Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men


This study was conducted to determine the effects of arachidonic acid (AA) supplementation on human immune response (IR) and on the secretion of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). Ten healthy men (20–38 yr) participated in the study and lived at the Metabolic Suite of the Western Human Nutrition Research Center. They were fed a basal diet (57, 27, and 16 energy percentage from carbohydrate, fat, and protein, respectively, and AA 200 mg/d) for the first 15 d of the study. Additional AA (1.5 g/d) was added to the diet of six men from day 16 to 65, while the remaining four subjects remained on the basal diet. The diets of the two groups were crossed-over from day 66 to 115. In vitro indices of IR were examined using blood drawn on days 15, 58, 65, 108, and 115. Influenza antibody titers were determined in the sera prepared from blood drawn on days 92 and 115 (23 d postimmunization). AA supplementation caused significant increases in the in vitro secretion of LTB4, and PGE2, but it did not alter the in vitro secretion of tumor necrosis factor α; interleukins 1β, 2, 6; and the receptor for interleukin 2. Nor did it change the number of circulting lymphocytes bearing markers for specific subsets (B, T, helper, suppressor, natural killer) and the serum antibody titers against influenza vaccine. The opposing effects of PGE2 and LTB4 may have led to the lack of change in immune functions tested.

This is a preview of subscription content, access via your institution.



arachidonic acid




immune response


linoleic acid




leukotriene B4


natural killer


peripheral blood mononuclear cells


prostaglandin E




polyunsaturated fatty acids


  1. 1.

    Mertin, J., and Hughes, D. (1975) Specific Inhibitory Action of Polyunsaturated Fatty Acids on Lymphocyte Transformation Induced by PHA and PPD, Int. Arch. Allergy Appl. Immunol. 48, 203–210.

    PubMed  CAS  Google Scholar 

  2. 2.

    Weyman, C., Morgan, S.J., Belin, J., and Smith, A.D. (1977) Phytohemagglutinin Stimulation of Human Lymphocytes. Effects of Fatty Acids on Uridine Uptake and Phosphoglyceride Fatty Acid Profile, Biochim. Biophys. Acta 496, 155–166.

    PubMed  CAS  Google Scholar 

  3. 3.

    Chow, S.C., Sisfontes, L., Bjorkhem, I., and Jandal, M. (1989) Suppression of Growth in a Leukemic T Cell Line by n−3 and n−6 Polyunsaturated Fatty Acids, Lipids 24, 700–704.

    PubMed  CAS  Google Scholar 

  4. 4.

    Lockniskar, M., Nauss, K.M., and Newberne, PM. (1983) The Effect of Quality and Quantity of Dietary Fat on the Immune System, J. Nutr. 113, 951–961.

    Google Scholar 

  5. 5.

    Marshall, L.A., and Johnston, P.V. (1985) The Influence of Dietary Essential Fatty Acids on Rat Immunocompetent Cell Prostaglandin Synthesis and Mitogen Induced Blastogenesis, J. Nutr. 115, 1572–1580.

    PubMed  CAS  Google Scholar 

  6. 6.

    Krammer, T.R., Briske-Anderson, M., Johnson, S.B., and Holman, R.T. (1986) Influences of Dietary Polyunsaturated and Saturated Fats and of Concanavalin A upon Proliferation of Spleen Lymphoid Cells from Rats, Nutr. Res. 6, 1219–1227.

    Article  Google Scholar 

  7. 7.

    Fritsche, K.L., Cassity, N.A., and Huang, S.C. (1991) Effects of Dietary Fat Sources on Antibody Production and Lymphocyte Proliferation in Chickens, Poult. Sci. 70, 611–617.

    PubMed  CAS  Google Scholar 

  8. 8.

    Osmann, J.B., Erickson, K.L., and Canolty, N.L. (1985) Effects of Saturation and Concentration of Dietary Fats on Lymphocyte Transformation in Mice, Nutr. Rep. Intl. 22, 279–284.

    Google Scholar 

  9. 9.

    Thomas, J.K., and Erickson, K.L. (1985) Dietary Fatty Acid Modulation of Murine T-Cell Responses in vivo, J. Nutr. 115, 1528–1534.

    PubMed  CAS  Google Scholar 

  10. 10.

