., Schindler, R. & Dinarello, C. A. (1993). Dietary supplementation with n-3 fatty acids suppresses interleukin-2 production and mononuclear cell proliferation. Journal of Leukocyte Biology 54, 599603.Google Scholar
Esperson, G. T., Grunnet, N., Lervang, H. H., Nielsen, G. L., Thomsen, B. S., Faarvang, K. L., Dyerberg, J. & Ernst, E. (1992). Decreased interleukin-1 beta levels in plasma from rheumatoid arthritis patients after dietary supplementation with n-3 polyunsaturated fatty acids. Clinical Rheumatology 11, 393395.CrossRefGoogle Scholar
Feogh, M. L. (1988). Immune regulation by eicosanoids. Transplantation Proceedings 20, 11581161.Google Scholar
Feogh, M. L., Alijani, M. R., Helfrich, G. B., Khirabadi, B. S. & Ramwell, P. W. (1986). Fatty acids and eicosanoids in organ transplantation. Progress in Lipid Research 25, 567572.Google Scholar
Ferber, E., de Pasquale, G. G. & Resch, K. (1975). Phospholipid metabolism of stimulated lymphocytes. Biochimica et Biophysica Acta 398, 364376.Google Scholar
Ferndndes, G., Bysani, C., Venkatraman, J. T., Tomar, V. & Zhao, W. (1994). Increased TGF-β and decreased oncogene expression by ω-3 fatty acids in the spleen delays onset of autoimmune disease in B/W mice. Journal of Immunology 152, 59795987.Google Scholar
Fisher, M., Levine, P. H., Weiner, B. H., Johnson, M. H., Doyle, E. M., Ellis, P. A. & Hoogasian, J. J. (1990). Dietary n-3 fatty acid supplementation reduces superoxide production and chemiluminescence in a monocyte-enriched preparation of leukocytes. American Journal of Clinical Nutrition 51, 804808.Google Scholar
Fletcher, M. P. & Ziboh, V. A. (1990). Effects of dietary supplementation with eicosapentaenoic acid or gammalinolenic acid on neutrophil phospholipid fatty acid composition and activation responses. Inflammation 14, 585597.CrossRefGoogle ScholarPubMed
Fowler, K. H., Chapkin, R. S. & McMurray, D. N. (1993). Effects of purified dietary n-3 ethyl esters on murine Tlymphocyte function. Journal of Immunology 151, 51865197.Google Scholar
Fritsche, K. L., Alexander, D. W., Cassity, N. A. & Huang, S.-C. (1993). Maternally supplied fish oil alters piglet immune cell fatty acid profile and eicosanoid production. Lipids 28, 677682.Google Scholar
Fritsche, K. L. & Cassity, N. A. (1992). Dietary n-3 fatty acids reduce antibody-dependent cell cytotoxicity and alter eicosanoid release by chicken immune cells. Poultry Science 71, 16461657.Google Scholar
Fritsche, K. L., Cassity, N. A. & Huang, S.-C. (1991). Effects of dietary fat source on antibody production and lymphocyte proliferation in chickens. Poultry Science 70, 611617.Google Scholar
Fritsche, K. L. & Johnstone, P. V. (1990). Effects of dietary omega-3 fatty acids on cell-mediated cytotoxic activity in BALB/c mice. Nutrition Research 10, 577588.Google Scholar
Fujikawa, M., Yamashita, N., Yamazaki, K., Sugiyamn, E., Suzuki, H. & Hamazaki, T. (1992). Eicosapentaenoic acid inhibits antigen-presenting cell function of murine splenocytes. Immunology 75, 330335.Google 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, 143153.CrossRefGoogle Scholar
Goldyne, M. E. (1988). Lymphocytes and arachidonic acid metabolism. Progress in Allergy 44, 140152.Google Scholar
Goldyne, M. E. & Stobo, J. D. (1981). Immunoregulatory role of prostaglandins and related lipids. Critical Reviews in Immunology 2, 189223.Google Scholar
Goodwin, J. S. & Cueppens, J. (1983). Regulation of the immune response by prostaglandins. Journal of clinical Immunology 3, 295315.Google Scholar
Grimble, R. F. & Tappia, P. S. (1995). Modulatory influence of unsaturated fatty acids on the biology of tumour necrosis factor-α. Biochemical Society Transactions 23, 282287.Google Scholar
Grimm, H., Tibell, A. & Norrlind, B. (1993). Intravenous fat emulsions rich in omega-3 fatty acids prolong the survival of allotransplants in rats. In Omega-3 Fatty Acids: Metabolism and Biological Eaects, pp. 6976 [Drevon, C. A., Baksaas, I. and Krokan, H. E., editors]. Basel: Brikhauser.Google Scholar
Grimminger, F. & Mayser, P. (1995). Lipid mediators, free fatty acids and psoriasis. Prostaglandins, Leukotrienes and Essential Fatty Acids 52, 115.Google Scholar
Gurr, M. I. (1983). The role of lipids in the regulation of the immune system. Progress in Lipid Research 22, 257287.CrossRefGoogle ScholarPubMed
Hardardottir, I. & Kinsella, J. E. (1991). Tumour necrosis factor production by murine resident peritoneal macrophages is enhanced by dietary n-3 polyunsaturated fatty acids. Biochimica et Biophysica Acta 1095, 187195.CrossRefGoogle ScholarPubMed
