Skip to main content

Advertisement

SpringerLink
Log in

Modulation of immune cell function by polyunsaturated fatty acids

  • Review Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

The n–3 and n–6 polyunsaturated fatty acids (PUFAs) are essential dietary constituents. They are important as a source of energy, as structural components of cell membranes, and as signalling molecules. They have been demonstrated to be potent modulators of the immune response, and research has endeavoured to optimise the ratio of n–3 to n–6 PUFAs in the lipid component of total parenteral nutrition (TPN) to optimise their beneficial effects in the clinical setting. Critically ill neonates on TPN have an increased incidence of sepsis, and additional studies have determined that lipid emulsions depress various elements of cellular immune responses in monocytes, lymphocytes, and neutrophils. It has been proposed that PUFAs may mediate their manifold effects through the modification of eicosanoid production and by directly or indirectly modifying intracellular signal transduction pathways, including the alteration of gene transcription, in various tissues. They are susceptible to lipid peroxidation, and there is evidence that the products of this process may result in cell death by apoptosis, a nonphlogistic homeostatic process of cell deletion. PUFAs have been shown to induce apoptosis in primary lymphocytes, colonic mucosal cells, and various cell lines. Additionally, our laboratory has shown them to be potent inducers of apoptosis in neonatal monocytes. This may represent a novel mechanism whereby PUFAs may modify the immune response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Holman RT, George O (1988) Burr and the discovery of essential fatty acids. J Nutr 118:535–540

    Google Scholar 

  2. Holman RT (1998) The slow discovery of the importance of omega 3 essential fatty acids in human health. J Nutr 128:427S–433S

    Google Scholar 

  3. Konig D, Berg A, Weinstock C, Keul J, Northoff H (1997) Essential fatty acids, immune function, and exercise. Exerc Immunol Rev 3:1–31

    Google Scholar 

  4. Calder PC (1997) N–3 polyunsaturated fatty acids and immune cell function. Adv Enzyme Regul 37:197–237

    Google Scholar 

  5. Abumrad N, Coburn C, Ibrahimi A (1999) Membrane proteins implicated in long-chain fatty acid uptake by mammalian cells: CD36, FATP and FABPm. Biochim Biophys Acta 1441:4–13

    Google Scholar 

  6. Paulsrud JR, Pensler L, Whitten CF, Stewart S, Holman R (1972) T Essential fatty acid deficiency in infants induced by fat-free intravenous feeding. Am J Clin Nutr 25:897–904

    Google Scholar 

  7. Garnacho Montero J, Shou J, Ortiz Leyba C, Jimenez Jimenez FJ, Daly JM (1996) Lipids and immune function. Nutr Hosp 11:230–237

    Google Scholar 

  8. Muhlebach SF, Steger PJ (1998) Lipid peroxidation of intravenous fat emulsions: a pharmaceutical issue with clinical impact? Nutrition 14:720–721

    Google Scholar 

  9. Carpentier A, Mittelman SD, Bergman RN, Giacca A, Lewis GF (2000) Prolonged elevation of plasma free fatty acids impairs pancreatic beta-cell function in obese nondiabetic humans but not in individuals with type 2 diabetes. Diabetes 49:399–408

    Google Scholar 

  10. Carpentier YA, Dupont IE (2000) Advances in intravenous lipid emulsions. World J Surg 24:1493–1497

    Google Scholar 

  11. Fischer GW, Hunter KW, Wilson SR, Mease AD (1980) Diminished bacterial defences with intralipid. Lancet 2:819–820

    Google Scholar 

  12. Spratt MG, Kratzing CC (1975) Oleic acid as a depressant of reticuloendothelial activity in rats and mice. J Reticuloendothel Soc 17:135–140

    Google Scholar 

  13. Group TVATPNCS (1991) Perioperative total parenteral nutrition in surgical patients. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. N Engl J Med 325:525–532

    Google Scholar 

  14. Freeman J, Goldmann DA, Smith NE, Sidebottom DG, Epstein MF, Platt R (1990) Association of intravenous lipid emulsion and coagulase-negative staphylococcal bacteremia in neonatal intensive care units. N Engl J Med 323:301–308

    Google Scholar 

  15. Andrew G, Chan G, Schiff D (1976) Lipid metabolism in the neonate. I. The effects of Intralipid infusion on plasma triglyceride and free fatty acid concentrations in the neonate. J Pediatr 88:273–278

    Google Scholar 

  16. Hardy G, Allwood MC (1997) Oxidation of intravenous lipid emulsions. Nutrition 13:230

    Google Scholar 

  17. Helbock HJ, Motchnik PA, Ames BN (1993) Toxic hydroperoxides in intravenous lipid emulsions used in preterm infants. Pediatrics 91:83–87

    Google Scholar 

  18. Pitkanen OM (1992) Peroxidation of lipid emulsions: a hazard for the premature infant receiving parenteral nutrition? Free Radic Biol Med 13:239–245

