Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Jul;92(1):105–113. doi: 10.1172/JCI116537

Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment.

S N Meydani 1, A H Lichtenstein 1, S Cornwall 1, M Meydani 1, B R Goldin 1, H Rasmussen 1, C A Dinarello 1, E J Schaefer 1
PMCID: PMC293543  PMID: 8325975

Abstract

Reductions in dietary fat, saturated fat, and cholesterol have been recommended to reduce the risk of heart disease in our society. The effects of these modifications on human cytokine production and immune responses have not been well studied. 22 subjects > 40 yr of age were fed a diet approximating that of the current American (14.1% of calories as saturated fatty acids, [SFA], 14.5% monounsaturated fatty acids [MUFA], 6.1% [n-6] polyunsaturated fatty acids [PUFA], 0.8% [n-3] PUFA, and 147 mg cholesterol/1,000 calories) for 6 wk, after which time they consumed (11 in each group) one of the two low-fat, low-cholesterol, high-PUFA diets based on National Cholesterol Education Panel (NCEP) Step 2 recommendations (4.0-4.5% SFA, 10.8-11.6% MUFA, 10.3-10.5% PUFA, 45-61 mg cholesterol/1,000 calories) for 24 wk. One of the NCEP Step 2 diets was enriched in fish-derived (n-3) PUFA (low-fat, high-fish: 0.54% or 1.23 g/d eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] [121-188 g fish/d]) and the other low in fish-derived (n-3) PUFA (low-fat, low-fish [0.13% or 0.27 g/d EPA and DHA] [33 g fish/d]). Measurements of in vivo and in vitro indexes of immune responses were taken after each dietary period. Long-term feeding of low-fat, low-fish diet enriched in plant-derived PUFA increased blood mononuclear cell mitogenic response to the T cell mitogen Con A, IL-1 beta, and TNF production and had no effect on delayed-type hypersensitivity skin response, IL-6, GM-CSF, or PGE2 production. In contrast, the low-fat, high-fish diet significantly decreased the percentage of helper T cells whereas the percentage of suppressor T cells increased. Mitogenic responses to Con A and delayed-type hypersensitivity skin response as well as the production of cytokines IL-1 beta, TNF, and IL-6 by mononuclear cells were significantly reduced after the consumption of the low-fat, high-fish diet (24, 40, 45, 35, and 34%, respectively; P < 0.05 by two-tailed Student's t test except for IL-1 beta and TNF, which is by one-tailed t test). Our data are consistent with the concept that the NCEP Step 2 diet that is high in fish significantly decreases various parameters of the immune response in contrast to this diet when it is low in fish. Such alterations may be beneficial for the prevention and treatment of atherosclerotic and inflammatory diseases but may be detrimental with regard to host defense against invading pathogens.

