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Dietary fatty acid modulation of mucosally-induced tolerogenic immune responses

Published online by Cambridge University Press:  28 February 2007

Laurence S. Harbige  and
Benjamin A. C. Fisher
Laurence S. Harbige*
Affiliation:
School of Chemical and Life Sciences, University of Greenwich, Wellington Street, London SE18 6PF, UK
Benjamin A. C. Fisher
Affiliation:
School of Chemical and Life Sciences, University of Greenwich, Wellington Street, London SE18 6PF, UK
*
*Corresponding Author: Dr L. S. Harbige, fax +44 20 8331 8305, email L.Harbige@gre.ac.uk
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Abstract

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Immunological unresponsiveness or hyporesponsiveness (tolerance) can be induced by feeding protein antigens to naïve animals. Using a classical oral ovalbumin gut-induced tolerance protocol in BALB/c mice we investigated the effects of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on high-and low-dose oral tolerance (and in non-tolerised animals, i.e. effects of antigen challenge alone) in relation to lymphoproliferative, cytokine and antibody responses. Fish oil rich in long-chain n-3 fatty acids decreased both T-helper (Th) 1- and Th2-like responses. In contrast, borage (Borago officinalis) oil rich in n-6 PUFA, of which γ-linolenic acid is rapidly metabolised to longer-chain n-6 PUFA, increased Th1-like responses and decreased Th2-like responses, and possibly enhanced suppressor cell or Th3-like activity. These findings are in general agreement with other studies on the effects of long chain n-3 PUFA on immune system functions, and characterise important differences between long-chain n-3 and n-6 PUFA, defining more precisely and broadly the immunological regulatory mechanisms involved. They are also discussed in relation to autoimmune disease.

Keywords

Dietary n-3 and n-6 fatty acidsCytokine and antibody responsesTolerogenic and antigenic immune responses
Type
Symposium on ‘Dietary influences on mucosal immunity’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 4 , November 2001 , pp. 449 - 456
Copyright
Copyright © The Nutrition Society 2001

References

Adda, DH, Beraud, E & Depieds, R (1977) Evidence for suppressor cells in Lewis rats' experimental allergic encephalomyelitis. European Journal of Immunology 7, 620–623.CrossRefGoogle ScholarPubMed
Avula, CP, Zaman, AK, Lawrence, R & Fernandes, G (1999) Induction of apoptosis and apoptotic mediators in Balb/C splenic lymphocytes by dietary n-3 and n-6 fatty acids. Lipids 34, 921–927.CrossRefGoogle ScholarPubMed
Bailey, M, Plunkett, FJ, Rothkotter, HJ, Vega-Lopez, MA, Haverson, K & Stokes, CR (2001) Regulation of mucosal immune responses in effector sites. Proceedings of the Nutrition Society 60, 427–435.CrossRefGoogle ScholarPubMed
Barker, DJ (1998) In utero programming of chronic disease. Clinical Science 95, 115–128.CrossRefGoogle ScholarPubMed
Barone, KS, Tolarova, DD, Ormsby, I, Doetschman, T & Michael, JB (1998) Induction of oral tolerance in TGF-β1 null mice. Journal of Immunology 161, 154–160.CrossRefGoogle Scholar
Benson, JM & Whitacre, CL (1997) The role of clonal deletion and anergy in oral tolerance. Research in Immunology 148, 533–541.CrossRefGoogle ScholarPubMed
Betz, M & Fox, BS (1991) Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. Journal of Immunology 146, 108–113.CrossRefGoogle Scholar
Burstein, HJ & Abbas, AK (1993) In vivo role of interleukin 4 in T cell tolerance induced by aqueous protein antigen. Journal of Experimental Medicine 177, 457–463.CrossRefGoogle Scholar
Buttke, TM & Sandstrom, PA (1994) Oxidative stress as a mediator of apoptosis. Immunology Today 15, 7–10.CrossRefGoogle ScholarPubMed
Calder, PC (1996) Immunomodulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids. Proceedings of the Nutrition Society 55, 737–774.CrossRefGoogle ScholarPubMed
Calder, PC (1998) Dietary fatty acids and lymphocyte functions. Proceedings of the Nutrition Society 57, 487–502.CrossRefGoogle ScholarPubMed
Chang, HR, Dulloo, AG, Vladoianu, IR, Piguet, PF, Arsenijevic, D, Girardier, L & Pechere, JC (1992) Fish oil decreases natural resistance of mice to infection with Salmonella typhimurium. Metabolism 41, 1–2.CrossRefGoogle ScholarPubMed
Chin, J, Turner, B, Barchia, I & Mullbacher, A (2000) Immune response to orally consumed antigens and probiotic bacteria. Immunology and Cell Biology 78, 55–66.CrossRefGoogle ScholarPubMed
Cinader, B, Clandinin, MT, Hosokawa, T & Robblee, NM (1983) Dietary fat alters the fatty acid composition of lymphocyte membranes and the rate at which suppressor capacity is lost. Immunology Letters 6, 331–337.CrossRefGoogle ScholarPubMed
Clausen, J & Moller, J (1967) Allergic encephalomyelitis induced by brain antigen after deficiency in polyunsaturated fatty acids during myelination. Acta Neurologica Scandinavica 43, 375–388.CrossRefGoogle ScholarPubMed
Crawford, MA (1983) Background to essential fatty acids and their prostanoid derivatives. British Medical Bulletin 39, 210–213.CrossRefGoogle ScholarPubMed
Crawford, MA, Costeloe, K, Ghebremeskel, K, Phylactos, A, Skirvin, L & Stacey, F (1997) Are deficits of arachidonic and docosahexaenoic acids responsible for neural and vascular complications of preterm babies? American Journal of Clinical Nutrition 66 Suppl., 1032S–1041S.CrossRefGoogle ScholarPubMed
de Pablo, MA and Alvarez de Cienfuegos, (2000) Modulatory effects of dietary lipids on immune system functions. Immunology and Cell Biology 78, 31–39.CrossRefGoogle ScholarPubMed
Drury, PJ & Crawford, MA (1990) Essential fatty acids in human milk. In. Clinical Nutrition of the Young Child, vol. 2, pp. 289–312 [Ballabring, A, Brunser, O, Dobbing, J, Gracey, M and Senterre, J, editors]. New York: Nestec Ltd, Raven Press Ltd.Google Scholar
Dvorak, B & Stepankova, R (1992) Effects of dietary essential fatty acid deficiency on the development of the rat thymus and immune system. Prostaglandins Leukotrienes and Essential Fatty Acids 46, 183–190.CrossRefGoogle ScholarPubMed
Fernandes, G, Chandrasekar, B, Luan, X & Troyer, DA (1996) Modulation of antioxidant enzymes and programmed cell death by n-3 fatty acids. Lipids 31, Suppl., S91–S96.CrossRefGoogle ScholarPubMed
Forsthuber, T, Yip, HC & Lehmann, PV (1996) Induction of TH1 and TH2 immunity in neonatal mice. Science 271, 1728–1730.CrossRefGoogle ScholarPubMed
Friedman, A & Weiner, HL (1994) Induction of anergy or active suppression following oral tolerance is determined by antigen dosage. Proceedings of the National Academy of Sciences USA 91, 6688–6692.CrossRefGoogle ScholarPubMed
Fujikawa, M, Yamashita, N, Yamazaki, K, Sugiyama, E, Suzuki, H & Hamazaki, T (1992) Eicosapentaenoic acid inhibits antigen-presenting cell function of murine splenocytes. Immunology 75, 330–335.Google ScholarPubMed
Garside, P, Steel, M, Liew, FY & Mowat, AM (1995 a) CD4+ but not CD8+ T cells are required for the induction of oral tolerance. International Immunology 7, 505–504.CrossRefGoogle Scholar
Garside, P, Steel, M, Worthey, EA, Satoskar, A, Alexander, J, Bluethmann, H, Liew, FY & Mowat, AM (1995 b) T helper 2 cells are subject to high dose oral tolerance and are not essential for its induction. Journal of Immunology 154, 5649–5655.CrossRefGoogle Scholar
Grimm, H, Grimminger, F, Korom, S & Seeger, W (1998) Use of fish oil to prevent graft rejection. Proceedings of the Nutrition Society 57, 577–585.CrossRefGoogle ScholarPubMed
Goodwin, JS & Webb, DR (1981) Regulation of the immune response by prostaglandins. Clinical Immunology and Immunopathology 15, 106–122.CrossRefGoogle Scholar
Goetzl, EJ, An, S & Smith, WL (1995) Specificity of expression and effects of eicosanoid mediators in normal physiology and human disease. FASEB Journal 9, 1051–1058.CrossRefGoogle Scholar
Goldyne, ME & Stobo, JD (1981) Immunoregulatory role of prostaglandins and related lipids. CRC Critical Reviews in Immunology 2, 189–223.Google Scholar
Harbige, LS (1993) Essential fatty acids, experimental autoimmune encephalomyelitis and multiple sclerosis. PhD Thesis, Brunel University.Google Scholar
Harbige, LS (1998) Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease. Proceedings of the Nutrition Society 57, 555–562.CrossRefGoogle ScholarPubMed
Harbige, LS, Ghebremeskel, K, Williams, G & Summers, P (1990) N-3 and N-6 phosphoglyceride fatty acids in relation to hydrogen peroxide induced in vitro erythrocyte haemolysis in captive marmosets (Callithrix jacchus). Comparative Biochemistry and Physiology 97B, 167–170.Google Scholar
Harbige, LS, Layward, L, Morris-Downes, MM, Dumonde, DC & Amor, S (2000) The protective effects of omega-6 fatty acids in experimental autoimmune encephalomyelitis (EAE) in relation to transforming growth factor-beta 1 (TGF-β1) up-regulation and increased prostaglandin E2 (PGE2) production. Clinical and Experimental Immunology 122, 445–452.CrossRefGoogle ScholarPubMed
Harbige, LS, Yeatman, N, Amor, S & Crawford, MA (1995) Prevention of experimental autoimmune encephalomyelitis in Lewis rats by a novel source of γ-linolenic acid. British Journal of Nutrition 74, 701–715.CrossRefGoogle ScholarPubMed
Heyman, M (2001) How dietary antigens access the mucosal immune system. Proceedings of the Nutrition Society 60, 419–426.CrossRefGoogle ScholarPubMed
Hopkins, J, McConnell, I & Pearson, JD (1981) Lymphocyte traffic through antigen-stimulated lymph nodes II: role of prostaglandin E2 as a mediator of cell shutdown. Immunology 42, 225–231.Google ScholarPubMed
Hughes, DA (1998) In vitro and in vivo effects of n-3 polyunsaturated fatty acids on human monocyte function. Proceedings of the Nutrition Society 57, 521–525.CrossRefGoogle ScholarPubMed
Isolauri, E, Sutas, Y, Kankaanpaa, P Arvilommi, H, & Salminen, S (2001) Probiotics: effects on immunity. American Journal of Clinical Nutrition 73, Suppl., 444S–450S.CrossRefGoogle ScholarPubMed
Jarocka-Cyrta, E, Perin, N, Keelan, M, Wierzbicki, E, Wierzbicki, T, Clandinin, MT & Thomson, ABR (1998) Early dietary experience influences ontogeny of intestine in response to dietary lipid changes in later life. American Journal of Physiology 275, G250–G258.Google ScholarPubMed
Karpus, WJ & Swanborg, RH (1991) CD4+ suppressor cells inhibit the function of effector cells of experimental autoimmune encephalomyelitis through a mechanism involving transforming growth factor-β. Journal of Immunology 146, 1163–1168.CrossRefGoogle ScholarPubMed
Kolb, H & Pozzilli, P (1999) Cow's milk and type I diabetes: the gut immune system deserves attention. Immunology Today 20, 108–110.CrossRefGoogle ScholarPubMed
Lamont, AG, Mowat, AM, Browning, MJ & Parrott, DMV (1988) Genetic control of oral tolerance to ovalbumin in mice. Immunology 63, 737–739.Google ScholarPubMed
Matsuzaki, T & Chin, D (2000) Modulating immune responses with probiotic bacteria. Immunology and Cell Biology 78, 67–73.CrossRefGoogle ScholarPubMed
Meade, JF (1981) The essential fatty acids: past, present and future. Progress in Lipid Research 20, 1–6.CrossRefGoogle Scholar
Melamed, D & Friedman, A (1993) Direct evidence for anergy in T lymphocytes tolerized by oral administration of ovalbumin. European Journal of Immunology 23, 935–942.CrossRefGoogle Scholar
