Ascorbic Acid and the Immune Response

  • Brian Leibovitz
  • Benjamin V. Siegel


Since the introduction of ascorbic acid as an antiviral and antibacterial agent (Klenner, 1951; McCormick, 1952; Klenner, 1974) interest has focused on the possible immunologic mechanisms involved in its protective effect. The role of ascorbic acid in the immune response is reviewed here with regard to cellular and humoral functions, and experiments pertaining to the role of ascorbic acid in autoimmunity and anaphylaxis are discussed.


Ascorbic Acid Spleen Weight Dehydroascorbic Acid Total Vitamin Ascorbate Free Radical 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References Cited

  1. Anderson, R. (1979) Effects of ascorbate on leukocytes. II. Effects of ascorbic acid and calcium and sodium ascorbate on neutrophil phagocytosis and post-phagocytic metabolic activity. South African Med. J. 56: 401–404.Google Scholar
  2. Anderson, R., and Theron, A. (1979) Effects of ascorbate on leukocytes. I. Effects of ascorbate on neutrophil motility and intracellular cyclic nucleotide levels in vitro. South African Med. J. 56: 394–400.Google Scholar
  3. Anderson, R., Oosthuizen, R., Maritz, R., Theron, A., and Van Rensburg, A. J. (1980) The effects of increasing weekley doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am. J. Clin. Nutr. 33: 71–76.Google Scholar
  4. Anthony, L. E., Kurahara, C. G., and Taylor, K. B. (1979) Cell-mediated cytotoxicity and humoral immune response in ascorbic acid-deficient guinea pigs. Am. J. Clin. Nutr. 32: 1691–1698.Google Scholar
  5. Atherton, J. G., Kratzing, C. C., and Fisher, A. (1978) The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by Coronavirus. Arch. Virology 56: 195–199.CrossRefGoogle Scholar
  6. Baehner, R. L., Boxer, L. A., Allen, J. M., and Davis, J. (1977) Autooxidation as a basis for altered function by polymorphonuclear leukocytes. Blood 50: 327–335.Google Scholar
  7. Baird, I. M., Hughes, R. E., Wilson, H. K., Davies, J. E. W., and Howard, A. N. (1979) The effect of ascorbic acid and flavonoids on the occurrence of symptoms normally associated with the common cold. Am. J. Clin. Nutr. 32: 1686–1690.Google Scholar
  8. Banic, S. (1975) Prevention of rabies by vitamin C. Nature 258: 153–154.CrossRefGoogle Scholar
  9. Bates, C. J., Levene, C. I., Oldroyd, R. S., and Lachmann, P. J. (1978) Complement component Clq is insensitive to acute vitamin C deficiency in guinea pigs. Biochem. Biophys. Acta 540: 423–430.CrossRefGoogle Scholar
  10. Boxer, L. A., Watanabe, A. M., Rister, M., Besch, H. R., Allen, J., and Baehner, R. L. (1976) Correction of leukocyte function in Chediak-Higashi syndrome by ascorbate. New Engl. J. Med. 295: 1041–1045.CrossRefGoogle Scholar
  11. Chatterjee, I. B., Majumder, A. K., Nandi, B. K,, and Subramanian, N, (1975) Synthesis and some major functions of vitamin C in animals. Ann, N.Y. Acad. Sci. 258: 24–47.CrossRefGoogle Scholar
  12. Chatterjee, G. C., Majumder, P. K., Banerjee, S. K., Roy, R. K., and Rudrapal, D. (1975a) Relationships of protein and mineral intake to L-ascorbic acid metabolism, including considerations of some directly related hormones. Ann. N.Y. Acad. Sci. 258: 382–400.CrossRefGoogle Scholar
  13. Chretien, J. H., and Garagusi, V. F. (1973) Correction of corticosteroid-induced defects of polymorphonuclear neutrophil function by ascorbic acid. J. Reticuloendothelial Soc. 14: 280–286.Google Scholar
  14. Cottingham, E., and Mills, C. A. (1943) Influence of environmental temperature and vitamin deficiency on phagocytic functions. J. Immunol. 47: 493–502.Google Scholar
  15. Csaba, B., and Toth, S. (1971) The effect of temperature and some mediator antagonists on anaphylactic shock in mice. Int. Arch, Allergy 40: 316–320.CrossRefGoogle Scholar
  16. Dawson, W., Starr, M. S., and West, G. B. (1966) Inhibition of anaphylactic shock in the rat by antihistamines and ascorbic acid. Br. J. Pharmac. Chemother. 27: 249–255.Google Scholar
  17. DeChatelet, L. R., Cooper, M. R., and McCall, C. E. (1971) Stimulation of leukocyte hexose monophosphate shunt activity by ascorbic acid, Clin. Res. 19: 44.Google Scholar
  18. DeChatelet, L, R., Cooper, M. R., and McCall, C. E, (1972) Stimulation of the hexose monophosphate shunt in human neutrophils by ascorbic acid: mechanism of action. Antimicrobial Agents and Chemotherapy 1: 12–16.Google Scholar
  19. DeChatelet, L. R., McCall, C. E., Cooper, M. R., and Shirley, P. S. (1974) Ascorbic acid levels in phagocytic cells. Proc. Soc. Exp. Biol. Med. 145: 1170–1173.Google Scholar
  20. Fessenden, R. W., and Verma, N. C. (1978) A time resolved electron spin resonance study of the oxidation of ascorbic acid by hydroxyl radical. Biophys. J. 24: 93–101.CrossRefGoogle Scholar
  21. Gallin, J. I., Elin, R. J., Hubert, R. T., Fauci, A. S., Kaliner, M. A., and Wolff, S. M. (1979) Efficacy of ascorbic acid in Chediak-Higashi syndrome: studies in humans and mice. Blood 53: 226–234.Google Scholar
  22. Ganguly, R., Durieux, M. F., and Waldman, R. H, (1976) Macrophage function in vitamin C-deficient guinea pigs. Am. J. Clin. Nutr. 29: 762–765.Google Scholar
  23. Goetzl, E. J., Wasserman, S. I., Gigli, I., and Austen, K. F. (1974) Enhancement of random migration and chemotactic response of human leukocytes by ascorbic acid. J. Clin. Invest. 53: 813–818.CrossRefGoogle Scholar
  24. Imanaga, Y. (1955) Autooxidation of L-ascorbic acid and imidazole nucleus. I. The effects of imidazole derivatives on the autooxidation of L-ascorbic acid. J. Biochem. 42: 657–667.Google Scholar
  25. Kalden, J. R., and Guthy, E. A. (1972) Prolonged skin allograft survival in vitamin C-deficient guinea pigs. Europ. Surg. Res. 4: 114–119.CrossRefGoogle Scholar
  26. Klenner, F. R. (1951) Massive doses of vitamin C and the virus diseases. J. Southern Med. and Surgery 103: 101–107.Google Scholar
  27. Klenner, F. R. (1974) Significance of high daily intake of ascorbic acid in preventive medicine. J. Int. Academy of Preventive Medicine 1: 45–69.Google Scholar
  28. Kumar, M., and Axelrod, A. E. (1969) Circulating antibody formation in scorbutic guinea pigs. J. Nutr. 98: 41–44.Google Scholar
  29. Leibovitz, B. (1979) Ascorbic acid, lipid peroxidation, and aging. Thesis submitted to the Department of Biology, Portland State University, Portland, Oregon 97201.Google Scholar
  30. Leibovitz, B., and Siegel, B. V. (1980) Aspects of free radical reactions in biological systems: aging. J. Gerontology 35: 45–56.Google Scholar
  31. Long, D. A. (1950) Ascorbic acid and the production of antibody in the guinea pig. Br. J. Exp. Pathology 31: 183–188.Google Scholar
  32. Lowry, O. H., Lopez, J. A., and Bessey, O. A. (1945) The determination of ascorbic acid in small amounts of blood serum. J. Biol. Chem. 160: 609–615.Google Scholar
  33. MacLennan, W. J., and Hamilton, J. C. (1976) The effect of leukocytosis on leukocyte ascorbic acid levels. Age and Aging 5: 43–48.CrossRefGoogle Scholar
  34. Matheisz, J. S., and Allen, J. C. (1979) Fatigue of human polymorphonuclear leukocyte function associated with bacterial ingestion. Clin. Immunology and Immunopathology 12: 125–131.CrossRefGoogle Scholar
  35. McCall, C. E., DeChatelet, L., and Cooper, R. (1971) The effect of ascorbic acid on neutrophil bactericidal activity. Clin. Res. 19: 47.Google Scholar