Hardardottir, I. & Kinsella, J. E. (1992). Increasing the dietary (n-3) to (n-6) polyunsaturated fatty acid ratio increases tumor necrosis factor production by murine resident peritoneal macrophages without an effect on elicited peritoneal macrophages. Journal of Nutrition 122, 19421951.Google Scholar
Hawthorne, A. B., Daneshmend, T. K., Hawkey, C. J., Belluzzi, A., Everitt, S. J., Holmes, G. K. T., Malkinson, C., Shaheen, M. Z. & Willars, J. E. (1992). Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. Gut 33, 922928.CrossRefGoogle ScholarPubMed
Hellerstein, M. K., Meydani, S. N., Meydani, M., Wu, K. & Dinarello, C. A. (1989). lnterleukin-1-induced anorexia in the rat: Influence of prostaglandins. Journal of Clinical Investigation 84, 228235.Google Scholar
Henderson, M. M. (1991). Correlations between fatty acid intake and cancer incidence. In Health Effects of Dietary Fatty Acids, pp. 136149 [Nelson, G. J., editor]. Champaign: American Oil Chemists' Society.Google Scholar
Hinds, A. & Sanders, T. A. B. (1993). The effect of increasing levels of dietary fish oil rich in eicosapentaenoic and docosahexaenoic acids on lymphocyte phospholipid fatty acid composition and cell-mediated immunity in the mouse. British Journal of Nutrition 69, 423429.Google Scholar
Homan van der Heide, J. J., Bilo, H. J. G., Donker, J. M., Wilmink, J. M. & Tegzess, A. M. (1993). Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants. New England Journal of Medicine 329, 769773.Google Scholar
Huang, S.-C., Misfeldt, M. L. & Fritsche, K. L. (1992). Dietary fat influences la antigen expression and immune cell populations in the murine peritoneum and spleen. Journal of Nutrition 122, 12191231.Google Scholar
Hubbard, N. E., Chapkin, R. S. & Erickson, K. L. (1994). Effect of dietary linseed oil on tumoricidal activity and eicosanoid production in murine macrophages. Lipids 29, 651655.Google Scholar
Hubbard, N. E., Somers, S. D. & Erickson, K. L. (1991). Effect of dietary fish oil on development and selected functions of murine inflammatory macrophages. Journal of Leukocyte Biology 49, 592598.Google Scholar
Huber, L. A., Xu, C.-B., Jurgens, G., Bock, G., Buhler, E., Gey, K. F., Schonitzer, D., Traill, K. N. & Wick, G. (1991). Correlation of lymphocyte lipid composition membrane microviscosity and mitogen response in the aged. European Journal of Immunology 21, 27612765.CrossRefGoogle ScholarPubMed
Hughes, D. A., Pinder, A. C., Piper, Z. & Lund, E. K. (1995). N-3 polyunsaturated fatty acids (PUFA) modulate the expression of functionally associated molecules on human monocytes. Biochemical Society Transactions 23, 303S.Google Scholar
Hwang, D. (1989). Essential fatty acids and the immune response. FASEB Journal 3, 20522061.Google Scholar
Jeffery, N. M., Sanderson, P., Newsholme, E. A. & Calder, P. C. (1996). The effect of varying the omega-6: omega-3 ratio of the diet upon immune function in the rat. Biochemical Society Transactions 24, 77S.Google Scholar
Joe, B. & Lokesh, B. R. (1994). Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochimica et Biophysica Acta 1224, 255263.Google Scholar
Jump, D. B., Ren, B., Clarke, S. & Thelen, A. (1995). Effects of fatty acids on hepatic gene expression. Prostaglandins, Leukotrienes and Essential Fatty Acids 48, 107111.Google Scholar
Kelley, D. S., Branch, L. B., Love, J. E., Taylor, P. C., Rivera, Y. M. & Iacono, J. M. (1991). Dietary alphalinolenic acid and immunocompetence in humans. American Journal of Clinical Nutrition 53, 4046.Google Scholar
Kelley, D. S., Nelson, G.J., Serrato, C. M., Schmidt, P. C. & Branch, L. B. (1988). Effects of type of dietary fat on indices of immune status of rabbits. Journal of Nutrition 118, 13761384.CrossRefGoogle ScholarPubMed
Kelley, V. E., Ferretti, A., Izui, S. & Strom, T. B. (1985). A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites and suppresses lupus in MRL-lpr mice. Journal of Immunology 134, 19141919.Google Scholar
Kelley, V. E., Kirkman, R. L., Bastos, M., Barrett, L. V. & Strom, T. B. (1989). Enhancement of immunosuppression by substitution of fish oil for olive oil as a vehicle for cyclosporine. Transplantation 48, 98102.Google Scholar
Kelly, J. P. & Parker, C. W. (1979). Effect of arachidonic acid and other unsaturated fatty acids on mitogenesis in human lymphocytes. Journal of Immunology 122, 15561562.Google Scholar