Mertin, J (1983) Omega-6 and omega-3 polyunsaturates and the immune system. British Journal of Clinical Practice 31, Suppl., 111–114.Google Scholar
Mohajer, B & Ma, TY (2000) Eicosanoids and the small intestine. Prostaglandins and Other Lipid Mediators 61, 125–143.CrossRefGoogle ScholarPubMed
Mosman, TR & Coffman, RL (1989) Th1 and Th2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology 7, 145–173.CrossRefGoogle Scholar
Mosman, TR & Sad, S (1996) The expanding universe of T cell subsets: Th1, Th2 and more. Immunology Today 17, 138–146.CrossRefGoogle Scholar
Mowat, AM, Strobel, S, Drummond, HE & Ferguson, A (1982) Immunological responses to fed protein antigens in mice. 1. Reversal of oral tolerance to ovalbumin by cyclophosphamide. Immunology 45, 105–113.Google ScholarPubMed
Nagler-Anderson, C (2000) Tolerance and immunity in the intestinal immune system. Critical Reviews in Immunology 20, 103–120.Google ScholarPubMed
Phipps, RP, Stein, SH & Roper, RL (1991) A new view of prostaglandin E regulation of the immune response. Immunology Today 12, 349–352.CrossRefGoogle ScholarPubMed
Ridge, JP, Fuchs, EJ & Matzinger, P (1996) Neonatal tolerance revisited: turning on newborn T cells with dendritic cells. Science 271, 1723–1726.CrossRefGoogle ScholarPubMed
Rivers, JPW & Frankel, TL (1981) Essential fatty acid deficiency. British Medical Bulletin 37, 59–64.CrossRefGoogle ScholarPubMed
Roper, LR, Conrad, DH, Brown, DM, Warner, GL & Phipps, R (1990) Prostaglandin E2 promotes IL-4-induced IgE and IgG1 synthesis. Journal of Immunology 145, 2644–2651.CrossRefGoogle ScholarPubMed
Sanderson, P, MacPherson, G, Jenkins, CH & Calder, PC (1997) Dietary fish oil diminishes the antigen presentation activity of rat dendritic cells. Journal of Leukocyte Biology 62, 771–777.CrossRefGoogle ScholarPubMed
Sarzotti, M, Robbins, DS & Hoffman, PM (1996) Induction of protective CTL responses in newborn mice by a murine retrovirus. Science 271, 1726–1728.CrossRefGoogle ScholarPubMed
Scott, WA, Zrike, JM, Hamill, AL, Kempe, J & Cohn, ZA (1980) Regulation of arachidonic acid metabolites in macrophages. Journal of Experimental Medicine 152, 324–335.CrossRefGoogle ScholarPubMed
Selivonchick, DP & Johnston, PV (1975) Fat deficiency in rats during development of the central nervous system and susceptibility to experimental allergic encephalomyelitis. Journal of Nutrition 105, 288–300.CrossRefGoogle ScholarPubMed
Shi, HN, Grusby, MJ & Nagler-Anderson, CN (1999) Orally induced peripheral nonresponsiveness is maintained in the absence of functional Th1 or Th2 cells. Journal of Immunology 162, 5143–5148.CrossRefGoogle ScholarPubMed
Shipman, PM, Schmidt, RR & Chepenik, KP (1988) Relation between arachidonic acid metabolism and development of thymocytes in fetal thymic organ cultures. Journal of Immunology 140, 2714–2720.CrossRefGoogle ScholarPubMed
Sinclair, HM (1990) Essential fatty acids – an historical perspective. Transactions of the Biochemical Society 18, 756–761.CrossRefGoogle ScholarPubMed
Strobel, S (2001) Immunity induced after a feed of antigen during early life: oral tolerance versus sensitisation. Proceedings of the Nutrition Society 60, 437–442.CrossRefGoogle Scholar
Strobel, S & Mowat, AM (1998) Immune responses to dietary antigens: oral tolerance. Immunology Today 19, 173–181.CrossRefGoogle ScholarPubMed
Tripp, CS, Wyche, A, Unanue, ER & Needleman, P (1986) The functional significance of the regulation of macrophage Ia expression by endogenous arachidonate metabolites in vitro. Journal of Immunology 137, 3915–3920.CrossRefGoogle ScholarPubMed
Ushikubi, F, Aiba, Y, Nakamura, K, Namba, T, Hirata, M, Mazda, O, Katsura, Y & Narumiya, S (1993) Thromboxane A2 receptor is highly expressed in mouse immature thymocytes and mediates DNA fragmentation and apoptosis. Journal of Experimental Medicine 178, 1825–1830.CrossRefGoogle ScholarPubMed
Vidard, L, Colarusso, LJ & Benacerraf, B (1995) Specfic T-cell tolerance may refelct selective activation of lymphokine synthesis. Proceedings of the National Academy of Sciences USA 92, 2259–2262.CrossRefGoogle Scholar
Wardrop, RM & Whitacre, CC (1999) Oral tolerance in the treatment of inflammatory autoimmune diseases. Inflammation Research 48, 106–119.CrossRefGoogle ScholarPubMed
Weiner, HL (1997) Oral tolerance: immune mechanisms and the treatment of autoimmune diseases. Immunology Today 18, 335–343.CrossRefGoogle ScholarPubMed
Williamson, E, O'Malley, JM & Viney, JL (1999) Visualizing the T-cell response elicited by oral administration of soluble protein antigen. Immunology 97 565–572.CrossRefGoogle ScholarPubMed