    Google Scholar 

  19. Basu R, Muller DP, Papp E, Merryweather I, Eaton S, Klein N, Pierro A (1999) Free radical formation in infants: the effect of critical illness, parenteral nutrition, and enteral feeding. J Pediatr Surg 34:1091–1095

    Google Scholar 

  20. Wu GH, Jarstrand C, Nordenstrom J (1999) Phagocyte-induced lipid peroxidation of different intravenous fat emulsions and counteractive effect of vitamin E. Nutrition 15:359–364

    Google Scholar 

  21. Goode HF, Cowley HC, Walker BE, Howdle PD, Webster NR (1995) Decreased antioxidant status and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction. Crit Care Med 23:646–651

    Google Scholar 

  22. Furukawa K, Tashiro T, Yamamori H, Takagi K, Morishima Y, Sugiura T, Otsubo Y, Hayashi N, Itabashi T, Sano W, Toyoda Y, Nitta H, Nakajima N (1999) Effects of soybean oil emulsion and eicosapentaenoic acid on stress response and immune function after a severely stressful operation. Ann Surg 229:255–261

    Google Scholar 

  23. Miles EA, Calder PC (1998) Modulation of immune function by dietary fatty acids. Proc Nutr Soc 57:277–292

    Google Scholar 

  24. Calder PC (1995) Fatty acids, dietary lipids and lymphocyte functions. Biochem Soc Trans 23:302–309

    Google Scholar 

  25. Calder PC (1998) Dietary fatty acids and the immune system. Nutr Rev 56:S70–S83

    Google Scholar 

  26. Calder PC (1996) Can n–3 polyunsaturated fatty acids be used as immunomodulatory agents? Biochem Soc Trans 24:211–220

    Google Scholar 

  27. Calder PC (1998) Fat chance of immunomodulation. Immunol Today 19:244–247

    Google Scholar 

  28. Calder PC (1996) Effects of fatty acids and dietary lipids on cells of the immune system. Proc Nutr Soc 55:127–150

    Google Scholar 

  29. Blok WL, Katan MB, van der Meer JW (1996) Modulation of inflammation and cytokine production by dietary (n–3) fatty acids. J Nutr 126:1515–1533

    Google Scholar 

  30. Calder PC, Newsholme EA (1992) Polyunsaturated fatty acids suppress human peripheral blood lymphocyte proliferation and interleukin-2 production. Clin Sci (Colch) 82:695–700

    Google Scholar 

  31. Purasiri P, McKechnie A, Heys SD, Eremin O (1997) Modulation in vitro of human natural cytotoxicity, lymphocyte proliferative response to mitogens and cytokine production by essential fatty acids. Immunology 92:166–172

    Google Scholar 

  32. 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. Clin Immunol Immunopathol 59:335–345

    Google Scholar 

  33. Kim DN, Schmee J, Thomas WA (199) Dietary fish oil added to a hyperlipidemic diet for swine results in reduction in the excessive number of monocytes attached to arterial endothelium. Atherosclerosis 81:209–216

    Google Scholar 

  34. Baldie G, Kaimakamis D, Rotondo D (1993) Fatty acid modulation of cytokine release from human monocytic cells. Biochim Biophys Acta 1179:125–133

    Google Scholar 

  35. Lee TH, Hoover RL, Williams JD, Sperling RI., Ravalese J III, Spur BW, Robinson DR, Corey EJ, Lewis RA, Austen KF (1985) Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 312:1217–1224

    Google Scholar 

  36. Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC, et al. (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. N Engl J Med 320:265–271

    Google Scholar 

  37. Goldyne ME (1988) Lymphocytes and arachidonic acid metabolism. Prog Allergy 44:140–152

    Google Scholar 

  38. Murphy FJ, Reen DJ (1996) Diminished production of prostaglandin E2 by monocytes of newborns is due to altered fatty acid membrane content and reduced cyclooxygenase activity. J Immunol 157:3116–3121

    Google Scholar 

  39. Irvine RF (1982) How is the level of free arachidonic acid controlled in mammalian cells? Biochem J 204:3–16

    Google Scholar 

  40. Suchner U, Senftleben U (1994) Immune modulation by polyunsaturated fatty acids during nutritional therapy: interactions with synthesis and effects of eicosanoids. Infusionsther Transfusionsmed 21:167–182

    Google Scholar 

  41. Tang DG, Porter AT, Honn KV (1997) Critical role of arachidonate lipoxygenases in regulating apoptosis. Adv Exp Med Biol 407:405–411

    Google Scholar 

  42. Yaqoob P (2003) Fatty acids as gatekeepers of immune cell regulation. Trends Immunol 24:639–645

    Google Scholar 

  43. Speizer LA, Watson MJ, Brunton LL (1991) Differential effects of omega-3 fish oils on protein kinase activities in vitro. Am J Physiol 261:E109–E114

    Google Scholar 

  44. Mirnikjoo B, Brown SE, Kim HFS, Marangell LB, Sweatt JD, Weeber EJ (2001) Protein kinase inhibition by omega−3 fatty acids. J Biol Chem 276:10888–10896

    Google Scholar 

  45. Jacobson MD, Burne JF, Raff MC (1994) Programmed cell death and Bcl-2 protection in the absence of a nucleus. Embo J 13:1899–1910

    Google Scholar 

  46. Couldwell WT, Hinton DR, Law RE (1994) Protein kinase C and growth regulation in malignant gliomas. Neurosurgery 35:1184–1186

    Google Scholar 

  47. Sessler AM, Ntambi JM (1998) Polyunsaturated fatty acid regulation of gene expression. J Nutr 128:923–926

    Google Scholar 

  48. Fernandes G, Troyer DA, Jolly CA (1998) The effects of dietary lipids on gene expression and apoptosis. Proc Nutr Soc 57:543–550

    Google Scholar 

  49. Drevon CA, Nenseter MS, Brude IR, Finstad HS, Kolset SO, Rustan AC (1995) Omega-3 fatty acids–nutritional aspects. Can J Cardiol 11:47G–54G

    Google Scholar 

  50. Das UN (1999) Essential fatty acids, lipid peroxidation and apoptosis. Prostaglandins Leukot Essent Fatty Acids 61:157–163

    Google Scholar 

  51. Avula CP, Fernandes G (1999) Modulation of antioxidant enzymes and apoptosis in mice by dietary lipids and treadmill exercise. J Clin Immunol 19:35–44

    Google Scholar 

  52. Buttke TM, Sandstrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15:7–10

    Google Scholar 

  53. Betteridge DJ (2000) What is oxidative stress? Metabolism 49:3–8

    Google Scholar 

  54. Um HD, Orenstein JM, Wahl SM (1996) Fas mediates apoptosis in human monocytes by a reactive oxygen intermediate dependent pathway. J Immunol 156:3469–3477

    Google Scholar 

  55. Garrido A, Garrido F, Guerra R, Valenzuela A (1989) Ingestion of high doses of fish oil increases the susceptibility of cellular membranes to the induction of oxidative stress. Lipids 24:833–835

    Google Scholar 

  56. Finstad HS, Drevon CA, Kulseth MA, Synstad AV, Knudsen E, Kolset SO (1998) Cell proliferation, apoptosis and accumulation of lipid droplets in U937-1 cells incubated with eicosapentaenoic acid. Biochem J 336:451–459

    Google Scholar 

  57. Finstad HS, Dyrendal H, Myhrstad MC, Heimli H, Drevon CA (200) Uptake and activation of eicosapentaenoic acid are related to accumulation of triacylglycerol in Ramos cells dying from apoptosis. J Lipid Res 41:554–563

    Google Scholar 

  58. Scorrano L, Penzo D, Petronilli V, Pagano F, Bernardi P (2000) Arachidonic acid causes cell death through the mitochondrial permeability transition. Implications for tumor necrosis factor-alpha aopototic signaling. J Biol Chem 27:27

    Google Scholar 

  59. Guidarelli A, Sestili P, Fiorani M, Cantoni O (2000) Arachidonic acid induces calcium-dependent mitochondrial formation of species promoting strand scission of genomic DNA. Free Radic Biol Med 28:1619–1627

    Google Scholar 

  60. Kong JY, Rabkin SW (2000) Palmitate-induced apoptosis in cardiomyocytes is mediated through alterations in mitochondria: prevention by cyclosporin A. Biochim Biophys Acta 1485:45–55

    Google Scholar 

  61. Listenberger LL, Ory DS, Schaffer JE (2001) Palmitate-induced apoptosis can occur through a ceramide-independent pathway. J Biol Chem 276:14890-14895

    Google Scholar 

  62. Sweeney B, Puri P, Reen DJ (2001) Polyunsaturated fatty acids influence neonatal monocyte survival. Pediatr Surg Int 17:254–258

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Children’s Research Centre, University College Dublin, Our Lady’s Hospital for Sick Children, Crumlin, Dublin, 12, Ireland

    Brian Sweeney, Prem Puri & Denis J. Reen

  2. Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Our Lady’s Hospital for Sick Children, Crumlin, Dublin, 12, Ireland

    Denis J. Reen & Denis J. Reen

Authors
  1. Brian Sweeney
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prem Puri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Denis J. Reen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Denis J. Reen.

Additional information

Supported by a Health Research Board Research Training Fellowship grant.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sweeney, B., Puri, P. & Reen, D.J. Modulation of immune cell function by polyunsaturated fatty acids. Ped Surgery Int 21, 335–340 (2005). https://doi.org/10.1007/s00383-005-1385-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00383-005-1385-x

Keywords

Search

Navigation