Khair-El-Din, T. A., Sicher, S. C., Vazquez, M. A., Wright, W. J. & Lu, C. Y. (1995). Docosahexaenoic acid, a major constituent of fetal serum and fish oil diets, inhibits IFNγ-induced Ia-expression by murine macrophages in vitro. Journal of Immunology 154, 12961306.Google Scholar
Kim, D. M., Schmee, J. & Thomas, W. A. (1995). Dietary fish oil added to a hyperlipidemic diet for swine results in reduction in the excessive number of monocytes attached to the arterial endothelium. Atherosclerosis 81, 209216.Google Scholar
Kinsella, J. E., Lokesh, B., Broughton, S. & Whelan, J. (1990). Dietary polyunsaturated fatty acids and eicosanoids: potential effects on the modulation of inflammatory and immune cells: An overview. Nutrition 6, 2444.Google Scholar
Kishimoto, A., Takai, Y., Mori, T., Kikkawa, U. & Nishizuka, Y. (1980). Activation of calcium and phospholipiddependent protein kinase by diacylglycerol. Its possible relation to phosphatidylinositol turnover. Journal of Biological Chemistry 255, 22732276.Google Scholar
Kort, W. J., de Keijzer, M. H., Hekking-Weijma, I. & Vermeij, M. (1991). Dietary fatty acids and kidney transplantation in the rat. Annals of Nutrition and Metabolism 35, 148157.Google Scholar
Kremer, J. M. (1993). Studies on the effects of omega-3 fatty acids in the treatment of patients with rheumatoid arthritis. In Omega-3 Fatty Acids: Metabolism and Biological Effects, pp. 271283 [Drevon, C. A.. Baksaas, I. and Krokan, H. E., editors]. Basle: Birkhauser.Google Scholar
Kremer, J. M., Bigaouette, J., Michalek, A. V., Timchalk, M. A., Lininger, L., Rynes, R. I., Huyck, C., Zieminski, J. & Bartholomew, L. E. (1985). Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis. Lancet i, 184187.Google Scholar
Kremer, J. M., Jubiz, W., Michalek, A., Rynes, R. I., Bartholomew, L. E., Bigaouette, J., Timchalk, M., Beeler, D. & Lininger, L. (1987). Fish oil fatty acid supplementation in active rheumatoid arthritis. Annals of Internal Medicine 106, 497502.Google Scholar
Kremer, J. M., Lawrence, D. A., Jubiz, W., Di Giacomo, R., Rynes, K., Bartholomew, L. E. & Sherman, M. (1990). Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Arthritis and Rheumatism 33, 810820.Google Scholar
Kromann, N. & Green, A. (1980). Epidemiological studies in the Upernavik District, Greenland. Acta Medica Scandinavica 208, 401406.Google Scholar
Kromhout, D., Bosschieter, E. B. & de Lezenne Coulander, C. (1985). The inverse relationship between fish consumption and 20-year mortality from coronary heart disease. New England Journal of Medicine 312, 12051208.Google Scholar
Kumar, G. S., Das, U. N., Kumar, K. V., Madhavi, N., Das, N. P. & Tan, B. K. H. (1992). Effect of n-6 and n-3 fatty acids on the proliferation of human lymphocytes and their secretion of TNF-alpha and IL-2 in vitro. Nutrition Research 12, 815823.Google Scholar
Kunkel, S. L., Remick, D. G., Spengler, M. & Chensue, S. W. (1982). Modulation of macrophage-derived interleukin-1 and tumor necrosis factor by prostaglandin E2 . Advances in Prostaglandin, Thromboxane and Leukotriene Research 9, 331339.Google Scholar
Leaf, A. & Weber, P. C. (1988). Cardiovascular effects of n-3 fatty acids. New England Journal of Medicine 318, 549557.Google Scholar
Lee, T. H., Hoover, R. L., Williams, J. D., Sperling, R. I., Ravalese, J., Spur, B. W., Robinson, D. R., Corey, E. J., Lewis, R. A. & Austen, K. F. (1985). Effects of dietary enrichment with EPA and DHA on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. New England Journal of Medicine 312, 12171224.Google Scholar
Lefkowith, J. B., Morrison, A., Lee, V. & Rogers, M. (1990). Manipulation of the acute inflammatory response by dietary polyunsaturated fatty acid modulation. Journal of Immunology 145, 15231529.Google Scholar
Lokesh, B. R., Black, J. M., German, J. B. & Kinsella, J. E. (1988). Docosahexaenoic acid and other dietary omega-3 polyunsaturated fatty acids suppress leukotriene synthesis by mouse peritoneal macrophages. Lipids 23, 968972.Google Scholar
Lokesh, B. R., Hsieh, H. L. & Kinsella, J. E. (1986). Peritoneal macrophages from mice fed dietary (n-3) polyunsaturated fatty acids secrete low levels of prostaglandins. Journal of Nutrition 116, 25472552.Google Scholar
Lokesh, B. R., Sayers, T. J. & Kinsella, J. E. (1990). Interleukin-1 and tumor necrosis factor synthesis by mouse peritoneal macrophages is enhanced by dietary n-3 polyunsaturated fatty acids. Immunology Letters 23, 281286.CrossRefGoogle ScholarPubMed