  36. McCormick, W. J. (1952) Ascorbic acid as a chemotherapeutic agent. Arch. Pediatrics 69: 151–155.Google Scholar
  37. Morton, J. I., and Siegel, B. V. (1980) Stimulation of the reticuloendothelial system and autoimmunity. In Macrophages and Lymphocytes, part B (M. R. Escobar and H. Friedman, eds.), Plenum Press, N. Y., pp.307–315.Google Scholar
  38. Mueller, P. S., Kies, M. W., Alvord, E. C., and Shaw, C. M. (1962) Prevention of experimental allergic encephalomyelitis by vitamin C deprivation. J. Exp. Med. 115: 329–338.CrossRefGoogle Scholar
  39. Mueller, P. S., and Kies, M. W. (1962) Suppression of tuberculin reaction in the scorbutic guinea pig. Nature 195: 813.CrossRefGoogle Scholar
  40. Murata, A., Kitagawa, K., Saruno, R. (1971) Inactiviation of bacteriophages by ascorbic acid. Agr. Biol, Chem. 35: 294–296.CrossRefGoogle Scholar
  41. Murata, A., Kitagawa, K., Inmaru, H., and Saruno, R. (1972) Inactivation of single-stranded DNA and RNA phages by ascorbic acids and thiol reducing agents. Agr. Biol, Chem. 36: 2597–2599.CrossRefGoogle Scholar
  42. Murata, A., Oyadomari, R., Ohashi, T., and Kitagawa, K. (1975) Mechanism of inactivation of bacteriophage delta-A containing single-stranded DNA by ascorbic acid. J. Nutr. Sci. Vitaminol. 21: 261–269.CrossRefGoogle Scholar
  43. Murphy, B. L., Krushak, D. H., Maynard, J. E., and Bradley, D. W. (1974) Ascorbic acid and its effects on parainfluenza type III virus infection in cotton-topped marmosets. Laboratory Animal Science 24: 229–232.Google Scholar
  44. Nishikimi, M. (1975) Oxidation of ascorbic acid with superoxide anion generated by the xanthine-xanthine oxidase system. Biochem. Biophys. Res. Comm. 63: 463–468.CrossRefGoogle Scholar
  45. Nungester, W. J., and Ames, A. M. (1948) The relationship between ascorbic acid and phagocytic activity. J. Infect. Disease 83: 50–54.CrossRefGoogle Scholar
  46. Olsen, G. E., and Polk, H. C. (1977) In vitro effect of ascorbic acid on corticosteroid-caused neutrophil dysfunction. J. Surgical Res. 22: 109–112.CrossRefGoogle Scholar
  47. Oyanagui, Y. (1976) Inhibition of superoxide anion production in macrophages by anti-inflammatory drugs. Biochem. Pharmacol. 25: 1473–1480.CrossRefGoogle Scholar
  48. Pauling, L. (1976) Vitamin C and the common cold. Medical Tribune, March 24: 1–4.Google Scholar
  49. Picatoste, F., Blanco, I., and Palacios, J. M. (1977) The presence of two cellular pools of rat brain histamine, J. Neurochem. 20: 735–737.CrossRefGoogle Scholar
  50. Prinz, W., Bortz, R., Bregin, B., and Hersch, M. (1977) The effect of ascorbic acid supplementation on some parameters of the human immunological defense system. Int. J. Vit. Nutr. Res. 47: 248–257.Google Scholar
  51. Ramirez, I., Richie, E., Wang, Y. M., and Van Eys, J. (1979) The effect of L-ascorbic acid in vitro on lymphocyte reactivity to mitogens. Fed. Proc. 38: 763.Google Scholar
  52. Robinson. A. B., Catchpool, J. F., and Pauling, L. (1975) Decreased white blood cell count in people who supplement their diet with L-ascorbic acid. IRCS Medical Science 3: 259.Google Scholar
  53. Roe, J. H., and Kuether, C. A. (1943) The determination of ascorbic acid in whole blood and urine through the 2,4-dinitrophenylhydrazine derivative of dehydroascorbic acid. J. Biol. Chem. 147: 399–407.Google Scholar
  54. Rosen, H., and Klebanoff, S. J. (1979) Bactericidal activity of a superoxide anion-generating system. J. Exp. Med. 149: 27–39.CrossRefGoogle Scholar
  55. Salin, M. L., and McCord, J. M. (1975) Free radicals and inflammation. Protection of phagocytosing leukocytes by superoxide dismutase. J. Clin. Invest. 56: 1319–1323.CrossRefGoogle Scholar
