Micronutrients at the interface between inflammation and infection - ascorbic acid and calciferol. part 1: General overview with a focus on ascorbic acid

Inflammation and Allergy - Drug Targets

Volumn 10, Issue 1, 2011, Pages 54-63

  Ströhle, Alexander ^a   Wolters, Maike ^a   Hahn, Andreas ^a  

^a LEIBNIZ UNIVERSITY HANNOVER   (Germany)

Author keywords

Immune system; Infections; Micronutrients; Phagocytosis; Vitamin C

Indexed keywords

ALPHA TOCOPHEROL; ASCORBIC ACID; CARNITINE; CYANOCOBALAMIN; ERGOCALCIFEROL; IRON; NITRIC OXIDE; PYRIDOXINE; RETINOL; SELENIUM; TETRAHYDROBIOPTERIN; TRACE ELEMENT; ZINC;

ASCORBIC ACID DEFICIENCY; BIOCHEMISTRY; CELL ACTIVITY; CELL FUNCTION; DNA REPLICATION; EPIGENETICS; HUMAN; IMMUNE SYSTEM; IMMUNOCOMPETENCE; IMMUNOCOMPETENT CELL; INFECTION; INFLAMMATION; LYMPHOCYTE; MONOCYTE; NEUTROPHIL; OXIDATIVE STRESS; PHAGOCYTE; PHAGOCYTOSIS; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE;

EID: 79551636801     PISSN: 18715281     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152811794352105     Document Type: Review

References (193)

