Skip to main content
SpringerLink
Log in

Dietary modulation of the immune response in the aged

  • Published:
AGE Aims and scope Submit manuscript

Abstract

The age-associated changes of the immune response are well documented. However, the biochemical changes leading to these alterations are not well-defined. A series of experiments using dietary antioxidants and prooxidants were conducted in old mice and older adults to determine the contribution of lipid peroxides, especially that of oxidative products of arachidonic acid in the age-associated decline of the immune response. Splenocytes from old mice and peripheral blood mononuclear cells (PBMC) from older adults produced significantly more PGE2 and their plasma had higher TBAR levels than their young counterparts. Vitamin E supplementation of both old mice and older adults decreased PGE2 synthesis while increasing IL-2 production, mitogenic response to Con A and the delayed hypersensitivity skin test (DTH). Older adults supplemented with vitamin E showed a significant reduction in plasma TBAR. Supplementation with another dietary antioxidant, glutathione (GSH) (0.1 to 1% by wt of diet for 4 wk), significantly improved a mitogenic response to Con A and PHA and DTH to DNFB in 17 and 24 mo old mice. This effect was due to an increase in spleen GSH level and not to a change in PGE2 synthesis. On the other hand, supplementation of older women with fish oil containing highly unsaturated n-3 fatty acids, EPA and DHA (2.4 g/day for 3 mo) decreased cytokine production (IL-1, IL-2, IL-6, TNF), mitogenic response of PBMC to PHA and their production of PGE2. Thus, supplementation with dietary antioxidants increases and with dietary prooxidants decreases immune responsiveness of aged. These effects are mediated via changes in the formation of PGE2 and other lipid peroxides.

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. Siskind, G.W.: Immunological aspects of aging: an overview, in Biological Mechanisms in Aging, edited by Schimke, R.T., USDA, NIH, 1980, pp. 455–467.

  2. Roberts-Thompson, I.C., Yvonschaiyud, V., and Whittingham, S.: Aging, immune response and mortality. Lancet, II: 368–370, 1974.

    Article  Google Scholar 

  3. Wayne, S.J., Rhyne, R.L., Garry, P.J., and Goodwin, J.S.: Cell-mediated immunity as a predictor of morbidity and mortality in the aged. J. Gerontol. Med. Sci., 45: M45–48, 1990.

    Article  CAS  Google Scholar 

  4. Marrie, T.J., Johnson, S., and Durant, H.: Cell-mediated immunty of healthy adult Nova Scotians in various age groups compared with nursing home and hospitalized senior citizens. J. Allergy Clin. Immunol,. 81: 836–844, 1988.

    Article  PubMed  CAS  Google Scholar 

  5. Larsson, J., Unosson, M., Ek, A.C., Nilsson, L., Thorslund, S., and Bjurulf, P.: Effect of dietary supplement on nutritional status and clinical outcome in 501 geriatric patients — a randomised study. Clin. Nutr., 9: 179–184, 1990.

    Article  PubMed  CAS  Google Scholar 

  6. Keutsch, G.T., Wilson, C.S., and Waksal, S.D.: Nutrition, host defenses and the lymphoid system. Adv. Host. Def. Mech., 2: 257–306, 1983.

    Google Scholar 

  7. Chandra, S., and Chandra, R.K.: Nutrition, immune response and outcome. Prog. Food. Nutr. Sci., 10: 1–65, 1986.

    PubMed  CAS  Google Scholar 

  8. Meydani, S.N., and Blumberg, J.B.: Nutrition and the immune function in the elderly, in Human Nutrition: A Comprehensive Treatise, Vol. VII, edited by Munro, H. and Danforth, D.E., New York, Plenum Press, 1989, pp. 61–87.

    Google Scholar 

  9. Meydani, S.: Micronutrients and immune function in the elderly. NY Acad. Sci., 587: 196–207, 1990.

    CAS  Google Scholar 

  10. Meydani, S.N., Barklund, M.P., Liu, S., Meydani, M., Miller, R., Cannon, J., Morrow, F., Rocklin, R., and Blumberg, J.: Vitamin E supplementation enhances cell-mediated immunity in healthy elderly. Am. J. Clin. Nutr., 52: 557–563, 1990.

    PubMed  CAS  Google Scholar 

  11. Kennes, B., Dumont, I., Brohee, D., Hubert, C., and Neve, P.: Effect of vitamin C supplementation on cell-mediated immunity in old people. Gerontol., 29: 305–310, 1983.