Full text

PDF
105

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barone J., Hebert J. R., Reddy M. M. Dietary fat and natural-killer-cell activity. Am J Clin Nutr. 1989 Oct;50(4):861–867. doi: 10.1093/ajcn/50.4.861. [DOI] [PubMed] [Google Scholar]
  2. Berdanier C. D., Johnson B., Hartle D. K., Crowell W. Life span is shortened in BHE/cdb rats fed a diet containing 9% menhaden oil and 1% corn oil. J Nutr. 1992 Jun;122(6):1309–1317. doi: 10.1093/jn/122.6.1309. [DOI] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Pober J. S., Majeau G. R., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med. 1984 Aug 1;160(2):618–623. doi: 10.1084/jem.160.2.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bevilacqua M. P., Pober J. S., Wheeler M. E., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 1985 Nov;76(5):2003–2011. doi: 10.1172/JCI112200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bieri J. G., Tolliver T. J., Catignani G. L. Simultaneous determination of alpha-tocopherol and retinol in plasma or red cells by high pressure liquid chromatography. Am J Clin Nutr. 1979 Oct;32(10):2143–2149. doi: 10.1093/ajcn/32.10.2143. [DOI] [PubMed] [Google Scholar]
  6. Chandra R. K. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet. 1992 Nov 7;340(8828):1124–1127. doi: 10.1016/0140-6736(92)93151-c. [DOI] [PubMed] [Google Scholar]
  7. Chang H. R., Dulloo A. G., Vladoianu I. R., Piguet P. F., Arsenijevic D., Girardier L., Pechère J. C. Fish oil decreases natural resistance of mice to infection with Salmonella typhimurium. Metabolism. 1992 Jan;41(1):1–2. doi: 10.1016/0026-0495(92)90181-9. [DOI] [PubMed] [Google Scholar]
  8. D'Ambola J. B., Aeberhard E. E., Trang N., Gaffar S., Barrett C. T., Sherman M. P. Effect of dietary (n-3) and (n-6) fatty acids on in vivo pulmonary bacterial clearance by neonatal rabbits. J Nutr. 1991 Aug;121(8):1262–1269. doi: 10.1093/jn/121.8.1262. [DOI] [PubMed] [Google Scholar]
  9. Dinarello C. A., Lonnemann G., Maxwell R., Shaldon S. Ultrafiltration to reject human interleukin-1-inducing substances derived from bacterial cultures. J Clin Microbiol. 1987 Jul;25(7):1233–1238. doi: 10.1128/jcm.25.7.1233-1238.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dupont J., White P. J., Carpenter M. P., Schaefer E. J., Meydani S. N., Elson C. E., Woods M., Gorbach S. L. Food uses and health effects of corn oil. J Am Coll Nutr. 1990 Oct;9(5):438–470. doi: 10.1080/07315724.1990.10720403. [DOI] [PubMed] [Google Scholar]
  11. Dyerberg J., Bang H. O. Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet. 1979 Sep 1;2(8140):433–435. doi: 10.1016/s0140-6736(79)91490-9. [DOI] [PubMed] [Google Scholar]
  12. Endres S., Ghorbani R., Kelley V. E., Georgilis K., Lonnemann G., van der Meer J. W., Cannon J. G., Rogers T. S., Klempner M. S., Weber P. C. 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 Feb 2;320(5):265–271. doi: 10.1056/NEJM198902023200501. [DOI] [PubMed] [Google Scholar]
  13. Endres S., Ghorbani R., Lonnemann G., van der Meer J. W., Dinarello C. A. Measurement of immunoreactive interleukin-1 beta from human mononuclear cells: optimization of recovery, intrasubject consistency, and comparison with interleukin-1 alpha and tumor necrosis factor. Clin Immunol Immunopathol. 1988 Dec;49(3):424–438. doi: 10.1016/0090-1229(88)90130-4. [DOI] [PubMed] [Google Scholar]
  14. Erickson K. L. Dietary fat modulation of immune response. Int J Immunopharmacol. 1986;8(6):529–543. doi: 10.1016/0192-0561(86)90023-8. [DOI] [PubMed] [Google Scholar]
  15. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  16. Goodwin J. S., Webb D. R. Regulation of the immune response by prostaglandins. Clin Immunol Immunopathol. 1980 Jan;15(1):106–122. doi: 10.1016/0090-1229(80)90024-0. [DOI] [PubMed] [Google Scholar]
  17. Hebert J. R., Barone J., Reddy M. M., Backlund J. Y. Natural killer cell activity in a longitudinal dietary fat intervention trial. Clin Immunol Immunopathol. 1990 Jan;54(1):103–116. doi: 10.1016/0090-1229(90)90010-n. [DOI] [PubMed] [Google Scholar]
  18. Hildes J. A., Schaefer O. The changing picture of neoplastic disease in the western and central Canadian Arctic (1950-1980). Can Med Assoc J. 1984 Jan 1;130(1):25–32. [PMC free article] [PubMed] [Google Scholar]
  19. Hubbard N. E., Somers S. D., Erickson K. L. Effect of dietary fish oil on development and selected functions of murine inflammatory macrophages. J Leukoc Biol. 1991 Jun;49(6):592–598. doi: 10.1002/jlb.49.6.592. [DOI] [PubMed] [Google Scholar]
  20. Johnston D. V., Marshall L. A. Dietary fat, prostaglandins and the immune response. Prog Food Nutr Sci. 1984;8(1-2):3–25. [PubMed] [Google Scholar]
  21. Kramer T. R., Schoene N., Douglass L. W., Judd J. T., Ballard-Barbash R., Taylor P. R., Bhagavan H. N., Nair P. P. Increased vitamin E intake restores fish-oil-induced suppressed blastogenesis of mitogen-stimulated T lymphocytes. Am J Clin Nutr. 1991 Nov;54(5):896–902. doi: 10.1093/ajcn/54.5.896. [DOI] [PubMed] [Google Scholar]