1. Wintergerst, E.S.; Maggini, S.; Hornig, D.H. Contribution of selected vitamins and trace elements to immune function. Ann. Nutr. Metab., 2007, 51, 301-323.
2. Field, C.J.; Johnson, I.R.; Schley, P.D. Nutrients and their role in host resistance to infection. J. Leukoc. Biol., 2002, 71, 16-32.
3. Jain, A.L. Influence of vitamins and trace-elements on the incidence of respiratory infection in the elderly. Nutr. Res., 2002, 22, 85-87.
4. El-Kadiki, A.; Sutton, A.J. Role of multivitamins and mineral supplements in preventing infections in elderly people: systematic review and meta-analysis of randomised controlled trials. BMJ., 2005, 330, 871.
5. Meydani, A.; Ahmed, T.; Meydani, S.N. Aging, nutritional status, and infection in the developing world. Nutr. Rev., 2005, 63, 233-246.
6. Meydani, S.N.; Han, S.N.; Wu, D. Vitamin E and immune response in the aged: molecular mechanisms and clinical implications. Immunol. Rev., 2005, 205, 269-284.
7. Bunout, D.; Barrera, G.; Hirsch, S.; Gattas, V.; de la Maza, M.P.; Haschke, F.; Steenhout, P.; Klassen, P.; Hager, C.; Avendaño, M.; Petermann, M.; Muñoz, C. Effects of a nutritional supplement on the immune response and cytokine production in free-living Chilean elderly. JPEN J. Parenter. Enteral. Nutr., 2004, 28, 348-354.
8. Langkamp-Henken, B.; Bender, B.S.; Gardner, E.M.; Herrlinger-Garcia, K.A.; Kelley, M.J.; Murasko, D.M.; Schaller, J.P.; Stechmiller, J.K.; Thomas, D.J.; Wood, S.M. Nutritional formula enhanced immune function and reduced days of symptoms of upper respiratory tract infection in seniors. J. Am. Geriatr. Soc., 2004, 52, 3-12.
9. Langkamp-Henken, B.; Wood, S.M.; Herlinger-Garcia, K.A.; Thomas, D.J.; Stechmiller, J.K.; Bender, B.S.; Gardner, E.M.; DeMichele, S.J.; Schaller, J.P.; Murasko, D.M. Nutritional formula improved immune profiles of seniors living in nursing homes. J. Am. Geriatr. Soc., 2006, 54, 1861-1870.
10. van Lettow, M.; Fawzi, W.W.; Semba, R.D. Triple trouble: the role of malnutrition in tuberculosis and human immunodeficiency virus co-infection. Nutr. Rev., 2003, 61, 81-90.
11. Semba, R.D.; Tang, A.M. Micronutrients and the pathogenesis of human immunodeficiency virus infection. Br. J. Nutr., 1999, 81, 181-189.
12. Colecraft, E. HIV/AIDS: nutritional implications and impact on human development. Proc. Nutr. Soc., 2008, 67, 109-113.
13. Adam, O. Dietary therapy for inflammatory rheumatic diseases. Dtsch. Med. Wochenschr., 2009, 134, 1759-1763.
14. Adam, O.; Fasse, S.; Ditrich, O. Diet in rheumatic disease. Z. Rheumatol., 2009, 68, 549-558.
15. Hahn, A.; Ströhle, A.; Wolters, M. Nutrition in rheumatic-type diseases. Med. Monatsschr. Pharm., 2007, 30, 138-46.
16. Meydani, S.N.; Wu, D. Nutrition and age-associated inflammation: implications for disease prevention. JPEN J. Parenter. Enteral. Nutr., 2008, 32, 626-629.
17. Biesalski, H.K. Polyphenols and inflammation: basic interactions. Curr. Opin. Clin. Nutr. Metab. Care, 2007, 10, 724-728.
18. Lau, F.C.; Shukitt-Hale, B.; Joseph, J.A. Nutritional intervention in brain aging: reducing the effects of inflammation and oxidative stress. Subcell. Biochem., 2007, 42, 299-318.
19. Calder, P.C.; Albers, R.; Antoine, J.M.; Blum, S.; Bourdet-Sicard, R.; Ferns, G.A.; Folkerts, G.; Friedmann, P.S.; Frost, G.S.; Guarner, F.; Løvik, M.; Macfarlane, S.; Meyer, P.D.; M'Rabet, L.; Serafini, M.; van Eden, W.; van Loo, J.; Vas Dias, W.; Vidry, S.; Winklhofer-Roob, B.M.; Zhao, J. Inflammatory disease processes and interactions with nutrition. Br. J. Nutr., 2009, 101(Suppl 1), S1-45.
20. Pattison, D.J.; Winyard, P.G. Dietary antioxidants in inflammatory arthritis: do they have any role in etiology or therapy? Nat. Clin. Pract. Rheumatol., 2008, 4, 590-596.
21. Bhaskaram, P. Immunobiology of mild micronutrient deficiencies. Br. J. Nutr., 2001, 85(Suppl 2), S75-80.
22. Bhaskaram, P. Micronutrient malnutrition, infection, and immunity: an overview. Nutr. Rev., 2002, 60, S40-45.
23. Ströhle, A.; Hahn, A. Bedeutung von Mikronährstoffen für die Immunkompetenz. MMW-Fortschr. Med., 2009, 151, S. 133-141.
24. Vercelli, D. Genetics, epigenetics, and the environment: switching, buffering, releasing. J. Allergy. Clin. Immunol., 2004, 113, 381-6.
25. Oommen, A.M.; Griffin, J.B.; Sarath, G.; Zempleni, J. Roles for nutrients in epigenetic events. J. Nutr. Biochem., 2005, 16, 74-77.
26. Erickson, K.L.; Medina, E.A.; Hubbard, N.E. Micronutrients and innate immunity. J. Infect. Dis., 2000, 182(Suppl 1), S5-10.
27. Arthur, J.R.; McKenzie, R.C.; Beckett, G.J. Selenium in the immune system. J. Nutr., 2003, 133(Suppl 1), 1457S-1459S.
28. Ibs, K.H.; Rink, L. Zinc-altered immune function. J. Nutr., 2003, 133(Suppl 1), 1452S-1456S.
29. th ed., Williams&Wilkins, Baltimore/Philadelphia/ London, 1994.
30. Pauling, L. Vitamin C and the Common Cold. Freeman, San Francisco, 1970.
31. Hemilä, H.; Douglas, R.M. Vitamin C and acute respiratory infections. Int. J. Tuberc. Lung. Dis., 1999, 3, 756-761.
32. Hemilä, H.; Herman, Z.S. Vitamin C and the common cold: a retrospective analysis of Chalmers' review. J. Am. Coll. Nutr., 1995, 14, 116-123.
33. Hemilä, H. Does vitamin C alleviate the symptoms of the common cold?-a review of current evidence. Scand. J. Infect. Dis., 1994, 26, 1-6.
34. Hemilä, H. Vitamin C and common cold incidence: a review of studies with subjects under heavy physical stress. Int. J. Sports Med., 1996, 17, 379-383.
35. Hemilä, H. Vitamin C and Infectious Diseases. In: Packer, L.; Fuchs, J.; Eds.; Vitamin C in Health and Disease. Marcel Dekker, New York, 1997, pp. 471-503.
36. Hemilä, H. Vitamin C intake and susceptibility to the common cold. Br. J. Nutr., 1997, 77, 59-72.
37. Hemilä, H. Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit. Med. Hypotheses, 1999, 52, 171-178.
38. Hemilä, H. Vitamin C supplementation and common cold symptoms: problems with inaccurate reviews. Nutrition, 1996, 12, 804-509.
39. Douglas, R.M.; Chalker, E.B.; Treacy, B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst. Rev., 2000, (2): CD000980.
40. Douglas, R.M.; Hemilä, H.; D'Souza, R.; Chalker, E.B.; Treacy, B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst. Rev., 2004, (4), CD000980.
41. Douglas, R.M.; Hemilä, H.; Chalker, E.; Treacy, B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev., 2007, (3), CD000980.
42. Douglas, R.M.; Hemilä, H. Vitamin C for preventing and treating the common cold. PLoS Med., 2005, 2, e168.
43. Padayatty, S.J.; Levine, M. New insights into the physiology and pharmacology of vitamin C. CMAJ, 2001, 164, 353-355.
44. Heller, R. Ascorbat. In: Dunkelberg, H.; Gebel, T.; Hartwig, A. (Hrsg.): Handbuch der Lebensmitteltoxikologie. Belastungen, Wirkungen, Lebensmittelsicherheit, Hygiene. Weinheim: Wiley-VCH, 2007, 2135-2162.
45. Padh, H. Cellular functions of ascorbic acid. Biochem. Cell Biol., 1990, 68, 1166-1173.
46. Kaelin, W.G. Proline hydroxylation and gene expression. Annu. Rev. Biochem., 2005, 74, 115-128.
47. Hausinnger, R.P. Fell/alpha-ketoglutarate-dependent hydroxylases and related enzymes. Crit. Rev. Biochem. Mol. Biol., 2004, 39, 21-68.
48. Siddiq, A.; Aminova, L.R.; Ratan, R.R. Prolyl 4-hydroxylase activity-responsive transription factors: from hydroxylation to gene expression and neuroprotection. Front. Biosci., 2008, 13, 2875-2887.
49. Oberritter, H.; Glatthaar, B.; Moser, U.; Schmidt, K.H. Effect of functional stimulation on ascorbate content in phagocytes under physiological and pathological conditions. Int. Arch. Allergy Appl. Immunol., 1986, 81, 46-50.
50. Levine, M.; Conry-Cantilena, C.; Wang, Y.; Welch, R.W.; Washko, P.W.; Dhariwal, K.R.; Park, J.B.; Lazarev, A.; Graumlich, J.F.; King, J.; Cantilena, L.R. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. USA, 1996, 93, 3704-3709.
51. Levine, M.; Wang, Y.; Padayatty, S.J.; Morrow, J. A new recommended dietary allowance of vitamin C for healthy young women. Proc. Natl. Acad. Sci. USA, 2001, 98, 9842-9846.
52. Moser, U. Uptake of ascorbic acid by leukocytes. Ann. N.Y. Acad. Sci., 1987, 498, 200-215.
53. Washko, P.; Rotrosen, D.; Levine, M. Ascorbic acid accumulation in plated human neutrophils. FEBS Lett., 1990, 260, 101-104.
54. Washko, P.; Rotrosen, D.; Levine, M. Ascorbic acid in human neutrophils. Am. J. Clin. Nutr., 1991, 54, 1221-1227.
55. Evans, R.M.; Currie, L.; Campbell, A. The distribution of ascorbic acid between various cellular components of blood, in normal individuals, and its relation to the plasma concentration. Br. J. Nutr., 1982, 47, 473-482.
56. Blanchard, J.; Conrad, K.A.; Watson, R.R.; Garry, P.J.; Crawley, J.D. Comparison of plasma, mononuclear and polymorphonuclear leucocyte vitamin C levels in young and elderly women during depletion and supplementation. Eur. J. Clin. Nutr., 1989, 43, 97-106.
57. Jacob, R.A. Assessment of human vitamin C status. J. Nutr., 1990, 120, 1480-1485.
58. Omaye, S.T.; Schaus, E.E.; Kutnink, M.A.; Hawkes, W.C. Measurement of vitamin C in blood components by highperformance liquid chromatography. Implication in assessing vitamin C status. Ann. N.Y. Acad. Sci., 1987, 498, 389-401.
59. Ströhle, A.; Hahn, A. Vitamin C und Immunfunktion. Med. Monatsschr. Pharm., 2009, 32, 49-54.
60. Mueller, P.S.; Kies, M.W. Suppression of tuberculin reaction in the scorbutic guinea pig. Nature, 1962, 195, 813-814.
61. Kalden, J.R.; Guthy, E.A. Prolonged skin allograft survival in vitamin C-deficient guinea-pigs. Preliminary communication. Eur. Surg. Res., 1972, 4, 114-119.
62. Anthony, L.E.; Kurahara C.G.; Taylor, K.B. Cell-mediated cytotoxicity and humoral immune response in ascorbic aciddeficient guinea pigs. Am. J. Clin. Nutr., 1979, 32, 1691-1699.
63. Goldschmidt, M.C.; Masin, W.J.; Brown, L.R.; Wyde, P.R. The effect of ascorbic acid deficiency on leukocyte phagocytosis and killing of actinomyces viscosus. Int. J. Vitam. Nutr. Res., 1988, 58, 326-334.
64. Shilotri, P.G. Phagocytosis and leukocyte enzymes in ascorbic acid deficient guinea pigs. J. Nutr., 1977, 107, 1513-1516.
65. Shilotri, P.G. Glycolytic, hexose monophosphate shunt and bactericidal activities of leukocytes in ascorbic acid deficient guinea pigs. J. Nutr., 1977, 107, 1507-1512.
66. Alvares, O.; Altman, L.C.; Springmeyer, S.; Ensign, W.; Jacobson, K. The effect of subclinical ascorbate deficiency on periodontal health in nonhuman primates. J. Periodontal Res., 1981, 16, 628-636.
67. Kumar, M.; Axelrod, A.E. Circulating antibody formation in scorbutic guinea pigs. J. Nutr., 1969, 98, 41-44.
68. Anderson, R.; Oosthuizen, R.; Maritz, R.; Theron, A.; Van Rensburg, A.J. The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am. J. Clin. Nutr., 1980; 33, 71-76.
69. Siegel, B.V.; Morton, J.I. Vitamin C and the immune response. Experientia, 1977, 33, 393-395.
70. Corbel, M.J.; Wood, W.A. The effects of ascorbic acid depletion on the immune response of the guinea pig to Brucella abortus strain 19 vaccine. J. Biol. Stand., 1975, 3, 167-170.
71. Murphy, B.L.; Krushak, D.H.; Maynard, J.E.; Bradley, D.W. Ascorbic acid (vitamin C) and its effects on parainfluenza type 3 virus infection in cotton-topped marmosets. Lab. Anim. Sci., 1974, 24, 229-232.
72. Jacob, R.A.; Kelley, D.S.; Pianalto, F.S.; Swendseid, M.E.; Henning, S.M.; Zhang, J.Z.; Ames, B.N.; Fraga, C.G.; Peters, J.H. Immunocompetence and oxidant defense during ascorbate depletion of healthy men. Am. J. Clin. Nutr., 1991, 54, 1302-1309.
73. Harris, L.J.; Passmore, R.; Oxon, B.M.; Pagel, W.; Berlin, M.D. Vitamin C and infection. Lancet, 1937, 2, 183-186.
74. Hume, R.; Weyers, E. Changes in leucocyte ascorbic acid during the common cold. Scott. Med. J., 1973, 18, 3-7.
75. Wilson, C.W. Ascorbic acid function and metabolism during colds. Ann. N.Y. Acad. Sci., 1975, 258, 529-539.
76. Schwartz, A.R.; Togo, Y.; Hornick, R.B.; Tominaga, S.; Gleckman, R.A. Evaluation of the efficacy of ascorbic acid in prophylaxis of induced rhinovirus 44 infection in man. J. Infect. Dis., 1973, 128, 500-505.
77. Winterbourn, C.C.; Vissers, M.C. Changes in ascorbate levels on stimulation of human neutrophils. Biochim. Biophys. Acta, 1983, 763, 175-179.
78. Stankova, L.; Gerhardt, N.B.; Nagel, L.; Bigley, R.H. Ascorbate and phagocyte function. Infect. Immun., 1975, 12, 252-256.
79. Chakrabarti, B.; Banerjee, S. Dehydroascorbic acid level in blood of patients suffering from various infectious diseases. Proc. Soc. Exp. Biol. Med., 1955, 88, 581-583.
80. Webb, A.L.; Villamor, E. Update: effects of antioxidant and nonantioxidant vitamin supplementation on immune function. Nutr. Rev., 2007, 65, 181-217.
81. Ganguly, R.; Waldman, R.H. Macrophage functions in aging: effects of vitamin C deficiency. Allerg. Immunol., 1985, 31, 37-43.
82. Ganguly, R.; Durieux, M.F.; Waldman, R.H. Macrophage function in vitamin C-deficient guinea pigs. Am. J. Clin. Nutr., 1976, 29, 762-765.
83. Goetzl, E.J.; Wasserman, S.I.; Gigli, I.; Austen, K.F. Enhancement of random migration and chemotactic response of human leukocytes by ascorbic acid. J. Clin. Invest., 1974, 53, 813-818.
84. Sandler, J.A.; Gallin, J.I.; Vaughan, M. Effects of serotonin, carbamylcholine, and ascorbic acid on leukocyte cyclic GMP and chemotaxis. J. Cell Biol., 1975, 67, 480-484.
85. Anderson, R.; Theron, A. Effects of ascorbate on leukocytes. I. S. Afr. Med. J., 1979, 56, 394-400.
86. Boxer, L.A.; Vanderbilt, B.; Bonsib, S.; Jersild, R.; Yang, H.H.; Baehner, R.L. Enhancement of chemotactic response and microtubule assembly in human leukocytes by ascorbic acid. J. Cell. Physiol., 1979, 100, 119-126.
87. Gatner, E.M.S.; Anderson, R. An in vitro assessment of cellular and humoral immune function in pulmonary tuberculosis. Clin. Exp. Immunol., 1980, 40, 327-336.
88. Patrone, F.; Dallegri, F.; Lanzi, G.; Sacchetti, C. Prevention of neutrophil chemotactic deactivation by ascorbic acid. Br. J. Exp. Pathol., 1980, 61, 486-489.
89. Anderson, R.; Jones, P.T. Increased leucoattractant binding and reversible inhibition of neutrophil motility mediated by the peroxidase/H2O2/halide system. Clin. Exp. Immunol., 1982, 47, 487-496.
90. Pryzwansky, K.B.; Schliwa, M.; Boxer, L.A. Microtubule organization of unstimulated and stimulated adherent human neutrophils in Chediak-Higashi syndrome. Blood, 1985, 66, 1398-1403.
91. Johnston, C.S.; Huang, S. Effect of ascorbic acid nutriture on blood histamine and neutrophil chemotaxis in guinea pigs. J. Nutr., 1991, 121, 126-130.
92. Johnston, C.S.; Martin, L.J.; Cai, X. Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis. J. Am. Coll. Nutr., 1992, 11, 172-176.
93. Johnston, C.S. The antihistamine action of ascorbic acid. Subcell. Biochem., 1996, 25, 189-213.
94. Schwager, J.; Schulze, J. Modulation of interleukin production by ascorbic acid. Vet. Immunol. Immunopathol., 1998, 64, 45-57.
95. Kennes, B.; Dumont, I.; Brohee, D.; Hubert, C.; Neve, P. Effect of vitamin C supplements on cell-mediated immunity in old people. Gerentology, 1983, 29, 305-310.
96. Nieman, D.C.; Henson, D.A.; McAnulty, S.R.; McAnulty, L.; Swick, N.S.; Utter, A.C.; Vinci, D.M.; Opiela, S.J.; Morrow, J.D. Influence of vitamin C supplementation on oxidative and immune changes after an ultramarathon. J. Appl. Physiol., 2002, 92, 1970-1977.
