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n-3 Fatty acids and the inflammatory response — biological background

R. De Caterina*,1,2 and G. Basta2

1 Chair of Cardiology, G. d'Annunzio University, Chieti, Italy
2 CN.R. Institute of Clinical Physiology, Pisa, Italy

* Correspondence: Raffaele De Caterina, MD, PhD, Laboratory for Thrombosis and Vascular Research, C.N.R. Institute of Clinical Physiology, Via Moruzzi 8, 1-56100 Pisa, Italy.
rdecater{at}ifc.cnr.it

Abstract

Inflammation can be defined as the reaction of a living vascularized tissue to a localized damage, and plays a role in both normal repair reactions and in the pathogenesis of disease. Inflammatory phenomena are at the basis of a number of disease processes in virtually any systemic or organ-specific disease, ranging from classical rheumatic diseases to bronchial airway hyper-responsiveness, inflammatory bowel disease, kidney diseases, psoriasis and atopic eczema. Modulation of long-chain polyunsaturated fatty acid intake, mostly by increasing the relative proportions of n-3 versus n-6 fatty acids, is the clearest example of how diet may modulate the inflammatory process. It is possible that many of the environmentally attributable epidemiological differences in the incidence of inflammatory diseases among different populations can be tracked back to different nutritional intake of selected, quantitatively minor nutritional components such as omega-3 fatty acids. The increase in dietary intake of these compounds, or their pharmacological supplementation, leads to a moderate quenching of the inflammatory reaction which may prove useful in selected clinical conditions. The clarification of the mechanisms of the biological action of these, as well as of other dietary components, and a better documentation of the spectrum of clinical possibilities offered by dietary manipulation in the intake of such compounds, linking together classical nutritional science, molecular biology, epidemiology and clinical medicine, are a frontier for nutritional research in the years to come. This nutritional approach promises to gain a place in the therapy of some inflammatory disorders.

References

  1. Robbins S, Cotran R, Kumar V. Inflammation and repair processes. Pathologic Basis of Disease. 3rd edn. Philadelphia-London-Toronto: WB Saunders Co; 1984.
  2. Henderson W. The role of leukotrienes in inflammation. Ann Intern Med. 1994;121:684–697[Abstract/Free Full Text]
  3. Ben-Baruch A, Michiel D, Oppenheim J. Signals and receptors involved in recruitment of inflammatory cells. J Biol Chem. 1995;270:11703–11706[Free Full Text]
  4. Simopoulos A. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr. 1991;54:438–463[Abstract/Free Full Text]
  5. De Caterina R, Endres S, Kristensen S, Schmidt E. n-3 Fatty Acids and Vascular Disease. 3rd edn. Berlin: Springer; 1993. p. 167
  6. Kristensen S, Schmidt E, De Caterina R, Endres S. n-3 Fatty Acids: Prevention and Treatment in Vascular Disease. 3rd edn. Berlin: Springer; 1995. p. 230
  7. Kristensen S, De Caterina R, Schmidt E, Endres S. Fish oil and ischaemic heart disease. Br Heart J. 1993;70:212–214[Free Full Text]
  8. Knapp H, FitzGerald G. Anti-hypertensive effects of fish oil. A controlled study of polyunsaturated fatty acid supplementation in essential hypertension. N Engl J Med. 1989;320:1037–1043[Abstract]