    Article  CAS  Google Scholar 

  12. Talbott, M.C., Miller, L.T., and Kerkvliet, N.: Pyridoxine supplementation: effect of lyphocyte response in elderly persons. Am. J. Clin. Nutr., 46: 569–664, 1987.

    Google Scholar 

  13. Meydani, S.N., Ribaya-Mercado, J.D., Russell, R.M., Sahyoun, N., Morrow, F.D., and Gershoff, S.N.: The effect of vitamin B6 on the immune response of healthy elderly. NY Acad. Sci., 587: 303–306, 1990.

    Google Scholar 

  14. Wagner, P.A., Jernigan, J.A., Baily, L.B., Nickens, C., and Brazzi G.A.: Zinc nutriture and cell mediated immunity in the aged. Int. J. Vltam. Nutr. Res., 53: 94–101, 1983.

    CAS  Google Scholar 

  15. Duchateau, J., Delepesse, G., Vrijens, R., and Collet, H.: Beneficial effects of oral zinc supplementation on the immune response of old people. Am. J. Med., 70: 1001–1004, 1981.

    Article  PubMed  CAS  Google Scholar 

  16. Bogden, J.D., Oleske, J.M., Lavenhar, M.A., Munves, E.M., Kemp, F.W., Bruening, K.S., Holding, K.J., Denny, T.N., Guarino, M.A., Krieger, L.M., and Holland, B.K.: Zinc and immunocompetence in elderly people: effects of zinc supplementation for 3 months. Am. J. Clin. Nutr., 48: 655–6636, 1988.

    PubMed  CAS  Google Scholar 

  17. Bogden, J.C., Oleske, J.M., Lavenhar, M.A., Munves, E.M., Kemp, F.W., Bruening, K.S., Holding, K.J., Denny, T.N., Guarino, M.A., Krieger, L.M., and Holland, B.K.: Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly. J. Am. Coll. Nutr., 9: 214–225, 1990.

    PubMed  CAS  Google Scholar 

  18. Chavance, M., Brubacher, G., Herberth, B., Vernhes, G., Mistacki, T., Dete, F., Fournier, C., and Janot, C.: Immunological and nutritional status among the elderly, in Nutrition, Immunity, and Illness in the Elderly, edited by Chandra, R.K., New York, Pergamon Press, 1985, pp. 137–142.

    Google Scholar 

  19. Menkes, M., Comstock, G., Vuilleumier, J., Helsing, K., Rider, A., and Brookmezer, R.: Serum beta-carotene, vitamins A and E, selenium, and risk of lung cancer. N. Engl. J. ed, 315: 1250–1254, 1986.

    Article  CAS  Google Scholar 

  20. Block, G.: Vitamin C and cancer prevention: the epidemiologic evidence. Am. J. Clin. Nutr., 53: 270S–282S, 1991.

    PubMed  CAS  Google Scholar 

  21. Knekt, P., Aromaa, A., Maatela, J., Aaran, R., Nikkari, T., Hakama, M., Hakulinen, T., Peto, R., Saxen, E., and Teppo, L.: Serum vitamin E and risk of cancer among Finnish men during a ten-year follow-up. Am. J. Epidemiol., 127: 28–41, 1988.

    PubMed  CAS  Google Scholar 

  22. Willett, W.C., Polk, B.F., Underwood, B., Stampfer, M.J., Pressel, S., Rosner, B., Taylor, J.O., Scheider, K., and Hames, C.G.: Relation of serum vitamins A and E and carotenoids to the risk of cancer. New Engl. J. Med., 310: 430–34, 1984.

    Article  PubMed  CAS  Google Scholar 

  23. Tengerdy, R.P., Heinzerling, R.H., and Mathias, M.M.: Effect of vitamin E on disease resistance and immune responses, in Tocopherol, Oxygen, and Biomembranes, edited by de Duve, C. and Hayaiski, O., Amsterdam, Elsevier/North Holland Biomedical Press, 1978, pp. 191–200.

    Google Scholar 

  24. Tengerdy, R.P., Mathias, M.M., and Nockels, C.F.: Effect of vitamin E on immunity and disease resistance, in Vitamins, Nutrition and Cancer, edited by Prasad, A., Basel, Krager, 1984, pp. 123–133.

    Google Scholar 

  25. Meydani, S.N., Endres, S., Woods, M.M., Goldin, B.R., Soo, C., Morrill-Labrode, A., Dinarello, C.A., and Gorbach, S.L. Oral N-3 fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison in young and older women. J. Nutr., 121: 547–555, 1991.

    PubMed  CAS  Google Scholar 

  26. Pubelle, P., Chantreuil, J., Bensadous, J., Blotman, F., Simon, L., and Crastes de Paule, A.: Plasma lipoperoxides and aging. Biomed., 36: 164–6, 1982.

    Google Scholar 

  27. Yagi, K.: Assay for serum lipid peroxide level and its clinical significance, in Lipid Peroxides in Biology and Medicine, edited by Yagi, K., New York, Academic Press, 1982, pp. 223–242.

    Google Scholar 

  28. Kay, M.M.B.: An overview of immune aging. Mech. Ageing Dev., 9: 39–59, 1978.

    Article  Google Scholar 

  29. Hallgren, H.M., Buckley, C.E., Gilbertsen, V.A., and Yunis, E.J.: Lymphocyte phytohemagglutinin responsiveness, immunoglobulins and autoantibodies in aging humans. J. Immunol., 4: 1101–1111, 1973.

    Google Scholar 

  30. Buckley, C.G., Buckley, E.G., and Dorsey, F.C.: Longitudinal changes in serum immunoglobulin levels in older humans. Fed. Proc., 33: 2036–2039, 1974.

    PubMed  CAS  Google Scholar 

  31. Makinodan, T.: Cellular basis of immunologic aging, in Biologic Mechanisms in Aging, edited by Schimke, R.T., USDA, NIH, 1981, pp. 488–500.

  32. Goodwin, J.S., Searles, R.P., and Tung, K.S.K.: Immunological responses of a healthy elderly population. Clin. Exp. Immunol., 48: 403–410, 1982.

    PubMed  CAS  Google Scholar 

  33. Thoman, M.L., and Weigle, W.O.: Lymphokines and aging: Interleukin-2 production and activity in aged animals. J. Immunol., 127: 2101–2106, 1981.

    Google Scholar 

  34. Miller, R.A., and Stutman, O.: Decline in aging mice of anti-TNP cytotoxic T cell response attributable to loss of lyt-2-IL-2 producing helper cell function. Eur. J. Immunol., 11: 751–756, 1981.

    PubMed  CAS  Google Scholar 

  35. Chang, M.P., Makinodan, T., Peterson, W.J., and Strehler, B.L.: Role of T cells and adherent cells in age-related decline in murine interleukin 2 production. J. Immunol., 129: 2426–2430, 1982.

    PubMed  CAS  Google Scholar 

  36. Gillis, S., Kozak, R., Durante, M., and Menkler, M.K.: Immunological studies of aging. Decreased production of and response to T cell growth factor by lymphocytes from aged humans. J. Clin. Invest., 67: 937–942, 1982.

    Google Scholar 

  37. Thoman, M.L., and Weigle, W.O.: Reconstitution of in vivo cell-mediated lympholysis response in aged mice with interleukin 2. J. Immunol., 134: 949–952, 1981.

    Google Scholar 

  38. Nagel, J.E., Chopra, R.K., Chrest, F.J., et al.: Decreased proliferation, interleukin 2 synthesis and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors. J. Clin. Invest., 81: 1096–1101, 1988.

    Article  PubMed  CAS  Google Scholar 

  39. Bash, J.A.: Cellular immunosenescence in F344 rats; decline in responsiveness to phytohemagglutinin involves changes in both T cells and macrophages. Mech. Aging Devel., 21: 321–333, 1983.

    Article  CAS  Google Scholar 

  40. Meydani, S.N., Meydani, M., Verdon, C.P., Shapiro, A.C., Blumberg, J.B., and Hayes, K.C.: Vitamin E supplementation suppresses prostaglandin E2 synthesis and enhances the immune response in aged mice. Mech. Ageing Dev., 34: 191–201, 1986a.

    Article  PubMed  CAS  Google Scholar 

  41. Bartocci, A., Maggi, F.M., Welker, R.D., and Veronese, F.: Age-related immunosuppression: putative role of prostaglandins, in Prostaglandins and Cancer, edited by Powles, T.J., Backman, R.S., Honn, K.V., Ramwell, P., New York, Alan R. Liss, 1982, pp. 725–730.

    Google Scholar 

  42. Rosenstein, M.M., and Strauser, H.R.: Macrophage induced T cell mitogen suppression with age. J. Reticuloendoth. Soc., 27: 159–166, 1980.

    CAS  Google Scholar 

  43. Tengerdy, R.P.: The role of vitamin E in immune response and disease resistance in chickens. Avian Dis. J., 34: 848–854, 1990b.

    Article  CAS  Google Scholar 

  44. Carpenter, M.P.: Effects of vitamin E on the immune system, in Vitamins and Cancer, edited by Meysberry, F.L. and Prasad, K.N., Basel, Switzerland, Karger, 1986, pp. 199–211.

    Google Scholar 

  45. Garry, P.J., Goodwin, J.S., Hunt, W.C., Hooper, E.M., and Leonard, A.G.: Nutritional status in a healthy elderly population: dietary and supplemental intakes. Am. J. Clin. Nutr., 36: 319–331, 1982.

    PubMed  CAS  Google Scholar 

  46. Porrini, M., Simonetti, P., Ciappellano, S., and Testolin, G.: Vitamin A, E and C nutriture of elderly people of North Italy. Internat. J. Vit. Nutr. Res., 57: 349–355, 1987.

    CAS  Google Scholar 

  47. Vandewoude, M.F.J., and Vandewoude, M.G.: Vitamin E status in a normal population: the influence of age. J. Am. Coll. Nutr., 6: 307–311, 1987.

    PubMed  CAS  Google Scholar 

  48. Harman, D.: The free-radical theory of aging, in Free Radicals in Biology, edited by Pryor, W.A., New York, Academic Press, 1982, pp. 255–273.

    Google Scholar 

  49. Harman, D.: Free radical theory of aging: beneficial effect of antioxidants on the lifespan of male NZB mice; role of free radical reactions in the deterioration of the immune system with age and in the pathogenesis of systemic lupus erythematosus. Age, 3: 64–73, 1980.

    Article  CAS  Google Scholar 

  50. Meydani, S.N., Cathcart, E.S., Hopkins, R.E., Meydani, M., Hayes, K.C., and Blumberg, J.B.: Antioxidants in experimental amyloidosis of young and old mice, in Fourth International Symposium on Amyloidosis, edited by Glenner, G.G., Asserman, E.P., Benditt, E., Calkins, E., Cohen, A.S., Zucker-Franklin, D., New York, Plenum Press, 1986, pp. 683–692.

    Google Scholar 

  51. Cannon, J.G., Meydani, S.N., Fielding, R.A., Meydani, M., Fiatarone, M.A., Meydani, M., Farhangmehr, M., Orencole, S.F., Blumberg, J.B., and Evans, W.J.: The acute phase response in exercise II. Associations between vitamin E, cytokines and muscle proteolysis. Am. J. Physiol., 260: R1235–R1240, 1991.

    Google Scholar 

  52. Cannon, J.G., Orencole, S.F., Fielding, R.A., Meydani, M., Meydani, S.N., Fiatarone, M.A., Blumberg, J.B., and Evans, W.J.: Acute phase response in exercise: interaction of age and vitamin E on neutrophils and muscle enzyme release. Am. J. Physio. 259: R1214–R1219, 1990.

    Google Scholar 

  53. Ziemlanski, S., Wartanowicz, M., Kios, A., Raczka, A., and Kios, M.: The effects of ascorbic acid and alpha-tocopherol supplementation on serum proteins and immunoglobulin concentrations in the elderly. Nutr. Int., 2: 1–5, 1986.

    Google Scholar 

  54. Harman, D., and Miller, R.W.: Effect of vitamin E on the immune response to influenza virus vaccine and incidence of infectious disease in man. Age, 9: 21–23, 1986.

    Article  Google Scholar 

  55. Furukawa, T., Meydani, S.N., and Blumberg, J.B.: Reversal of age-associated decline in immune responsiveness by dietary glutathione supplementation in mice. Mech. Ageing and Devel., 38: 107–117, 1987.

    Article  CAS  Google Scholar 

  56. Franklin, R.A., Li, Y.M., Arkins, S., and Kelley, K.W.: Glutathione augments in vitro proliferative responses of lymphocytes to Concanavalin A to a greater degree in old than in young rats. J. Nutr., 120: 1710–1717, 1990.

    PubMed  CAS  Google Scholar 

  57. Abdulla, M., Jagerstad, M., Nordern, A., Orist, I., and Svensson, S.: Dietary intake of electrolytes and trace elements in the elderly. Nutr. Metab., 21(Suppl): 41–44, 1977.