Lumpkin, E. A., McGlone, J. J., Sells, J. L. & Hellman, J. M. (1993). Modulation of murine natural killer cell cytotoxicity by dietary fish oil, corn oil or beef tallow. Journal of Nutritional Immunology 2, 4353.Google Scholar
Maachi, K., Berthoux, P., Burgard, G., Alamartine, E. & Berthoux, F. (1995). Results of a 1-year randomized controlled trial with omega-3 fatty acid fish oil-in renal transplantation under triple immunosuppressive therapy. Transplantation Proceedings 27, 846849.Google Scholar
Maccecchini, M.-L. & Burger, M. M. (1977). Stimulation of lymphocytes by concanavalin A: temperaturedependent effect of fatty acid replacements. Biochimica of Biophysica Acta 469, 3344.Google Scholar
Magrum, L. J. & Johnston, P. V. (1983). Modulation of prostaglandin synthesis in rat peritoneal macrophages with ω-3 fatty acids. Lipids 18, 514521.Google Scholar
Magrum, L. J. & Johnston, P. V. (1985). Effect of culture in vitro with eicosatetraenoic (20:4n-6) and eicosapentaenoic (20:5n-3) acids on fatty acid composition, prostaglandin synthesis and chemiluminescence of rat peritoneal macrophages. Biochimica et Biophysica Acta 836, 354360.Google Scholar
Marshall, L. A. & Johnston, P. V. (1985). The influence of dietary essential fatty acids on rat immunocompetent cell prostaglandin synthesis and mitogen-induced blastogenesis. Journal of Nutrition 115, 15721580.Google Scholar
Mascoli, E. A., Iwasa, Y., Trimbo, S., Leader, L., Bistrian, B. R. & Blackbum, G. L. (1989). Endotoxin challenge after menhaden oil diet: effects on survival of guinea pigs. American Journal of Clinical Nutrition 49, 277282.Google Scholar
Mascoli, E. A., Leader, L., Flores, E., Trimbo, S., Bistrian, B. & Blackburn, G. (1988). Enhanced survival to endotoxin in guinea pigs fed iv fish oil emulsion. Lipids 23, 623625.Google Scholar
Maurice, P. D. L., Allen, B. R., Barkley, A. S. T., Cockbill, S. R., Stammers, J. & Bather, P. C. (1987). The effects of dietary supplementation with fish oil in patients with psoriasis. British Journal of Dermatology 117, 599606.Google Scholar
May, C. L., Southwoth, A. J. & Calder, P. C. (1993). Inhibition of lymphocyte protein kinase C by unsaturated fatty acids. Biochemical and Biophysical Research Communications 195, 823828.Google Scholar
Mayatepek, E., Paul, K., Leichsenring, M., Pfisterer, M., Wagener, D., Domann, M., Sonntag, H. G. & Brener, H. J. (1994). Influence of dietary (n-3) polyunsaturated fatty acids on letikotriene B4 and prostaglandin E2 synthesis and the time course of experimental tuberculosis in guinea pigs. Infection 22, 106112.Google Scholar
Mertin, J. & Meade, C. J. (1977). Relevance of fatty acids to multiple sclerosis. British Medical Bulletin 33, 6771.Google Scholar
Mertin, J., Stackpole, A. & Shumway, S. (1985). Nutrition and immunity: the immunoregulatory effect of n-6 essential fatty acids is mediated through prostaglandin E. International Archives of Allergy and Applied Immunology 17, 390395.Google Scholar
Meydani, S. N. (1992). Modulation of cytokine production by dietary polyunsaturated fatty acids. Proceedings of the Society for Experimental Biology and Medicine 200, 189193.Google Scholar
Meydani, S. N., Endres, S., Woods, M. M., Goldin, B. R., Soo, C., Morrill-Labrode, A., Dinarello, C. & Gorbach, S. L. (1991). Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. Journal of Nutrition 121, 547555.Google Scholar
Meydani, S. N., Lichtenstein, A. H., Cornwall, S., Meydani, M., Goldin, B. R., Rasmussen, H., Dinarello, C. A. & Schaefer, E. J. (1993). Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived n-3 fatty acid enrichment. Journal of Clinical Investigation 92, 105113.Google Scholar
Meydani, S. N., Yogeeswaran, G., Liu, S., Baskar, S. & Meydani, M. (1988). Fish oil and tocopherol-induced changes in natural killer cell-mediated cytotoxicity and PGE2 synthesis in young and old mice. Journal of Nutrition 118, 12451252.Google Scholar
Molvig, J., Pociot, F., Worsaae, H., Wogensen, L. D., Baek, L., Christensen, P., Mandrup-Poulsen, T., Andersen, K., Madsen, P., Dyerberg, J. & Nerup, J. (1991). Dietary supplementation with ω-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, 399410.Google Scholar
Mosquera, J., Rodriguez-Iturbe, B. & Parra, G. (1990). Fish oil dietary supplementation reduces Ia expression in rat and mouse peritoneal macrophages. Clinical Immunology and Immunoparhology 56, 124129.Google Scholar
Mulrooney, H. M. & Grimible, R. F. (1993). Influence of butter and of corn, coconut and fish oils on the effects of recombinant human tumour necrosis factor-α in rats. Clinical Science 84, 105112.Google Scholar