  9. Appel I, Miller E, Seidler A, Whelton P. Does supplementation of diet with fish oil reduce blood pressure—a metaanalysis of controlled clinical trials. Arch Intern Med. 1993;153:1429–1438[Abstract/Free Full Text]
  10. Schmidt E, Kristensen S, De Caterina R, Endres S. The effects of n-3 fatty acids on plasma lipids and lipoproteins and other cardiovascular risk factors in patients with hyperlipidemia. Atherosclerosis. 1993;103:107–121[CrossRef][Web of Science][Medline]
  11. Galli C, Butrum R. Dietary {omega}3 fatty acids and cancer: an overview. Simopoulos A, Kifer R, Martin R, Barlow S. World Rev Nutr Diet. 2nd edn. 1991. p. 446–461
  12. Malasanos T, Stacpoole P. Biological effects of {omega}3 fatty acids in diabetes mellitus. Diabetes Care. 1991;14:116–179
  13. De Caterina R, Endres S, Kristensen S, Schmidt F. n-3 Fatty acids and renal diseases. Am J Kidney Dis. 1994;24:397–410[Web of Science][Medline]
  14. Kromann N, Green A. Epidemiological studies in the Upernavik District, Greenland. Acta Med Scand. 1980;208:401–406[Web of Science][Medline]
  15. Dyerberg J, Bang H, Hjorne N. Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr. 1975;28:958–966[Abstract/Free Full Text]
  16. Bang H, Dyerberg J, Hjorne N. The composition of food consumed by Greenland Eskimos. Acta Med Scand. 1976;200:69–73[Web of Science][Medline]
  17. Popp-Snijders C, Schouten J, van der Meer J, van der Veen E. Fatty-fish induced changes in membrane lipid composition and viscosity of human erythrocyte suspensions. Scand J Clin Invest. 1986;46:253–258[Web of Science][Medline]
  18. Singer P, Jaeger W, Voigt S, Thiel H. Defective desaturation and elongation of n-6 and n-3 fatty acids in hypertensive patients. Prostaglandins Leukot Med. 1984;15:159–165[CrossRef][Web of Science][Medline]
  19. Sharp J, White D, Chious X, et al. Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2. J Biol Chem. 1991;266:14850–14853[Abstract/Free Full Text]
  20. Clark J, Lin L, Kriz R, et al. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. Cell. 1991;65:1043–1051[CrossRef][Web of Science][Medline]
  21. Mayer R, Marshall L. New insights on mammalian phospholipase A2(s); comparison of arachidonyl-selective and non-selective enzymes. FASEB J. 1993;7:339–348[Abstract]
  22. Glaser Y, Mobilio D, Chang J, Senko N. Phospholipase A2 enzymes: regulation and inhibition. Trends Pharmacol Sci. 1993;14:92–98[CrossRef][Medline]
  23. Clark M, Ögü L, Conway T, Dispoto J, Crooke S, Bomalaski J. Cloning of a phospholipase A2-activating protein. Proc Natl Acad Sci USA. 2nd edn. 1991. p. 5418–5422
  24. Kramer R, Hession C, Johansen B, et al. Structure and properties of a human non-pancreatic phospholipase A2. J Biol Chem. 1989;264:5768–5775[Abstract/Free Full Text]
  25. Leaf A, Weber P. Cardiovascular effects of n-3 fatty acids. N Engl J Med. 1988;318:549–557[Web of Science][Medline]
  26. Knapp H. Omega-3 fatty acids in respiratory diseases: a review. J Am Coll Nutr. 1995;14:18–23[Abstract]
  27. Patrono C, Ciabattoni G, Remuzzi G, et al. Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus. J Clin Invest. 1985;76:1011–1018
  28. Ciabattoni G, Cinotti G, Pierucci A, et al. Effect of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin. N Engl J Med. 1984;310:279–283[Abstract]
  29. Craven P, Melhem M, DeRubertis F. Thromboxane in the pathogenesis of glomerular injury in diabetes. Kidney Int. 1992;42:937–946[Web of Science][Medline]