  56. Schwerdt, P. R., and Schwerdt, C. E. (1975) Effect of ascorbicacid on Rhinovirus replication in WI-38 cells. Proc. Soc, Exp. Biol. Med. 148: 1237–1243.Google Scholar
  57. Shilotri, P. G., and Bhat, K. S. (1977) Effect of mega doses of vitamin C on bactericidal activity of leukocytes. Am. J. Clin. Nutr. 30: 1077–1081.Google Scholar
  58. Siegel, B. V., and Morton, J. I. (1970) Autoimmune disease in New Zealand Black mice infected with Rauscher leukemia virus. J. Natl. Cancer Inst. 45: 189–193.Google Scholar
  59. Siegel, B. V. (1974) Enhanced interferon response to murine leukemia virus by ascorbic acid. Infect. Immunity 10: 409–410.Google Scholar
  60. Siegel, B. V. (1975) Enhancement of interferon production by poly(rI) poly(rC) in mouse cell cultures by ascorbic acid. Nature 254:531:532.Google Scholar
  61. Siegel, B. V., and Morton, J. I. (1977) Vitamin C and the immune response. Experientia 33: 393–395.CrossRefGoogle Scholar
  62. Siegel, B. V., and Leibovitz, B. (1979) Vitamin C in aging and cancer. Int. J. Vit. Nutr. Res. 49 (suppl. 19): 9–24.Google Scholar
  63. Smith, W. B., Shohet, S. B., Zagjeski, E., and Lubin, B. H. (1975) Alteration in human granulocyte function after in vitro incubation with L-ascorbic acid. Ann. N.Y. Acad. Sci. 258: 329–338.CrossRefGoogle Scholar
  64. Stankova, L., Gerhardt, N. B., Nage, L., and Bigley, R. H. (1975) Ascorbate and phagocyte function. Infect. Immunity 12: 252–256.Google Scholar
  65. Tauber, A. I., Gabig, T. G., and Babior, B. M. (1979) Evidence for production of oxidizing radicals by the particulate superoxide-forming system from human neutrophils. Blood 53: 666–676.Google Scholar
  66. Terezhalmy, G. T., Bottomley, W. K., and Pelleu, B. G. (1978) The use of water-soluble bioflavonoid-ascorbic acid complex in the treatment of recurrent herpes labialis. Oral Surgery, Oral Medicine, Oral Pathology 45: 56–61.CrossRefGoogle Scholar
  67. Thurman, G. B., and Goldstein, A. L. (1979) Suppression of immunological responsivity in guinea pigs by ascorbic acid depletion. Fed. Proc. 38: 1173.Google Scholar
  68. Valic, F., and Zuskin, E. (1973) Pharmacological prevention of acute ventilatory capacity reduction in flax dust exposure. Br. J. Industrial Med. 30: 381–384.Google Scholar
  69. Vallance, S. (1977) Relationship between ascorbic acid and serum proteins of the immune system. Br. Med. J. 2: 437–438.CrossRefGoogle Scholar
  70. Weir, D. M. (1974) Handbook of Experimental Immunology, volume 3, Blackwell Scientific Publications, London.Google Scholar
  71. Yonemoto, R. H., Chretien, P. B., and Fehniger, T. F. (1976) Enhanced lymphocyte blastogenesis by oral ascorbic acid. Am. Soc. Clin. Oncology Abstracts 17: 288.Google Scholar
  72. Zannoni, V., Lynch, M., Goldstein, S., and Sato, P. (1974) A rapid micromethod for the determination of ascorbic acid in plasma and tissues. Biochemical Med. 11: 41–48.CrossRefGoogle Scholar
  73. Zuskin, E., Lewis, A. J., and Bouhuys, A. (1973) Inhibition of histamine-induced airway constriction by ascorbic acid. J. Allergy Clin. Immunol. 51: 218–226.CrossRefGoogle Scholar
  74. Zweiman, B., Schoenwetter, W. F., and Hildreth, E. A. (1966) The effect of the scorbutic state of tuberculin hypersensitivity in the guinea pig. I. Passive transfer of tuberculin hypersensitivity. J. Immunol. 96: 296–300.Google Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Brian Leibovitz
    • 1
  • Benjamin V. Siegel
    • 1
  1. 1.Department of PathologyUniversity of Oregon Health Sciences CenterPortlandUSA

Personalised recommendations