    Kelley, D.S., Nelson, G.J., Serrato, C.M., Schmidt, P.C., and Branch, L.B. (1988) Effects of Type of Dietary Fat on Indices of Immune Status in Rabbits, J. Nutr. 118, 1376–1384.

    PubMed  CAS  Google Scholar 

  11. 11.

    Kelley, D.S., Branch, L.B., and Iacono, J.M. (1989) Nutritional Modulation of Human Immune System, Nutr. Res. 9, 965–975.

    CAS  Article  Google Scholar 

  12. 12.

    Kelley, D.S., Dougherty, R.M., Branch, L.B., Taylor, P.C., and Iacono, J.M. (1952) Concentration of Dietary n−6 Polyunsaturated Fatty Acids and the Human Immune Status, Clin. Immunol. Immunopathol. 62, 240–244.

    Article  Google Scholar 

  13. 13.

    Barone, J., Hebert, J.R., and Reddy, M.M. (1989) Dietary Fat and Natural Killer-Cell Activity, Am. J. Clin. Nutr. 50, 861–867.

    PubMed  CAS  Google Scholar 

  14. 14.

    Rasmussen, L.B., Kiens, B., Pederson, B.K., and Richter, E.A. (1994) Effect of Diet and Plasma Fatty Acid Composition on Immune Status of Elderly Men, Am. J. Clin. Nutr. 59, 572–577.

    PubMed  CAS  Google Scholar 

  15. 15.

    Gualde, N., Atluru, D., and Goodwin, J.S. (1985) Effect of Lipooxygenase Metabolites of Arachidonic Acid on Proliferation of Human T Cells Subsets, J. Immunol. 134, 1125–1129.

    PubMed  CAS  Google Scholar 

  16. 16.

    Kunkel, S.L., and Chensue, S.W. (1986) The Role of Arachidonic Acid Metabolites in Mononuclear Phagocytic Cell Interactions, Int. J. Dermatol. 25, 83–89.

    PubMed  CAS  Google Scholar 

  17. 17.

    Saigh, S., Rigal, D., and Monier, J.C. (1994) Effects of PGE2 upon Differentiation and Programmed Cell Death of Suspension Cultured CD4-CD8-Thymocytes, Int. J. Immunopharmacol. 16, 775–786.

    Article  Google Scholar 

  18. 18.

    Rola-Pleszcynski, M., and Lemaire, I. (1985) Leukotrienes Augment Interleukin 1 Production by Human Monocytes, J. Immunol., 135, 3958–3961.

    Google Scholar 

  19. 19.

    Monick, M., Glazier, J., and Hunninghake, G.W. (1987) Human Alveolar Macrophages Suppress IL-1 Activity via the Secretion of Prostaglandin E2, Am. Rev. Respir. Dis. 135, 72–77.

    PubMed  CAS  Google Scholar 

  20. 20.

    Kumar, G.S., and Das, U.N. (1994) Effect of Prostaglandins and Their Precursors on the Proliferation of Human Lymphocytes and Their Secretion of Tumor Necrosis Factor and Various Interleukins, Prostaglandins Leukotrienes Essent. Fatty Acids 50, 331–334.

    CAS  Article  Google Scholar 

  21. 21.

    Joulain, C., Meskini, M., Anker, G., Lagarde, M., and Prigent, A.F. (1995) Esterification of 12(S)-Hydroxy-5,8,10,14-eicosatetraenoic Acid into Phospholipids of Human Peripheral Blood Mononuclear Cells: Inhibition of the Proliferative Response, J. Cell Physiol. 164, 154–163.

    PubMed  CAS  Article  Google Scholar 

  22. 22.

    Kinsella, J.E., Lokesh, B., Broughton, S., and Whelan, J. (1990) Dietary Polyunsaturated Fatty Acids and Eicosanoids: Potential Effects on the Modulation of Inflammatory and Immune Cells: An Overview, Nutrition 6, 24–44.

    PubMed  CAS  Google Scholar 

  23. 23.

    Joulain, C., Guichardant, M., Lagarde, M., and Prigent, A.F. (1995) Influence of Polyunsaturated Fatty Acids on Lipid Metabolism in Human Mononuclear Cells and Early Biochemical Events Associated with Lymphocyte Activation, J. Lipid Mediat. Cell Signal 11, 63–79.

    PubMed  CAS  Article  Google Scholar 

  24. 24.

    Rotondo, D., Earl, C.R., Laing, K.J., and Kaimakamis, D. (1994) Inhibition of Cytokine-Stimulated Thymic Lymphocyte Proliferation by Fatty Acids: The Role of Eicosanoids, Biochim. Biophys. Acta. 1223, 185–194.

    PubMed  CAS  Article  Google Scholar 

  25. 25.

    Santoli, D., Phillips, P.D., Colt, T.L., and Zurier, R.B. (1990) Suppression of IL 2-Dependent Cell Growth in vitro by Prostaglandin E (PGE) and Their Precursor Fatty Acids. Evidence for a PGE-Independent Mechanism of Inhibition by the Fatty Acids, J. Clin. Invest. 85, 424–432.

    PubMed  CAS  Article  Google Scholar 

  26. 26.

    Calder, P.C., Bevan, S.J., and Newsholme, E.A. (1992) The Inhibition of T-Lymphocyte Proliferation by Fatty Acids Is via an Eicosanoid Independent Mechanism, Immunology 75, 108–115.

    PubMed  CAS  Google Scholar 

  27. 27.

    Ceuppens, J.L., and Desmyter, J. (1987) Effect of Prostaglandin Synthesis Inhibition in vivo on the Immune Response Following Hepatitis B Vaccination in Normal Subjects, Intl. J. Immunopharmacol. 9, 803–810.

    CAS  Article  Google Scholar 

  28. 28.

    Kelley, D.S., Taylor, P.C., Nelson, G.J., Schmidt, P.C., Mackey, B.E., and Kyle, D. (1997) Effects of Dietary Arachidonic Acid on Human Immune Response, Lipids 32, 449–456.

    PubMed  CAS  Google Scholar 

  29. 29.

    Kelley, D.S., Daudu, P.A., Taylor, P.C., Mackey, B.E., and Turnlund, J.R. (1995) Effects of Low-Copper Diets on Human Immune Response, Am. J. Clin. Nutr. 62, 412–416.

    PubMed  CAS  Google Scholar 

  30. 30.

    Hierholzer, J.C., Suggs, M.T., and Hall, E.C. (1969) Standardized Viral Hemagglutination and Hemagglutination Tests. II Description and Statistical Evaluation, Appl. Microbiol. 18, 824–833.

    PubMed  CAS  Google Scholar 

  31. 31.

    SAS Institute Inc. SAS/STATTM (1987) Guide for Personal Computers, version 6th edn., SAS Institute Inc., Cary.

    Google Scholar 

  32. 32.

    Ferretti, A., Nelson, G.J., Schmidt, P.C., Kelley, D.S., Bartolini, G., and Flanagan, V.P. (1997) Increased Dietary Arachidonic Acid Enhances the Synthesis of Vasoactive Eicosanoids in Humans, Lipids 32, 435–439.

    PubMed  CAS  Google Scholar 

  33. 33.

    Sinclair, A.J., and Mann, N.J. (1996) Short-Term Diets Rich in Arachidonic Acid Influence Plasma Phospholipid Polyunsaturated Fatty Acid Levels and Prostacyclin and Thromboxane Production in Humans, J. Nutr. 126, 1110S-1114S.

    PubMed  CAS  Google Scholar 

  34. 34.

    Seyberth, H.W., Oelz, O., Kennedy, T., Sweetman, B.J., Dannon, A., Frolich, J.C., Heimberg, M., and Otes, J.A. (1975) Increased Arachidonic Acid in Lipids After Administration to Men: Effects on Prostaglandin Biosynthesis, Clin. Pharmacol. Ther. 18, 521–529.

    PubMed  CAS  Google Scholar 

  35. 35.

    Blair, I.A., Prakash, C., Dougherty, M.A., and Iacono, J.M. (1993) Dietary Modification of Omega 6 Fatty Acid Intake and Its Effect on Urinary Eicosanoid Excretion, Am. J. Clin. Nutr. 57, 154–160.

    PubMed  CAS  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Darshan S. Kelley.

About this article

Cite this article

Kelley, D.S., Taylor, P.C., Nelson, G.J. et al. Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men. Lipids 33, 125–130 (1998).

Download citation


  • Arachidonic Acid
  • PGE2
  • Antibody Titer
  • Eicosanoid
  • Basal Diet