  22. Kremer J. M., Jubiz W., Michalek A., Rynes R. I., Bartholomew L. E., Bigaouette J., Timchalk M., Beeler D., Lininger L. Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study. Ann Intern Med. 1987 Apr;106(4):497–503. doi: 10.7326/0003-4819-106-4-497. [DOI] [PubMed] [Google Scholar]
  23. Lesourd B. M., Wang A., Moulias R. Serial delayed cutaneous hypersensitivity skin testing with multiple recall antigens in healthy volunteers: booster effect study. Ann Allergy. 1985 Nov;55(5):729–735. [PubMed] [Google Scholar]
  24. Libby P., Warner S. J., Friedman G. B. Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest. 1988 Feb;81(2):487–498. doi: 10.1172/JCI113346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McCosh E. J., Meyer D. L., Dupont J. Radioimmunoassay of prostaglandins E1, E2, and F2alpha in unextracted plasma, serum and myocardium. Prostaglandins. 1976 Oct;12(4):471–486. doi: 10.1016/0090-6980(76)90028-9. [DOI] [PubMed] [Google Scholar]
  26. Meydani M., Natiello F., Goldin B., Free N., Woods M., Schaefer E., Blumberg J. B., Gorbach S. L. Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women. J Nutr. 1991 Apr;121(4):484–491. doi: 10.1093/jn/121.4.484. [DOI] [PubMed] [Google Scholar]
  27. Meydani S. N., Endres S., Woods M. M., Goldin B. R., Soo C., Morrill-Labrode A., Dinarello C. A., Gorbach S. L. Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr. 1991 Apr;121(4):547–555. doi: 10.1093/jn/121.4.547. [DOI] [PubMed] [Google Scholar]
  28. Meydani S. N., Lichtenstein A. H., White P. J., Goodnight S. H., Elson C. E., Woods M., Gorbach S. L., Schaefer E. J. Food use and health effects of soybean and sunflower oils. J Am Coll Nutr. 1991 Oct;10(5):406–428. doi: 10.1080/07315724.1991.10718168. [DOI] [PubMed] [Google Scholar]
  29. Meydani S. N., Shapiro A. C., Meydani M., Macauley J. B., Blumberg J. B. Effect of age and dietary fat (fish, corn and coconut oils) on tocopherol status of C57BL/6Nia mice. Lipids. 1987 May;22(5):345–350. doi: 10.1007/BF02534004. [DOI] [PubMed] [Google Scholar]
  30. Meydani S. N., Yogeeswaran G., Liu S., Baskar S., Meydani M. Fish oil and tocopherol-induced changes in natural killer cell-mediated cytotoxicity and PGE2 synthesis in young and old mice. J Nutr. 1988 Oct;118(10):1245–1252. doi: 10.1093/jn/118.10.1245. [DOI] [PubMed] [Google Scholar]
  31. Nachman R. L., Hajjar K. A., Silverstein R. L., Dinarello C. A. Interleukin 1 induces endothelial cell synthesis of plasminogen activator inhibitor. J Exp Med. 1986 Jun 1;163(6):1595–1600. doi: 10.1084/jem.163.6.1595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nawroth P. P., Stern D. M. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med. 1986 Mar 1;163(3):740–745. doi: 10.1084/jem.163.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Payan D. G., Wong M. Y., Chernov-Rogan T., Valone F. H., Pickett W. C., Blake V. A., Gold W. M., Goetzl E. J. Alterations in human leukocyte function induced by ingestion of eicosapentaenoic acid. J Clin Immunol. 1986 Sep;6(5):402–410. doi: 10.1007/BF00915380. [DOI] [PubMed] [Google Scholar]
  34. Roberts-Thomson I. C., Whittingham S., Youngchaiyud U., Mackay I. R. Ageing, immune response, and mortality. Lancet. 1974 Aug 17;2(7877):368–370. doi: 10.1016/s0140-6736(74)91755-3. [DOI] [PubMed] [Google Scholar]
  35. Schindler R., Mancilla J., Endres S., Ghorbani R., Clark S. C., Dinarello C. A. Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood. 1990 Jan 1;75(1):40–47. [PubMed] [Google Scholar]
  36. Shapiro A. C., Wu D., Meydani S. N. Eicosanoids derived from arachidonic and eicosapentaenoic acids inhibit T cell proliferative response. Prostaglandins. 1993 Mar;45(3):229–240. doi: 10.1016/0090-6980(93)90049-d. [DOI] [PubMed] [Google Scholar]
  37. Stenson W. F., Cort D., Rodgers J., Burakoff R., DeSchryver-Kecskemeti K., Gramlich T. L., Beeken W. Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med. 1992 Apr 15;116(8):609–614. doi: 10.7326/0003-4819-116-8-609. [DOI] [PubMed] [Google Scholar]
  38. Warner S. J., Libby P. Human vascular smooth muscle cells. Target for and source of tumor necrosis factor. J Immunol. 1989 Jan 1;142(1):100–109. [PubMed] [Google Scholar]
  39. Wayne S. J., Rhyne R. L., Garry P. J., Goodwin J. S. Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. J Gerontol. 1990 Mar;45(2):M45–M48. doi: 10.1093/geronj/45.2.m45. [DOI] [PubMed] [Google Scholar]
  40. Yoshino S., Ellis E. F. Effect of a fish-oil-supplemented diet on inflammation and immunological processes in rats. Int Arch Allergy Appl Immunol. 1987;84(3):233–240. doi: 10.1159/000234429. [DOI] [PubMed] [Google Scholar]
  41. van der Meer J. W., Endres S., Lonnemann G., Cannon J. G., Ikejima T., Okusawa S., Gelfand J. A., Dinarello C. A. Concentrations of immunoreactive human tumor necrosis factor alpha produced by human mononuclear cells in vitro. J Leukoc Biol. 1988 Mar;43(3):216–223. doi: 10.1002/jlb.43.3.216. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES