Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-26T08:57:07.725Z Has data issue: false hasContentIssue false

Dietary modification of inflammation with lipids

Published online by Cambridge University Press:  05 March 2007

Philip C. Calder*
Affiliation:
Institute of Human Nutrition, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
*
Corresponding author: Professor P. C. Calder, fax +44 23 8059 4383, email pcc@soton.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.

The n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoicacid (DHA) are found in high proportions in oily fish and fish oils. The n-3 PUFA are structurally and functionally distinct from the n-6 PUFA. Typically, human inflammatory cells contain high proportions of the n-6 PUFA arachidonic acid and low proportions of n-3 PUFA. The significance of this difference is that arachidonic acid is the precursor of 2-series prostaglandins and 4-series leukotrienes, which are highly-active mediators of inflammation. Feeding fish oil results in partial replacement of arachidonic acid in inflammatory cell membranes by EPA. This change leads to decreased production of arachidonic acid-derived mediators. This response alone is a potentially beneficial anti-inflammatory effect of n-3 PUFA. However, n-3 PUFA have a number of other effects which might occur downstream of altered eicosanoid production or might be independent of this activity. For example, animal and human studies have shown that dietary fish oil results in suppressed production of pro-inflammatory cytokines and can decrease adhesion molecule expression. These effects occur at the level of altered gene expression. This action might come about through antagonism of the effects of arachidonic acid-derived mediators or through more direct actions on the intracellular signalling pathways which lead to activation of transcription factors such as nuclear factor kappa B (NFêB). Recent studies have shown that n-3 PUFA can down regulate the activity of the nuclear transcription factor NFêB. Fish oil feeding has been shown to ameliorate the symptoms in some animal models of chronic inflammatory disease and to protect against the effects of endotoxin and similar inflammatory challenges. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some patients with asthma, supporting the idea that the n-3 PUFA in fish oil are antiinflammatory. There are indications that inclusion of n-3 PUFA in enteral and parenteral formulas might be beneficial to patients in intensive care or post-surgery.

Type
Mechanisms in nutrient regulation of inflammation
Copyright
Copyright © The Nutrition Society 2002

References

Alexander, HR, Doherty, GM, Buresh, CM, Venzon, DJ & Norton, JA (1991) A recombinant human receptor antagonist to interleukin 1 improves survival after lethal endotoxemia in mice. Journal of Experimental Medicine 173, 10291032.CrossRefGoogle ScholarPubMed
Arnalich, F, Garcia-Palomero, E, Lopez, J, Jimenez, M, Madero, R, Renart, J, Vazquez, JJ & Montiel, C (2000) Predictive value of nuclear factor kB activity and plasma cytokine levels in patients with sepsis. Infection and Immunity 68, 19421945.CrossRefGoogle Scholar
Baldie, G, Kaimakamis, D & Rotondo, D (1993) Fatty acid modulation of cytokine release from human monocytic cells. Biochimica et Biophysica Acta 1179, 125133.CrossRefGoogle ScholarPubMed
Barton, RG, Wells, CL, Carlson, A, Singh, R, Sullivan, JJ & Cerra, FB (1991) Dietary omega-3 fatty acids decrease mortality and Kupffer cell prostaglandin E2 production in a rat model of chronic sepsis. Journal of Trauma 31, 768774.CrossRefGoogle Scholar
Beale, RJ, Bryg, DJ & Bihari, DJ (1999) Immunonutrition in the critically ill: a systematic review of clinical outcome. Critical Care Medicine 27, 27992805.CrossRefGoogle 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, apoliporotein A-II and acyl CoA oxidase gene expression by fibrates and dietary fatty acids. European Journal of Biochemistry 232, 179187.CrossRefGoogle Scholar
Betz, M & Fox, BS (1991) Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. Journal of Immunology 146, 108113.Google Scholar
Beutler, B, Milsark, IW & Cerami, AC (1985) Passive immunization against cachetin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229, 869871.Google Scholar
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, 343349.Google Scholar
Black, PN & Sharp, S (1997) Dietary fat and asthma: is there a connection? European Respiratory Journal 10, 612.CrossRefGoogle ScholarPubMed
Braga, M, Gianotti, L, Radaelli, G, Vignali, A, Mari, G, Gentilini, O &Di Carlo, V (1999) Perioperative immunonutrition in patientsundergoing cancer surgery. Archives of Surgery 134, 428433.CrossRefGoogle Scholar
Braga, M, Vignali, A, Gianotti, L, Cestari, A, Profili, M & Di Carlo, V (1996) Immune and nutritional effects of early enternal nutrition after major abdominal operations. European Journal of Surgery 162, 105112.Google Scholar
Breil, I, Koch, T, Heller, A, Schlotzer, E, Grunert, A, Van Ackern, K & Neuhof, H (1996) Alteration of n-3 fatty acid composition in lung tissue after short-term infusion of fish oil emulsion attenuates inflammatory vascular reaction. Critical Care Medicine 24, 18931902.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.CrossRefGoogle ScholarPubMed
Broughton, KS, Johnson, CS, Pace, BK, Liebman, M & Kleppinger, KM (1997) Reduced asthma symptoms with n-3 fatty acid ingestion are related to 5-series leukotriene production. American Journal of Clinical Nutrition 65, 10111017.CrossRefGoogle ScholarPubMed
Calder, PC (1997) N-3 polyunsaturated fatty acids and cytokine production in health and disease. Annals of Nutrition and Metabolism 41, 203234.Google Scholar
Calder, PC (1998) N-3 fatty acids and mononuclear phagocyte function. In Medicinal Fatty Acids in Inflammation, pp. 127 [Kremer, JM, editor]. Basel: Birkhauser Verlag.Google Scholar
Calder, PC (2001) n-3 Polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled waters or another fishy tale? Nutrition Research 21, 309341.Google Scholar
Calder, PC (2001) N-3 Fatty acids and rheumatoid arthritis. In Food and Nutritional Supplements in Health and Disease, pp. 175197 [Ransley, JK, Donnelly, JK and Read, NW, editors]. London: Springer Verlag.Google Scholar
Calder, PC, Bond, JA, Harvey, DJ, Gordon, S & Newsholme, EA (1990) Uptake of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis. Biochemical Journal 269, 807814.CrossRefGoogle ScholarPubMed
Calder, PC & Miles, EA (2000) Fatty acids and atopic disease. Pediatric Allergy and Immunology 11 Suppl., 2936.Google Scholar
Calder, PC & Zurier, RB (2001) Polyunsaturated fatty acids and rheumatoid arthritis. Current Opinion in Clinical Nutrition and Metabolic Care 4, 115121.CrossRefGoogle ScholarPubMed
Cannon, JG, Tompkins, RG, Gelfrand, JA, Michie, HR, Stanford, GG, Van Der, Meer JW, Endres, S, Lonnemann, G, Corsetti, J, Chernow, B, Wilmore, DW, Wolff, SM, Burke, JF & Dinarello, CA (1990) Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. Journal of Infectious Disease 161, 7984.CrossRefGoogle ScholarPubMed
Caughey, GE, Mantzioris, E, Gibson, RA, Cleland, LG & James, MJ (1996) The effect on human tumor necrosis factor a and interleukin 1 b production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. American Journal of Clinical Nutrition 63, 116122.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
Chen, F, Castranova, V, Shi, X & Demers, LM (1999) New insightsinto the role of nuclear factor- kB, a ubiquitous transcription factor in the initiation of diseases. Clinical Chemistry 45, 717.CrossRefGoogle Scholar
Chen, LH & Zhao, Y (2001) Eicosapentaenoic acid decreases lipopolysaccharide-stimulated tumor necrosis factor-alpha expression by inhibiting nuclear factor kappa B activation. FASEB Journal 15, A258.Google Scholar
Chinetti, G, Fruchart, JC & Staels, B (2000) Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflammation Research 49, 497505.CrossRefGoogle ScholarPubMed
Chinetti, G, Griglio, S, Antonucci, M, Torra, IP, Delerive, P, Majd, Z, Fruchart, JC, Chapman, J, Najib, J & Staels, B (1998) Activation of peroxisome-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages. Journal of Biological Chemistry 273, 2557325580.CrossRefGoogle Scholar
Chow, SC, Ansotegui, IJ & Jondal, M (1990) Inhibition of receptor-mediated calcium influx in T cells by unsaturated non-esterified fatty acids. Biochemical Journal 267, 727732.CrossRefGoogle Scholar
Christman, JW, Lancaster, LH & Blackwell, TS (1998) Nuclear factor- kB: a pivotal role in systemic inflammatory response syndrome and new target for therapy. Intensive Care Medicine 24, 11311138.Google Scholar
Chu, AJ, Walton, MA, Prasad, JK & Seto, A (1999) Blockade by polyunsaturated n-3 fatty acids of endotoxin-induced monocytic tissue factor activation is mediated by the depressed receptor expression in THP-1 cells. Journal of Surgical Research 87, 217224.CrossRefGoogle ScholarPubMed
Cleland, LG & James, MJ (2000) Fish oil and rheumatoid arthritis: antiinflammatory and collateral health benefits. Journal of Rheumatology 27, 23052307.Google ScholarPubMed
Curtis, CL, Hughes, CE, Flannery, CR, Little, CB, Harwood, JL & Caterson, B (2000) n-3 Fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. Journal of Biological Chemistry 275, 721724.Google Scholar
De Caterina, R, Cybulsky, MI, Clinton, SK, Gimbrone, MA & Libby, P (1994) The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arteriosclerosis and Thrombosis 14, 18291836.Google Scholar
De Caterina, R & Libby, P (1996) Control of endothelial leukocyte adhesion molecules by fatty acids. Lipids 31, S57S63.CrossRefGoogle ScholarPubMed
Delerive, P, Fruchart, JC & Staels, B (2001) Peroxisome proliferator-activated receptors in inflammation control. Journal of Endocrinology 169, 453459.Google Scholar
Devchand, PR, Keller, H, Peters, JM, Vazquez, M, Gonzalez, FJ & Wahli, W (1996) The PPARa-leukotriene B4 pathway to inflammation control. Nature 384, 3943.Google Scholar
Donnellan, CE, Tadayyon, M, Briscoe, C, Arch, J & Calder, PC (2000) The effect of dietary fatty acids on the expression of genes involved in lipid handling. Proceedings of the Nutrition Society 59, 111A.Google Scholar
Dunder, T, Kuikka, L, Turtinen, J, Rasanen, L & Uhari, M (2001) Diet, serum fatty acids, and atopic diseases in childhood. Allergy 56, 425428.CrossRefGoogle ScholarPubMed
Endres, S, Ghorbani, R, Kelley, VE, Georgilis, K, Lonnemann, G, Van Der Meer, JMW, Cannon, JG, Rogers, TS, Klempner, MS, Weber, PC, Schaeffer, EJ, Wolff, SM & Dinarello, CA (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.CrossRefGoogle ScholarPubMed
Ertel, W, Morrison, MH, Meldrum, DR, Ayala, A & Chaudry, IH (1992) Ibuprofen restores cellular immunity and decreases susceptibility to sepsis following hemorrhage. Journal of Surgical Research 53, 5561.Google Scholar
Faull, RJ (1995) Adhesion molecules in health and disease. Australian and New Zealand Journal of Medicine 25, 720730.CrossRefGoogle ScholarPubMed
Feldmann, M, Brennan, FM & Maini, RN (1996) Role of cytokinesin rheumatoid arthritis. Annual Review of Immunology 14, 397440.Google Scholar
Feldmann, M & Maini, RN (1999) The role of cytokines in the pathogenesis of rheumatoid arthritis. Rheumatology 38, Suppl. 2, 37.Google ScholarPubMed
Gadek, JE, Demichele, SJ, Karlstad, MD, Pacht, ER, Donahoe, M, Albertson, TE, Van Hoozen, C, Wennberg, AK, Nelson, J, Noursalehi, M & the Enteral Nutrition in ARDS Study Group (1999) Effect of enteral feeding with eicosapentaenoic acid, γ-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Critical Care Medicine 27, 14091420.CrossRefGoogle ScholarPubMed
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.Google Scholar
Geusens, PP (1998) n-3 Fatty acids in the treatment of rheumatoid arthritis. In Medicinal Fatty Acids in Inflammation, pp. 111123 [Kremer, JM, editor]. Basel: Birkhauser Verlag.CrossRefGoogle Scholar
Gianotti, L, Braga, M, Fortis, C, Soldini, L, Vignali, A, Colombo, S, Radaelli, G & Di Carlo, V (1999) A prospective, randomised clinical trial on perioperative feeding with an arginine-, omega-3 fatty acid-, and RNA-enriched enteral diet: effect on host response and nutritional status. Journal of Parenteral and Enteral Nutrition 23, 314320.Google Scholar
Gibney, MJ & Hunter, B (1993) The effects of short- and long-term supplementation with fish oil on the incorporation of n-3 polyunsaturated fatty acids into cells of the immune system in healthy volunteers. European Journal of Clinical Nutrition 47, 255259.Google Scholar
Gold, KN, Weyand, CM & Goronzy, JJ (1994) Modulation of helper T cell function by prostaglandins. Arthritis and Rheumatism 37, 925933.CrossRefGoogle ScholarPubMed
Grbic, JT, Mannick, JA, Gough, DB & Rodrick, ML (1991) The role of prostaglandin E2 in immune suppression following injury. Annals of Surgery 214, 253263.Google Scholar
Grimm, H, Tibell, A, Norrlind, B, Blecher, C, Wilker, S & Schwemmle, K (1994) Immunoregulation by parenteral lipids: impact of the n-3 to n-6 fatty acid ratio. Journal of Parenteral and Enteral Nutrition 18, 417421.CrossRefGoogle ScholarPubMed
Grimminger, F, Wahn, H, Kramer, HJ, Stevens, J, Mayer, K, Walmrath, D & Seeger, W (1995) Differential influence of arachidonic acid vs. eicosapentaenoic acid on experimental pulmonary-hypertension. American Journal of Physiology 268, H2252H2259.Google Scholar
Grimminger, F, Wahn, H, Mayer, K, Kiss, L, Walmrath, D & Seeger, W (1997) Impact of arachidonic acid versus eicosapentaenoic acid on exotoxin-induced lung vascular leakage – relation to 4-series versus 5-series leukotriene generation. American Journal of Respiratory and Critical Care Medicine 155, 513519.Google Scholar
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, 363367.CrossRefGoogle ScholarPubMed
Hellerstein, MK, Meydani, SN, Meydani, M, Wu, K & Dinarello, CA (1989) Interleukin-1-induced anorexia in the rat: influence of prostaglandins. Journal of Clinical Investigation 84, 228235.Google Scholar
Henderson, WR (1994) Role of leukotrienes in asthma. Annals of Allergy 72, 272278.Google ScholarPubMed
Hodge, L, Peat, JK & Salome, C (1994) Increased consumption of polyunsaturated oils may be a cause of increased prevalence of childhood asthma. Australian and New Zealand Journal of Medicine 24, 727.Google Scholar
Hughes, DA, Pinder, AC, Piper, Z, Johnson, IT & Lund, EK (1996) 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, 267272.CrossRefGoogle ScholarPubMed
Hughes, DA, Southon, S & Pinder, AC (1996) (n-3) Polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes in vitro. Journal of Nutrition 126, 603610.CrossRefGoogle ScholarPubMed
Hwang, D & Rhee, SH (1999) Receptor-mediated signaling pathways: potential targets of modulation by dietary fatty acids. American Journal of Clinical Nutrition 70, 545556.CrossRefGoogle ScholarPubMed
Jackson, SM, Parhami, F, Xi, X-P, Berliner, JA, Hsueh, WA, Law, RE & Demer, LL (1999) Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte–endothelial cell interaction. Arteriosclerosis Thrombosis and Vascular Biology 19, 20942104.Google Scholar
James, MJ & Cleland, LG (1997) Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Seminars in Arthritis and Rheumatism 27, 8597.Google Scholar
Jiang, CY, Ting, AT & Seed, B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 8286.Google Scholar
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, 3743.Google Scholar
Kamochi, M, Kamochi, F, Kim, YB, Sawh, S, Sanders, JM, Sarembock, I, Green, S, Young, JS, Ley, K, Fu, SM & Rose, CE (1999) P-selectin and ICAM-1 mediate endotoxin-induced neutrophil recruitment and injury to the lung and liver. American Journal of Physiology 277, L310L319.Google Scholar
Karin, M & Ben-Neriah, Y (2000) Phosphorylation meets ubiquination: the control of NF-kappaB activity. Annual Review of Immunology 18, 621663.Google Scholar
Karin, M & Delhase, M (2000) The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling. Seminars in Immunology 12, 8598.Google Scholar
Khair-El-Din, T, Sicher, SC, Vazquez, MA, Chung, GW, Stallwort, KA, Kitamura, K, Miller, RT & Lu, CY (1996) Transcription of the murine iNOS gene is inhibited by docosahexaenoic acid, a major constituent of fetal and neonatal sera as well as fish oils. Journal of Experimental Medicine 183, 12411246.Google Scholar
Khalfoun, B, Thibault, G, Bardos, P & Lebranchu, Y (1996) Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human lymphocyte-endothelial cell adhesion. Transplantation 62, 16491657.CrossRefGoogle ScholarPubMed
Khalfoun, B, Thibault, F, Watier, H, Bardos, P & Lebranchu, Y (1997) Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human endothelial cell production of interleukin-6. Advances in Experimental Biology and Medicine 400, 589597.Google Scholar
Kim, DN, Schmee, J & Thomas, WA (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.CrossRefGoogle Scholar
Kinsella, JE, 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 ScholarPubMed
Kliewer, SA, Lenhard, JM, Willson, TM, Patel, I, Morris, DC & Lehman, JM (1995) A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor g and promotes adipocyte differentiation. Cell 83, 813819.Google Scholar
Knapp, HR (1995) Omega-3 fatty-acids in respiratory diseases – A review. Journal of the American College of Nutrition 14, 1823.Google Scholar
Kremer, JM, Lawrence, DA, Jubiz, W, Di, Giacomo R, Rynes, K, Bartholomew, LE & Sherman, M (1990) Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Arthritis and Rheumatism 33, 810820.CrossRefGoogle ScholarPubMed
Kumasaka, T, Quinlan, WM, Doyle, NA, Condon, NA, Sligh, J, Takei, F, Beaudet, AL, Bennett, CF & Doerschuk, CM (1996) Role of intercellular adhesion molecule-1 (ICAM-1) in endotoxin-induced pneumonia evaluated using ICAM-1 antisense oligonucleotides, anti-ICAM-1 monoclonal antibodies, and ICAM-1 mutant mice. Journal of Clinical Investigation 97, 23622369.CrossRefGoogle ScholarPubMed
Lanza-Jacoby, S, Flynn, JT & Miller, S (2001) Parenteral supplementation with a fish oil emulsion prolongs survival and improves lymphocyte function during sepsis. Nutrition 17, 112116.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, 12171224.CrossRefGoogle ScholarPubMed
Leslie, CA, Gonnerman, WA, Ullman, MD, Hayes, KC, Franzblau, C & Cathcart, ES (1985) Dietary fish oil modulates macrophage fatty acids and decreases arthritis susceptibility in mice. Journal of Experimental Medicine 162, 13361349.CrossRefGoogle ScholarPubMed
Lewis, RA, Austen, KF & Soberman, RJ (1990) Leukotrienes and other products of the 5-lipoxygenase pathway: Biochemistry and relation to pathobiology in human diseases. New England Journal of Medicine 323, 645655.Google Scholar
Lo, CJ, Chiu, KC, Fu, MJ, Chu, A & Helton, S (2000) Fish oil modulates macrophage P44/42 mitogen-activated protein kinase activity induced by lipopolysaccharide. Journal of Parenteral and Enteral Nutrition 24, 159163.Google Scholar
Mccabe, AJ, Wallace, J, Gilmore, W, Strain, JJ & Mcglynn, H (1999) The effect of eicosapentaenoic acid on matrix metalloproteinase gene expression. Lipids 34, S217S218.Google Scholar
Mccann, ME, Moore, JN, Carrick, JB & Barton, MH (2000) Effect of intravenous infusion of omega-3 and omega-6 lipid emulsions on equine monocyte fatty acid composition and inflammatory mediator production in vitro. Shock 14, 222228.CrossRefGoogle ScholarPubMed
Marx, N, Sukhova, GK, Collins, T, Libby, P & Plutzky, J (1999) PPARa activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation 99, 31253131.CrossRefGoogle Scholar
Mascioli, EA, Iwasa, Y, Trimbo, S, Leader, L, Bistrian, BR & Blackburn, GL (1989) Endotoxin challenge after menhaden oil diet: effects on survival of guinea pigs. American Journal of Clinical Nutrition 49, 277282.CrossRefGoogle ScholarPubMed
Mascioli, EA, 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.CrossRefGoogle ScholarPubMed
Mathison, JC, Wolfson, E & Ulevitch, RJ (1988) Participation of tumor necrosis factor in the mediation of Gram negative bacterial lipopolysaccharide-induced injury in rabbits. Journal of Clinical Investigation 81, 19251937.CrossRefGoogle ScholarPubMed
May, CL, Southwoth, AJ & Calder, PC (1993) Inhibition of lymphocyte protein kinase C by unsaturated fatty acids. Biochemical and Biophysical Research Communications 195, 823828.Google Scholar
Meydani, SN, Endres, S, Woods, MM, Goldin, BR, Soo, C, Morrill-Labrode, A, Dinarello, C & 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, 547555.Google Scholar
Meydani, SN, Lichtenstein, AH, Cornwall, S, Meydani, M, Goldin, BR, Rasmussen, H, Dinarello, CA & Schaefer, EJ (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
Miles, EA, Thies, F, Wallace, FA, Powell, JR, Hirst, TL, Newsholme, EA & Calder, PC (2001) Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations. Clinical Science 100, 91100.CrossRefGoogle ScholarPubMed
Miles, EA, Wallace, FA & Calder, PC (2000) Dietary fish oil reducesintercellular adhesion molecule 1 and scavenger receptor expression on murine macrophages. Atherosclerosis 152, 4350.Google Scholar
Mulrooney, HM & Grimble, RF (1993) Influence of butter and ofcorn, coconut and fish oils on the effects of recombinant human tumour necrosis factor-a in rats. Clinical Science 84, 105112.CrossRefGoogle Scholar
Obata, T, Nagakura, T, Masaki, T, Maekawa, K & Yamashita, K (1999) Eicosapentaenoic acid inhibits prostaglandin D2 generation by inhibiting cyclo-oxygenase-2 in cultured human mast cells. Clinical and Experimental Allergy 29, 11291135.CrossRefGoogle ScholarPubMed
Okusawa, S, Gelfrand, JA, Ikejima, T, Connolly, RJ & Dinarello, CA(1988) Interleukin 1 induces a shock-like state in rabbits.Synergism with tumor necrosis factor and effect of cyclooxygenase inhibition. Journal of Clinical Investigation 81, 11621172.Google Scholar
Panayi, GS (1999) Targetting of cells involved in the pathogenesis of rheumatoid arthritis. Rheumatology 38 Suppl. 2, 810.Google Scholar
Pfeffer, K, Matsuyama, T, Kundig, TM, Wakeham, A, Kishihara, K, Shahinlan, A, Wiegmann, K, Ohashi, PS, Kronke, M & Mak, TW (1993) Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73, 457467.CrossRefGoogle ScholarPubMed
Pomposelli, J, Mascioli, EA, Bistrian, BR & Flores, SM (1990) Attenuation of the febrile response in guinea pigs by fish oil enriched diets. Journal of Parenteral and Enteral Nutrition 13, 136140.Google Scholar
Poynter, ME & Daynes, RA (1998) Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor kappa B signalling, and reduces inflammatory cytokine production in aging. Journal of Biological Chemistry 273, 3283332841.CrossRefGoogle ScholarPubMed
Pscheidl, E, Schywalsky, M, Tschaikowsky, K & Boke-Prols, T (2000) Fish oil-supplemented parenteral diets normalize splanchnic blood flow and improve killing of translocated bacteria in a low-dose endotoxin rat model. Critical Care Medicine 28, 14891496.CrossRefGoogle Scholar
Raeburn, CD, Calkins, CM, Zimmerman, MA, Song, Y, Ao, LH, Banerjee, A, Meng, XZ & Harken, AH (2001) Vascular cell adhesion molecule-1 expression is obligatory for endotoxin-induced myocardial neutrophil accumulation and contractile dysfunction. Surgery 130, 319325.Google Scholar
Rayon, JI, Carver, JD, Wyble, LE, Wiener, D, Dickey, SS, Benford, VJ, Chen, LT & Lim, DV (1997) The fatty acid composition of maternal diet affects lung prostaglandin E2 levels and survival from group B Streptococcal sepsis in neonatal rat pups. Journal of Nutrition 127, 19891992.CrossRefGoogle Scholar
Renier, G, Skamene, E, De Sanctis, J & Radzioch, D (1993) Dietaryn-3 polyunsaturated fatty acids prevent the developmentof atherosclerotic lesions in mice: Modulation of macrophage secretory activities. Arteriosclerosis and Thombosis 13, 15151524.CrossRefGoogle Scholar
Ricote, M, Li, AC, Willson, TM, Kelly, CJ & Glass, CK (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391, 7982.Google Scholar
Robinson, DR, Urakaze, M, Huang, R, Taki, H, Sugiyama, E, Knoell, CT, Xu, L, Yeh, ETH & Auron, PE (1996) Dietary marine lipids suppress continuous expression on interleukin-1 b gene expression. Lipids 31, S23S31.CrossRefGoogle Scholar
Rola-Pleszczynski, M & Stankova, J (1992) Cytokine gene regulation by PGE2, LTB4 and PAF. Mediators of Inflammation 1, 58.Google Scholar
Ross, JA, Moses, AGW & Fearon, KCH (1999) The anti-catabolic effects of n-3 fatty acids. Current Opinion in Clinical Nutrition and Metabolic Care 2, 219226.Google Scholar
Sadeghi, S, Wallace, FA & Calder, PC (1999) Dietary lipids modify the cytokine response to bacterial lipopolysaccharide in mice. Immunology 96, 404410.CrossRefGoogle ScholarPubMed
Sanderson, P & Calder, PC (1998) Dietary fish oil diminishes lymphocyte adhesion to macrophage and endothelial cell monolayers. Immunology 94, 7987.CrossRefGoogle ScholarPubMed
Sanderson, P & Calder, PC (1998) Dietary fish oil appears to inhibit the activation of phospholipase C- g in lymphocytes. Biochimica et Biophysica Acta 1392, 300308.CrossRefGoogle Scholar
Sanderson, P, Yaqoob, P & Calder, PC (1995) Effects of dietary lipid manipulation upon rat spleen lymphocyte functions and theexpression of lymphocyte surface molecules. Journal of Nutritional and Environmental Medicine 5, 119132.Google Scholar
Sanderson, P, Yaqoob, P & Calder, PC (1995) Effects of dietary lipid manipulation upon graft vs. host and host vs. graft responses in the rat. Cellular Immunology 164, 240247.Google Scholar
Sano, H, Hla, T, Maier, JAM, Crofford, LJ, Case, JP, Maciag, T & Wilder, RL (1992) In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis. Journal of Clinical Investigation 89, 97108.Google Scholar
Sasaki, T, Kanke, Y, Kudoh, K, Nagahashi, M, Toyokawa, M, Matsuda, M, Shimizu, J & Takita, T (2000) Dietary n-3 polyunsaturated fatty acid and status of immunocompetent cells involved in innate immunity in female rats. Annals of Nutrition and Metabolism 44, 3842.Google Scholar
Schoonjans, K, Staels, B & Auwerx, J (1996) The peroxisome proliferator activated receptors (PPARs) and their effects on lipidmetabolism and adipocyte differentiation. Biochimica et Biophysica Acta 1302, 93109.CrossRefGoogle Scholar
Schulzki, C, Mertes, N, Wenn, A, Goeters, C, Grimm, H, Schlotzer, E, Spindler, A, Gokorsch, S, Mayer, K, Grimminger, F, Seeger, W, Kuhn, KS & Furst, P (1999) Effects of a new type of lipid emulsion based on soybean oil, MCT, olive oil and fish oil (SMOF) in surgical patients. Clinical Nutrition 18 Suppl. 1, 7.Google Scholar
Sinha, B, Stoll, D, Weber, PC & Endres, S (1991) Polyunsaturated fatty acids modulate the synthesis of TNF-a and interleukin-1 b by human mononuclear cells in vitro. Cytokine 3, 475.CrossRefGoogle Scholar
Snijdewint, FGM, Kalinski, P, Wieringa, EA, Bos, JD & Kapsenberg, ML (1993) Prostaglandin E2 differentially modulates cytokine secretion profiles in human T-helper lymphocytes. Journal of Immunology 150, 53215329.Google Scholar
Sperling, RI (1995) Eicosanoids in rheumatoid arthritis. Rheumatological Disease Clinics of North America 21, 741758.Google Scholar
Sperling, RI, Benincaso, AI, Knoell, CT, Larkin, JK, Austen, KF & Robinson, DR (1993) Dietary w-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. Journal of Clinical Investigation 91, 651660.Google Scholar
Takano, H, Nagai, T, Asakawa, M, Toyozaki, T, Oka, T, Komuro, I, Saito, T & Masuda, Y (2000) Peroxisome proliferator-receptor activators inhibit lipopolysaccharide-induced tumor necrosis factor-alpha expression in neonatal rat cardiac myocytes. Circulation Research 87, 596602.Google Scholar
Tang, WW, Yi, ES, Remick, DG, Wittwer, A, Yin, SM, Qi, MY & Ulich, TR (1995) Intratracheal injection of endotoxin and cytokines. 9. Contribution of CD11a/ICAM-1 to neutrophil emigration. American Journal of Physiology 269, L653L659.Google Scholar
Tappia, PS, Man, WJ & Grimble, RF (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.Google Scholar
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, 551553.Google Scholar
Tepaske, R, Te Velthuis, H, Oudemans-Van Straaten, M, Heisterkamp, SH, Van Deventer, SJH, Ince, C, Eysman, L & Keseciogu, J (2001) Effect of preoperative oral immune-enhancing nutritional supplement on patients at risk of infection after cardiac surgery: a randomised placebo-controlled trial. Lancet 358, 696701.Google Scholar
Thies, F, Nebe-Von-Caron, G, Powell, JR, Yaqoob, P, Newsholme, EA & Calder, PC (2001) Dietary supplementation with g-linolenic acid or with fish oil decreases T lymphocyte proliferation in healthy older humans. Journal of Nutrition 131, 19181927.Google Scholar
Thomas, LT (1972) Notes of a biology-watcher. New England Journal of Medicine 287, 553555.Google Scholar
Tilley, SL, Coffman, TM & Koller, BH (2001) Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. Journal of Clinical Investigation 108, 1523.Google Scholar
Tracey, KJ, Beutler, B, Lowry, SF, Merryweather, J, Wolpe, S, Milsark, IW, Hariri, RJ, Fahey, TJ, Zentella, A, Albert, JD, Shires, GT & Cerami, A (1986) Shock and tissue injury induced by recombinant human cachectin. Science 234, 470474.Google Scholar
Tracey, KJ, Fong, Y, Hesse, DG, Manogue, KR, Lee, AT, Kuo, GC, Lowry, SF & Cerami, AC (1987) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330, 662664.Google Scholar
Vervloet, MG, Thijs, LG & Hack, CE (1998) Derangements of coagulation and fibrinoloysis in critically ill patients with sepsis andseptic shock. Seminars in Thrombosis and Hemostasis 24, 3344.CrossRefGoogle Scholar
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, 559565.Google Scholar
Volker, D & Garg, M (1996) Dietary n-3 fatty acid supplementation in rheumatoid arthritis – mechanisms, clinical outcomes, controversies, and future directions. Journal of Clinical and Biochemical Nutrition 20, 8397.Google Scholar
Wachtler, P, Konig, W, Senkal, M, Kemen, M & Koller, M (1997) Influence of a total parenteral nutrition enriched with w-3 fatty acids on leukotriene synthesis of peripheral leukocytes and systemic cytokine levels in patients with major surgery. Journal of Trauma 42, 191198.CrossRefGoogle Scholar
Wallace, FA, Miles, EA & Calder, PC (2000) Activation state alters the effect of dietary lipids on pro-inflammatory mediator production by murine macrophages. Cytokine 12, 13741379.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, 449457.Google Scholar
Wang, P, Anderson, PO, Chen, SW, Paulsson, KM, Sjogren, HO & Li, SL (2001) Inhibition of the transcription factors AP-1 and NF-kappa B in CD4 T cells by peroxisome proliferator-activated receptor gamma ligands. International Immunopharmacology 1, 803812.CrossRefGoogle ScholarPubMed
Wu, GH, Zhang, YW & Wu, ZH (2001) Modulation of postoperative immune and inflammatory response by immune-enhancing enteral diet in gastrointestinal cancer patients. World Review of Gastroenterology 7, 357362.Google Scholar
Xi, S, Cohen, D, Barve, S & Chen, LH (2001) Fish oil suppressed cytokines and nuclear factor kappaB induced by murine AIDS virus infection. Nutrition Research 21, 865878.Google Scholar
Xi, S, Cohen, D & Chen, LH (1998) Effects of fish oil on cytokines and immune functions of mice with murine AIDS. Journal of Lipid Research 39, 16771687.CrossRefGoogle ScholarPubMed
Xu, X, Otsuki, M, Saito, H, Sumitani, S, Yamamoto, H, Asanuma, N, Kouhara, H & Kasayama, S (2001) PPAR alpha and GR differentially down-regulate the expression of nuclear factor-kappa B-responsive genes in vascular endothelial cells. Endocrinology 142, 33323339.CrossRefGoogle Scholar
Yaqoob, P & Calder, PC (1995) Effects of dietary lipid manipulationupon inflammatory mediator production by murine macrophages. Cellular Immunology 163, 120128.CrossRefGoogle ScholarPubMed
Yaqoob, P, Pala, HS, Cortina-Borja, M, Newsholme, EA & Calder, PC(2000) Encapsulated fish oil enriched in a-tocopherol altersplasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. European Journal of Clinical Investigation 30, 260274.CrossRefGoogle Scholar