  30. Perico N, Benigni A, Zoja C, Delaini F, Remuzzi G. Functional significance of exaggerated renal thromboxane A2 synthesis induced by cyclosporin A. Am J Physiol. 1986;251:F581–F587
  31. Foegh M, Lim K, Alijani M, Helfrich G, Ramweli P. Thromboxane and inflammatory cell infiltration in the allograft of renal transplant patients. Transplant Proc. 2nd edn. 1987. p. 3633–3636
  32. Remuzzi G, Imberti L, Rossini M, et al. Increased glomerular thromboxane synthesis as a possible cause of proteinuria in experimental nephrosis. J Clin Invest. 1985;75:94–101
  33. Stahl R. Die Bedeutung von Eicosanoiden bei glomerulären Erkrankungen. Klin Wochenschr. 1986;64:813–823[CrossRef]
  34. Remuzzi G, FitzGerald G, Patrono C. Thromboxane synthesis and action within the kidney. Kidney Int. 1992;41:1483–1493[Web of Science][Medline]
  35. De Caterina R, Caprioli R, Giannessi D, et al. n-3 Polyunsaturated fatty acids reduce proteinuria in patients with chronic glomerular disease. Kidney Int. 1993;44:843–850[Web of Science][Medline]
  36. Dyerberg J, Bang H, Stofferson E, Moncada S, Vane J. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis. Lancet. 1978;ii:117–119
  37. von Schacky C, Fischer S, Weber P. Long-term effects of dietary marine {omega}-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoids formation in humans. J Clin Invest. 1985;76:1626–1631
  38. von Schacky C, Weber P. Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahexaenoic acids in humans. J Clin Invest. 1985;76:2446–2450
  39. De Caterina R, Giannessi D, Mazzone A, et al. Vascular prostacyclin is increased in patients ingesting omega-3 polyunsaturated fatty acids before coronary artery bypass graft surgery. Circulation. 1990;82:428–438[Abstract/Free Full Text]
  40. Endres S, Ghorbany R, Kelley V, et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med. 1989;320:265–271[Abstract]
  41. Meydani S, Endres S, Wood M, et al. Oral n-3 fatty acid supplementation suppresses cytokine production and lymphocyte proliferation. Comparison in young and older women. J Nutr. 1991;121:547–555
  42. De Caterina R, Cybulsky MI, Clinton SK, Gimbrone MA Jr, Libby P. The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of pro-atherogenic and pro inflammatory proteins in human endothelial cells. Arterioscler Thromb. 1994;14:1829–1836[Abstract/Free Full Text]
  43. De Caterina R, Cybulsky MI, Clinton SK, Gimbrone MA Jr, Libby P. The Omega-3 fatty acids and endothelial leukocyte adhesion molecules. Prostaglandins Leukot Essent Fatty Acids. 1995;52:192–195
  44. De Caterina R, Libby P. Control of endothelial leukocyte adhesion molecules by fatty acids. Lipids. 1996;31(Suppl 1):557–563[CrossRef][Web of Science][Medline]
  45. Weber C, Erl W, Pietsch A, Danesch U, Weber P. Docosahexaenoic acid selectively attenuates induction of vascular cell adhesion molecule-1 and subsequent monocytic cell adhesion to human endothelial cells stimulated by tumor necrosis factor-alpha. Arterioscler Thromb Vase Biol. 1995;15:622–628
  46. Bauerle P. The inducible transcription activator NF-KB: regulation by distinct protein subunits. Biochim Biophys Acta. 1991;1072:63–80[Medline]
  47. Collins T. Endothelial nuclear factor-{kappa}B and the initiation of the atherosclerotic lesion. Lab Invest. 1993;68:499–508[Web of Science][Medline]
  48. Collins T, Read MA, Neish AS, Whitley MZ, Thanos D, Maniatis T. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J. 1995;9:899–909[Abstract]
  49. Hansen J, Olsen J, Wilsgard I, Osterud B. Effects of dietary supplementation with cod liver oil on monocyte thromboplastin synthesis, coagulation and fibrinolysis. J Intern Med Suppl. 1989;225:133–139
  50. Tremoli E, Eligini S, Colli S, et al. Effects of omega 3 fatty acid ethyl esters on monocyte tissue factor expression. World Rev Nutr Diet. 1994;76:55–59[Medline]
  51. Fox P, DiCorleto P. Fish oils inhibit endothelial cell production of platelet-derived growth factor-like protein. Science. 1988;241:453–456[Abstract/Free Full Text]
  52. Kaminski W, Jendraschak E, Kiefl R, von Schacky C. Dietary omega-3 fatty acids lower levels of platelet-derived growth factor MRNA in human mononuclear cells. Blood. 1993;71:1871–1879
  53. Habib A, Lubrano L, Basta G, et al. n-3 polyunsaturated fatty acids inhibit COX-2 expression. Washington, DC, USA, August 14–21, 1999Thromb Haemost. 2nd edn. 1999. p. 348 (Suppl)
  54. Lee T, Hoover R, Williams J, et al. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med. 1985;312:1217–1224[Abstract]
  55. Schmidt E, Dyerherg J. n-3 Fatty acids and leukocytes. J Intern Med. 1989;225(Suppl 1):151–158
  56. Schmidt E, Pedersen J, Ekelund S, Grunnet N, Jersild C, Dyerberg J. Cod liver oil inhibits neutrophil and monocyte chemotaxis in healthy males. Atherosclerosis. 1989;77:53–57[CrossRef][Web of Science][Medline]
  57. Schmidt E, Pedersen J, Varming K, et al. n-3 Fatty acids and leukocyte chemotaxis. Effects in hyperlipidemia and doseresponse studies in healthy men. Arterioscler Thromb. 1991;11 [:429–435
  58. Fisher M, Upchurch K, Levine P, et al. Effects of dietary fish oil supplementation on polymorphonuclear leukocyte inflammatory potential. Inflammation. 1986;10:387–392[CrossRef][Web of Science][Medline]
  59. Terano T, Hirai A, Hamazaki T, et al. Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects. Atherosclerosis. 1983;46:321–331[CrossRef][Web of Science][Medline]
  60. Cartwright I, Pockley A, Galloway J, Greaves M, Preston F. The effects of dietary {omega}3 polyunsaturated fatty acids on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity in healthy volunteers. Atherosclerosis. 1985;55:267–281[CrossRef][Web of Science][Medline]
  61. Ernst F. Effects of n-3 fatty acids on blood theology. J Intern Med. 1989;225(Suppl 731):129–133[Web of Science][Medline]
  62. Popp-Snijders C, Schouten J, van Blitterswijk W, van der Veen E. Changes in the membrane lipid composition of human erythrocytes after dietary supplementation of (n-3) polyunsaturated fatty acids. Maintenance of membrane fluidity. Biochim Biophys Acta. 1986;854:31–36[Medline]
  63. Hostmark A, Bjerkedal T, Kierulf P, Flaten H, Ulshagen K. Fish oil and plasma fibrinogen. Br Med J. 1988;297:180–181
  64. Radak K, Deck C, Huster G. Dietary supplementation with low-dose fish oils lowers fibrinogen levels: a randomized, double-blind controlled study. Ann Intern Med. 1989;111:757–758
  65. Flaten H, Hostmark A, Kierulf P, et al. Fish-oil concentrate. Effects on variables related to cardiovascular disease. Am J Clin Nutr. 1990;52:300–306[Abstract/Free Full Text]
  66. Boulanger C, Schini V, Hendrickson H, Vanhoutte P. Chronic exposure of cultured endothelial cells to eicosapentaenoic acid potentiates the release of endothelium-dependent relaxing factor(s). Br J Pharmacol. 1990;99:176–180[Web of Science][Medline]
  67. Vanhoutte P, Shimokawa H, Boulanger C. Fish oil and the platelet-blood vessel wall interaction. World Rev Nutr Diet. 1991;66:233–244[Medline]
  68. Coddee J, Croft E, Barden A, Mathews E, Vandongen R, Beilin L. An inhibitory effect of dietary polyunsaturated fatty acids on renin secretion in the isolated perfused rat kidney. J Hypertens. 1984;2:265–270[Medline]
  69. Goodfriend T, Ball D. Fatty acids effects on angiotensin receptors. J Cardiovasc Pharmacol. 1986;8:1276–1283[Web of Science][Medline]
  70. Sellmayer A, Obermeier H, Weber C, Weber P. Modulation of cell activation by n-3 fatty acids. De Caterina R, Endres S, Kristensen S, Schmidt E. n-3 Fatty Acids and Vascular Disease. 2nd edn. Berlin: Springer-Verlag; 1993. p. 21–30
  71. Weber C, Aepfelbacher M, Lux I, Zimmer B, Weber P. Docosahexaenoic acid inhibits PAF and LTD4-stimulated [Ca++]i increase in differentiated monocytic U937 cells. Biochim Biophys Acta. 1991;1133:38–45[Medline]
  72. Locher R, Sachinidis A, Brunner C, Vetter W. Intracellular free calcium concentration and thromboxane A2 formation of vascular smooth muscle cells are influenced by fish oil and n-3 eicosapentaenoic acid. Scand J Lab Invest. 1991;51:541–547
  73. Hallaq H, Smith T, Leaf A. Protective effect of eicosapentaenoic acid on ouabain toxicity in neonatal rat cardiac myocytes. Proc Natl Acad Sci USA. 2nd edn. 1990. p. 7834–7838
  74. Hallaq H, Smith T, Leaf A. Modulation of dihydropyridinesensitive calcium channels in heart cells by fish oil fatty acids. Proc Natl Acad Sci USA. 2nd edn. 1992. p. 1760–1764
  75. Swann P, Parent C, Croset M, et al. Enrichment of platelet phospholipids with eicosapentaenoic acid and docosahexaenoic acid inhibits thromboxane A2/prostaglandin H2 receptor binding and function. J Biol Chem. 1990;265:21692–21697[Abstract/Free Full Text]
  76. Ehringer W, Belcher D, Wassal S, Stillweli W. A comparison of the effects of linolenic (18:3 {omega}3) and docosahexaenoic (22:6 {omega}3) acids on phospholipid bilayers. Chem Phys Lipids. 1990;54:79–88[CrossRef][Web of Science][Medline]
  77. Salem N, Kim H, Yergey J. Docosahexaenoic acid: membrane function and metabolism. Simopoulos A, Kifer R, Martin R. Health Effects of Polyunsaturated Fatty Acids in Seafoods. 2nd edn. Orlando, FL: Academic Press; 1986. p. 263–318
  78. Medini L, Colli S, Mosconi C, Tremoli E, Galli C. Diets rich in n-9, n-6 and n-3 fatty acids differentially affect the generation of inositol phosphates and of thromboxane by stimulated platelets in the rabbit. Biochim Pharmacol. 1990;39:129–133[CrossRef][Web of Science][Medline]
  79. Locher R, Sachinidis A, Steiner A, Vogt E, Vetter W. Fish oil affects phosphoinositide turnover and thromboxane A metabolism in cultured vascular smooth cells. Biochim Biophys Acta. 1989;1012:279–283[Medline]
  80. Force T, Hyman G, Hajjar R, Sellmayer A, Bonventre J. Non cycloxygenase metabolites of arachidonic acid amplify the vasopressin-induced Ca2+ signal in glomerular mesangial cells by releasing Ca 21 from intracellular stores. Biol Chem. 1991;266:4295–4302
  81. Oliw E, Sprecher H. Metabolism of polyunsaturated (n-3) fatty acids by monkey seminal vesicles: isolation and biosynthesis of {omega}3 epoxides. Biochim Biophys Acta. 1991;1086:287–294[Medline]
  82. Voss A, Reinhart M, Sankarappa S, Sprecher H. The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7, 10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturate. J Biol Chem. 1991;266:19995–20000[Abstract/Free Full Text]

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