Murphy, M. G. (1990). Dietary fatty acids and membrane protein function. Journal of Nutritional Biochemistry 1, 6879.Google Scholar
Nakamura, N., Hamamki, T., Kobayashi, M. & Yazawa, K. (1994). The effect of oral administration of eicosapentaenoic and docosahexaenoic acids on acute inflammation and fatty acid composition in rats. Journal of Nutritional Science and Vitaminology 40, 161170.Google Scholar
Nettleton, J. A.. (editor) (1995). Omega-3 fatty acids in other diseases. In Omega-3 Fatty Acids and Health, pp. 287354. New York: Chapman & Hall.Google Scholar
Nunez, E. A. (1995). Free fatty acids as modulators of the steroid hormone message. Prostaglandins, Leukotrienes and Essential Fatty Acids 48, 6370.Google Scholar
Otto, D. A., Kahn, D. R., Hamm, M. W., Forrest, D. E. & Wooten, J. T. (1990). Improved survival of heterotopic cardiac allografts in rats with dietary n-3 polyunsaturated fatty acids. Transplantation 50, 193198.Google Scholar
Parm, J., Horton, C. E., Menica-Huerta, J. M., House, F., Eiser, N. M., Clark, T. S. H., Spur, B. W. & Lee, T. H. (1988). Effect of dietary supplementation with fish oil lipids in mild asthma. Thorax 43, 8492.Google Scholar
Picado, C., Castillo, J. A., Schinca, N., Pujades, M., Ordinas, A., Coronas, A. & Augusti-Vidal, A. (1988). Effccts of tish oil enriched diet on aspirin-tolerant asthmatic patients: a pilot study. Thorax 43, 9397.Google Scholar
Pomposelli, J., Mascioli, E. A., Bistrian, B. R. & Flores, S. M. (1990). Attenuation of the febrile response in guinea pigs by fish oil enriched diets. Journal of Parenteral and Enteral Nutrition 13, 136140.Google Scholar
Poulos, A., Robinson, B. S., Ferrante, A., Harvey, D. P., Hardy, S. J. & Murray, A. W. (1991). Effect of 22–32 carbon n-3 polyunsaturated fatty acids on superoxide production in human neutrophils: synergism of docosahexaenoic acid with f-met-leu-phe and phorbol ester. Immunology 73, 102108.Google Scholar
Prickett, J. D., Robinson, D. R. & Bloch, K. J. (1982). Enhanced production of IgE and IgG antibodies associated with a diet enriched in eicosapentaenoic acid. Immunology 46, 819826.Google ScholarPubMed
Prickett, J. D., Robinson, D. R. & Steinberg, A. D. (1983). Effects of dietary enrichment with eicosapentaenoic acid upon autoimmune nephritis in female NZB 5 NZW/F1 mice. Arthritis and Rheumatism 26, 133139.Google Scholar
Prickett, J. D., Trentham, D. E. & Robinson, D. R. (1984). Dietary fish oil augments the induction of arthritis in rats immunized with type II collagen. Journal of Immunology 132, 725729.Google Scholar
Reddy, A. C. B. & Lokesh, B. R. (1994). Studies on anti-inflammatory activity of spice principles and dietary n-3 polyunsaturated fatty acids on carrageenan-induced inflammation in rats. Annals of Nutrition and Metabolism 38, 349358.Google Scholar
Reddy, B. S. (1991). Omega-3 fatty acids as anticancer agents. In Health Effects of Dietary Fatty Acids, pp. 157166 [Nelson, G. J., editor]. Champaign: American Oil Chemists' Society.Google 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, 15151524.Google Scholar
Resch, K. & Ferber, E. (1972). Phospholipid metabolism of stimulated lymphocytes. European Journal of Biochemistry 27, 153161.Google Scholar
Resch, K., Ferber, E., Odenthal, J. & Fischer, H. (1971). Early changes in the phospholipid metabolism of lymphocytes following stimulation with phytohaemagglutinin and with lysolecithin. European Journal of Immunology 1, 162165.Google Scholar
Resch, K., Gelfrand, E. W., Hansen, K. & Ferber, E. (1972). Lymphocyte activation: rapid changes in the phospholipid metabolism of plasma membranes during stimulation. European Journal of Immunology 2, 598601.Google Scholar
Richieri, G. V. & Kleinfeld, A. M. (1989). Free fatty acid perturbation of transmembrane signalling in cytotoxic T lymphocytes. Journal of Immunology 143, 23022310.Google Scholar
Richieri, G. V. & Kleinfeld, A. M. (1990). Free fatty acids inhibit cytotoxic T lymphocyte-mediated lysis of allogeneic target cells. Journal of Immunology 145, 10741077.Google Scholar
Richieri, G. V., Mescher, M. F. & Kleinfeld, A. M. (1990). Short term exposure to cis unsaturated free fatty acids inhibits degranulation of cytotoxic T lymphocytes. Journal of Immunology 144, 671677.Google Scholar
Robinson, D. R., Knoell, C. T., Urakaze, M., Huang, R., Taki, H., Sugiyama, E., Xu, L.-L., Yeh, E. T. H., Olesiak, W., Guo, M., Colvin, R. B. & Auron, P. E. (1995). Suppression of autoimmune disease by ω-3 fatty acids. Biochemicul Society Transactions 23, 287291.Google Scholar
Robinson, D. R., Prickett, J. D., Makoul, G. T., Steinberg, A. D. & Colvin, R. B. (1986). Dietary fish oil reduces progression of established renal disease in (NZB 5 NZW)F1 mice and delays renal disease in BXSB and MRL/I strains. Arthritis and Rheumatism 29, 539546.Google Scholar
Robinson, D. R., Prickett, J. D., Polisson, R., Steinberg, A. D. & Levine, L. (1985). The protective effect of dietary fish oil on murine lupus. Prostaglandins 30, 5175.Google Scholar
Robinson, D. R., Xu, L., Koell, C., Tateno, S. & Olesiak, W. (1993 a). Modification of spleen phospholipid fatty acid composition by dietary fish oil and by n-3 fatty acid ethyl esters. Journal of Lipid Research 34, 14231434.Google Scholar
Robinson, D. R., Xu, L., Tateno, S., Guo, M. & Colvin, R. B. (1993 b). Suppression of autoimmune disease by dietary n-3 fatty acids. Journal of Lipid Research 34, 14351444.Google Scholar
Rola-Pleszczynski, M., Gagnon, L. & Sirois, P. (1983). Leukotriene B4 augments human natural cytotoxic cell activity. Biochemical and Biophysical Research Communications 113, 531537.Google Scholar
Ross, R. (1993). The pathogenesis of atherosclerosis: a perspective for the 1990s. Nuture 362, 801809.Google Scholar
Rotondo, D., Earl, C. R. A., Laing, K. J. & Kaimakamis, D. (1994). Inhibition of cytokine-stimulated thymic lymphocyte proliferation by fatty acids: the role of eicosanoids. Biochimica et Biophysica Acta 1223, 185194.Google Scholar
Sanderson, P., Yaqoob, P. & Calder, P. C. (1995 a). Effects of dietary lipid manipulation upon rat spleen lymphocyte functions and the expression of lymphocyte surface molecules. Journal of Nutritional and Environmental Medicine 5, 119132.Google Scholar
Sanderson, P., Yaqoob, P. & Calder, P. C. (1995 b). Effects of dietary lipid manipulation upon graft vs. host and host vs. graft responses in the rat. Cellular Immunology 164, 240247.Google Scholar
Santoli, D., Phillips, P. D., Colt, T. L. & Zurier, R. B. (1990). Suppression of interleukin-2-dependent human T cell growth in vitro by prostaglandin E (PGE) and their precursor fatty acids. Journal of Clinical Investigation 85, 424432.Google Scholar
Schmidt, E. B., Pedersen, J. O., Ekelund, S., Grunnet, N., Jersild, C. & Dyerberg, J. (1989). Cod liver oil inhibits neutrophil and monocyte chemotaxis in healthy males. Atherosclerosis 77, 5357.Google Scholar
Schmidt, E. B., Varming, K., Pedersen, J. O., Lervang, H. H., Grunnet, N., Jersild, C. & Dyerberg, J. (1992). Long term supplementation with n-3 fatty acids. II. Effect on neutrophil and monocyte chemotaxis. Scandinavian Journal of Clinical and Laboratory Investigation 52, 229236.Google Scholar
Sherrington, E. J., Harvey, D. I. & Calder, P. C. (1995 a). The effect of dietary lipid manipulation on macrophage phospholipid fatty acid composition and membrane fluidity. Proceedings of the Nutrition Society 54, 121A.Google Scholar
Sherrington, E. J., Sanderson, P. & Calder, P. C. (1995 b). The effect of dietary lipid manipulation on macrophage cell surface molecule expression. Biochemical Society Transactions 23, 272S.Google Scholar
Shinomura, T., Asoaka, Y., Oka, M., Yoshida, K. & Nishizuka, Y. (1991). Synergistic action of diacylglycerol and unsaturated fatty acids for protein kinase C activation. Proceedings of the National Academy of sciences, USA 88, 51495153.Google Scholar
Somers, S. D., Chapkin, R. S. & Erickson, K. L. (1989). Alteration of in vitro murine peritoneal macrophage function by dietary enrichment with eicosapentaenoic and docosahexaenoic acids in menhaden fish oil. Cellular Immunology 123, 201211.Google Scholar
Somers, S. D. & Erickson, K. L. (1994). Alteration of tumor necrosis factor-α production by macrophages from mice fed diets high in eicosapentaenoic and docosahexaenoic acids. Cellular Immunology 153, 287297.Google Scholar
Soyland, E. & Drevon, C. A. (1993). The effect of very long-chain n-3 fatty acids on immune-related skin diseases. European Journal of Clinical Nutrition 47, 381388.Google ScholarPubMed
Soyland, E., Funk, J., Rajka, G., Sandberg, M., Thune, P., Rustad, L., Helland, S., Middelfart, K., Odu, S., Falk, E. S., Solvoll, K., Bjorneboe, G.-E. & Drevon, C. A. (1993 a). Effect of dietary supplementation with very-long-chain n-3 fatty acids in patients with psoriasis. New England Journal of Medicine 328, 18121816.Google Scholar