    PubMed  CAS  Google Scholar 

  58. Watson, R.R., Prabhala, R.H., Plezia, P.M., and Alberts, D.S.: Effect of β-carotene on lymphocyte subpopulations in elderly humans: evidence for a dose-response relationship. Am. J. Clin. Nutr., 53: 90–94, 1991.

    PubMed  CAS  Google Scholar 

  59. Chavance, M., Brubacher, G., Herbeth, B., Vernhes, G., Mikstacki, T., Dete, F., Fournier, C., and Janot, C.: Immunological and nutritional status among the elderly, in Lymphoid Cell Functions in Aging, edited by De Wick, A.L., Paris, Eurage, 1984, pp. 231–237.

    Google Scholar 

  60. Chavance, M., Brubacher, G., Herberth, B., Vernhes, G., Mistacki, T., Dete, F., Fournier, C., and Janot, C.: Immunological and nutritional status among the elderly, in Nutrition, Immunity, and Illness in the Elderly, edited by Chandra, R.K., New York, Pergamon Press, 1985, pp. 137–142, 1985.

    Google Scholar 

  61. Ritenbaugh, C.: Carotenoids and cancer. Nutr. Today, 1: 14–19, 1987.

    Article  Google Scholar 

  62. Salonen, J.T., Salonen, R., Lappetelainen, R., Maenpaa, P.H., Alfthan, G., and Puska, P.: Risk of cancer in relation to serum concentrations of selenium and vitamin A and E: matched case-control analysis of prospective data. Br. Med. J. [Clin. Res.], 290(6466): 417–420, 1985.

    Article  CAS  Google Scholar 

  63. Stahelin, H.B. Rosel, F., Buess, E., and Brubacher, G.: Cancer, vitamins and plasma lipids: prospective Basel study. J.N.C.I., 73: 1463–1468, 1984.

    CAS  Google Scholar 

  64. Wald, N.J., Boreham, J., Hayward, J.L., and Bulbrook, R.D.: Plasma retinol, beta-carotene and vitamin E levels in relation to the future risk of breast cancer. Br. J. Cancer, 49: 321–324, 1984.

    PubMed  CAS  Google Scholar 

  65. Kok, F.J., Van Duijn, C., Hofman, A., Vermeeren, R., de Bruijn, A.M., and Valkenburg, H.A.: Micronutrients and the risk of lung cancer. N. Engl. J. Med., 316: 1416, 1987.

    PubMed  CAS  Google Scholar 

  66. Lopez-S, A., Le Gardeur, B.Y., and Johnson, W.D.: Vitamins and lung cancer. Am. J. Clin. Nutr., 34: 641, 1987.

    Google Scholar 

  67. Menkes, M.S., Comstock, G.W., Vuillemier, J.P., Helsing, K.J., Rider, A.A., and Brookmezer, R.: Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer. N. Engl. J. Med., 315: 1250–1254, 1986.

    Article  PubMed  CAS  Google Scholar 

  68. Knekt, P., Aromaa, A., Maatela, J., Aaran, R., Nikkari, T., Hakama, M., Hakulinen, T., Peto, R., Saxen, E., and Teppo, L.: Serum vitamin E and risk of cancer among Finnish men during a 10-year follow-up. Am. J. Epidemiol., 127: 28–41, 1988.

    PubMed  CAS  Google Scholar 

  69. Meydani, S.N., Shapiro, A.C., Meydani, M., Macauley, J.B., and Blumberg, J.B.: Effect of age and dietary fat (fish, corn and coconut oils) on tocopherol status of C57BL/6 Nia mice. Lipids, 22: 345–350, 1987.

    PubMed  CAS  Google Scholar 

  70. Meydani, M., Natiello, F., Goldin, B., Free, N., Woods, M., Schaefer, E. Blumberg, J.B., and Gorbach, S.: Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women. J. Nutr., 121: 484–491, 1991.

    PubMed  CAS  Google Scholar 

  71. Meydani, S.N., Lichtenstein, A.H., Cornwall, S., Rasmussen, H., Nerad, J., Dinarello, C.A., and Schaefer, E.J.: Effect of low fat, low cholesterol (LF-LCHL) diet enriched in N-3 fatty acids (FA) on the immune response of humans. FASEB J., 5: A1449, 1991.

Download references

Author information

Authors and Affiliations

  1. USDA — Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA, 02111

    Simin Nikbin Meydani

Authors
  1. Simin Nikbin Meydani
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Meydani, S.N. Dietary modulation of the immune response in the aged. AGE 14, 108–115 (1991). https://doi.org/10.1007/BF02435016

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02435016

Keywords

Search

Navigation