Soyland, E., Lea, T., Sandstad, B. & Drevon, A. (1994). Dietary supplementation with very long chain n-3 fatty acids in man decreases expression of the interleukin-2 receptor (CD25) on mitogen-stimulated lymphocytes from patients with inflammatory skin diseases. European Journal of Clinical Investigation 24, 236242.Google Scholar
Soyland, E., Nenseter, M. S., Braathen, L. & Drevon, C. A. (1993 b). Very long chain n-3 and n-6 polyunsaturated fatty acids inhibit proliferation of human T lymphocytes in vitro. European Journal of Clinical Investigation 23, 112121.Google Scholar
Speizer, L. A., Watson, M. J. & Brunton, L. L. (1991). Differential effects of omega-3 fish oils on protein kinase activities in vitro. American Journal of physiology 261, E109E114.Google Scholar
Sperling, R. I., Benincaso, A. I., Knoell, C. T., Larkin, J. K., Austen, K. F. & Robinson, D. R. (1993). Dietary ω-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. Journal of Clinical Investigation 91, 651660.Google Scholar
Sperling, R. I., Weinblatt, M. E., Robin, J. L., Ravalese, J., Hoover, R. L., House, F., Coblyn, J. S., Fraser, P. A., Spur, B. W., Robinson, D. R., Lewis, R. A. & Austen, K. F. (1987). Effects of dietary supplementation with marine fish oil on leukocyte lipid mediator generation and function in rheumatoid arthritis. Arthritis and Rheumatism 30, 987988.Google Scholar
Stubbs, C. D. & Smith, A. D. (1984). The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochimica et Biophysica Acta 779, 89137.Google Scholar
Sumida, C. (1995). Fatty acids: Ancestral Iigands and modem co-regulators of the steroid hoimone receptor cell signalling pathway. Prostaglandins, Leukotrienes and Essential Fatty Acids 52, 137144.Google Scholar
Sumida, C., Graber, R. & Nunez, E. (1993). Role of fatty acids in signal transduction: modulators and messengers. Prostaglandins, Leukotrienes and Essential Fatty Acids 48, 117122.Google Scholar
Surette, M. E., Whelan, J., Lu, G., Hardardottir, I. & Kinsella, J. E. (1995). Dietary n-3 polyunsaturated fatty acids modify Syrian hamster platelet and macrophage phospholipid fatty acyl composition and eicosanoid synthesis: a controlled study. Biochimica et Biophysica Acta 122, 185191.Google Scholar
Swank, R. L. (1950). Multiple sclerosis. A correlation of its incidence with dietary fat. American Journal of Medical Science 220, 421430.Google Scholar
Taki, H., Morinaga, S.-I., 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, 511514.Google Scholar
Tappia, P. S. & Grimble, R. F. (1994). Complex modulation of cytokine induction by endotoxin and tumour necrosis factor from peritoneal macrophages of rats by diets containing fats of different saturated, monounsaturated and polyunsaturated fatty acid composition. Clinical Science 87, 173178.Google Scholar
Tappia, P. S., Man, W. J. & Grimble, R. F. (1995). Influence of unsaturated fatty acids on the production of tumour necrosis factor and interleukin-6 by rat peritoneal macrophages. Molecular and Cellular Biochemistry 143, 8998.CrossRefGoogle ScholarPubMed
Taylor, A. S., Howe, R. C., Morrison, A. R., Sprecher, H. & Russell, J. H. (1985). Inhibition of cytotoxic T lymphocyte-mediated lysis by ETYA: effect independent of arachidonic acid metabolism. Journal of Immunology 134, 1139011395.Google Scholar
Terano, T., Kojima, T., Seya, A., Tanabe, E., Hirai, A., Makuda, H., Ozawa, A., Fujita, T., Tamura, Y., Okamoto, S. & Yoshida, S. (1989). The effect of highly purified eicosapentaenoic acid in patients with psoriasis. Advances in Prostaglandin, Thromboxane and Leukotriene Research 19, 610–413.Google Scholar
Thompson, P. J., Misso, N. L. A., Passarelli, M. & Phillips, M. J. (1991). The effect of eicosapentaenoic acid consumption on human neutrophil chemiluminescence. Lipids 26, 12231226.Google Scholar
Turek, J. J., Schoenlein, I. A. & Bottoms, G. D. (1991). The effect of dietary n-3 and n-6 fatty acids on tumor necrosis factor-α production and leucine aminopeptidase levels in rat peritoneal macrophages. Prostaglandins, Leukotrienes and Essential Fatty Acids 43, 141149.Google Scholar
Turek, J. J., Schoenlein, I. A., Clark, L. K. & van Alstine, W. G. (1994). Dietary polyunsaturated fatty acids effects on immune cells of the porcine lung. Journal of Leukocyte Biology 56, 599604.Google Scholar
Twisk, A. J. T., Detering, F. & Kraal, G. (1991). The fatty acid composition of the lymphocyte cell membrane: influence on interactions with high endothelium and the expression of homing receptors. Immunology 183, 386395.Google Scholar
van der Tempel, H., Tulleken, J. E., Limburg, P. C., Muskiet, F. A. J. & van Rijswijk, M. K. (1990). Effects of fish oil supplementation in rheumatoid arthritis. Annals of Rheumatoid Disease 49, 7680.Google Scholar
Van Meter, A. R., Ehringer, W. D., Stillwell, W., Blumenthal, E. J. & Jenski, L. J. (1994). Aged lymphocyte proliferation following incorporation and retention of dietary omega-3 fatty acids. Mechanisms of Ageing and Development 75, 95114.Google Scholar
Vilaseca, J., Salas, A., Guarner, F., Rodriguez, R., Martinez, M. & Malagelada, J.-R. (1990). Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis. Gut 31, 539544.Google Scholar
Virella, G., Fourspring, K., Hyman, B., Haskill-Stroud, R., Long, L., Virella, I., La Via, M., Gross, A. J. & Lopes-Virella, M. (1991). Immunosuppressive effects of fish oil in normal human volunteers: Correlation with the in vitro effects of eicosapentaenoic acid on human lymphocytes. Clinical Immunology and Immunopathology 61, 161176.Google Scholar
Virella, G., Kilpatrick, J. M., Rugeles, M. T., Hyman, B. & Russell, R. (1989). Depression of humoural responses and phagocytic functions in vivo and in vitro by fish oil and eicosapentaenoic acid. Clinical Immunctlogy and Immunpathology 52, 277–270.Google Scholar
Wallace, J. L., Keenan, C. M. & Finn, N. J. (1989). Anti-inflammatory effects of a fish oil diet in a rat model of chronic colitis. Gastroenterology 96, A535.Google Scholar
Watanabe, S., Hayashi, H., Onozaki, K. & Okuyama, H. (1991). Effect of dietary α-linolenate/linoleate balance on lipopolysaccharide-induced tumor necrosis factor production in mouse macrophages. Life Sciences 48, 20132020.Google Scholar
Watson, J., Madhok, R., Wijelath, E., Capell, H. A., Gillespie, J., Smith, J. & Byars, B. L. (1990). Mechanism of action of polyunsaturated fatty acids in rheumatoid arthritis. Biochemical Society Transactions 18, 284285.Google Scholar
Westberg, G. & Tarkowski, A. (1990). Effect of MaxEPA in patients with SLE. Scandinavian Journal of Rheumatology 19, 137143.Google Scholar
Wick, G., Schett, G., Amberger, A., Kleindienst, R. & Xu, Q. (1995). Is atherosclerosis an immunologically mediated disease? Immunology Today 16, 2733.Google Scholar
Yamashita, N., Maruyama, M., Yamazaki, K., Hamazaki, T. & Yano, S. (1991). Effect of eicosapentaenoic and docosahexaenoic acid on natural killer cell activity in human peripheral blood lymphocytes. Clinical Immunology and Immunopathology 59, 335345.Google Scholar
Yamashita, N., Yokoyama, A., Hamazalu, T. & Yano, S. (1986). Inhibition of natural killer cell activity of human lymphocytes by eicosapentaenoic acid. Biochemical and Biophysical Research Communications 138, 10581067.Google Scholar
Yaqoob, P. (1993). The effects of fatty acids on the composition and functions of lymphocytes. DPhil Thesis, University of Oxford.Google Scholar
Yaqoob, P. & Calder, P. C. (1993). The effects of fatty acids on lymphocyte functions. Internationul Journal of Biochemistry 25, 17051714.Google Scholar
Yaqoob, P. & Calder, P. C. (1995 a). The effects of dietary lipid manipulation on the production of murine T-cellderived cytokines. Cytokine 7, 548553.Google Scholar
Yaqoob, P. & Calder, P. C. (1995 b). Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. Cellular Immunology 163, 120128.Google Scholar
Yaqoob, P., Newsholme, E. A. & Calder, P. C. (1994 a). The effect of dietary lipid manipulation on rat lymphocyte subsets and proliferation. Immunology 82, 603610.Google Scholar
Yaqoob, P., Newsholme, E. A. & Calder, P. C. (1994 b). Inhibition of natural killer cell activity by dietary lipids. Immunology Letters 41, 241247.Google Scholar
Yaqoob, P., Newsholme, E. A. & Calder, P. C. (1995 a). The effect of dietary lipid manipulation on leucocyte proliferation in whole blood. Nutrition Research 15, 279287.Google Scholar
Yaqoob, P., Newsholme, E. A. & Calder, P. C. (1995 b). Influence of cell culture conditions on diet-induced changes in lymphocyte fatty acid composition. Biochimica et Biophysica Acta 1255, 333340.Google Scholar
Yoshino, S. & Ellis, E. F. (1987). Effect of a fish oil-supplemented diet on inflammation and immunological processes in rats. International Archives in Allergy and Applied Immunology 84, 233240.Google Scholar
Ziboh, V. A., Cohen, K. A., Ellis, C. N., Miller, C., Hamilton, T. A., Kragballe, K., Hydrick, C. R. & Voorhees, J. J. (1986). Effects of dietary supplementation of fish oil on neutrophil and epidermal fatty acids: modulation of clinical course of psoriatic lesions. Archives of Dermatology 122, 12771282.Google Scholar