97. Panush, R.S.; Delafuente, J.C.; Katz, P.; Johnson, J. Modulation of certain immunologic responses by vitamin C. Int. J. Vitam. Nutr. Res., 1979, 19, 179-199.
98. Anderson, R.; Smit, M.J.; Joone, G.K.; Van Staden, A.M. Vitamin C and cellular immune functions. Protection against hypochlorous acid-mediated inactivation of glyceraldehyde-3-phosphate dehydrogenase and ATP generation in human leukocytes as a possible mechanism of ascorbate-mediated immunostimulation. Ann. N.Y. Acad. Sci., 1990, 587, 34-48.
99. Panush, R.S.; Delafuente, J.C.; Katz, P.; Johnson, J. Modulation of certain immunologic responses by vitamin C. III. Potentiation of in vitro and in vivo lymphocyte responses. Int. J. Vitam. Nutr. Res. Suppl., 1982, 23, 35-47.
100. Anderson, R. Ascorbate-mediated stimulation of neutrophil motility and lymphocyte transformation by inhibition of the peroxidase/H2O2/halide system in vitro and in vivo. Am. J. Clin. Nutr., 1981, 34, 1906-1911.
101. Ramirez, I.; Richie, E.; Wang, Y.M.; van Eys, J. Effect of ascorbic acid in vitro on lymphocyte reactivity to mitogens. J. Nutr., 1980, 110, 2207-2215.
102. Levy, R.; Shriker, O.; Porath, A.; Riesenberg, K.; Schlaeffer, F. Vitamin C for the treatment of recurrent furunculosis in patients with impaired neutrophil functions. J. Infect. Dis., 1996, 173, 1502-1505.
103. Boxer, L.A.; Albertini, D.F.; Baehner, R.L.; Oliver, J.M. Impaired microtubule assembly and polymorphonuclear leucocyte function in the Chediak-Higashi syndrome correctable by ascorbic acid. Br. J. Haematol., 1979, 43, 207-213.
104. Boxer, L.A.; Watanabe, A.M.; Rister, M.; Besch, H.R.Jr.; Allen, J., Baehner, R.L. Correction of leukocyte function in Chediak-Higashi syndrome by ascorbate. N. Engl. J. Med., 1976, 295, 1041-1045.
105. Foster, C.S.; Goetzl, E.J. Ascorbate therapy in impaired neutrophil and monocyte chemotaxis. Arch. Ophthalmol., 1978, 96, 2069-2072.
106. Weening, R.S.; Schoorel, E.P.; Roos, D.; van Schaik, M.L.; Voetman, A.A.; Bot, A.A.; Batenburg-Plenter, A.M.; Willems, C.; Zeijlemaker, W.P.; Astaldi, A. Effect of ascorbate on abnormal neutrophil, platelet, and lymphocyte function in a patient with the Chediak-Higashi syndrome. Blood, 1981, 57, 856-865.
107. Saitoh, H.; Komiyama, A.; Norose, N.; Morosawa, H.; Akabane, T. Development of the accelerated phase during ascorbic acid therapy in Chediak-Higashi syndrome and efficacy of colchicine on its management. Br. J. Haematol., 1981, 48, 79-84.
108. Corberand, J.; Nguyen, F.; Fraysse, B.; Enjalbert, L. Malignant external otitis and polymorphonuclear leukocyte migration impairment: improvement with ascorbic acid. Arch. Otolaryngol., 1982, 108, 122-124.
109. Thorner, R.E.; Barker, C.F.; MacGregor, R.R. Improvement of granulocyte adherence and in vivo granulocyte delivery by ascorbic acid in renal transplant patients. Transplantation, 1983, 35, 432-436.
110. Delafuente, J.C.; Panush, R.S. Modulation of certain immunological responses by vitamin C. II. Int. J. Vitam. Nutr. Res., 1980, 50, 44-51.
111. Manzella, J.P.; Roberts, N.J. Human macrophage and lymphocyte responses to mitogen stimulation after exposure to influenza virus, ascorbic acid, and hyperthermia. J. Immunol., 1979, 123, 1940-1944.
112. Joffe, M.I.; Sukha, N.R.; Rabson, A.R. Lymphocyte subsets in measles: depressed helper/inducer subpopulation reversed by in vitro treatment with levamisole and ascorbic acid. J. Clin. Invest., 1983, 72, 971-980.
113. Delafuente, J.C.; Prendergast, J.M.; Modish, A. Immunologic modulation by vitamin C in the elderly. Int. J. Immunopharmacol., 1986, 8, 205-211.
114. Oh, C.; Nakano, K. Reversal by ascorbic acid of suppression by endogenous histamine of rat lymphocyte blastogenesis. J. Nutr., 1988, 118, 639-44.
115. Smit, M.J.; Anderson, R. Inhibition of mitogen-activated proliferation of human lymphocytes by hypochlorous acid in vitro. Agents Actions, 1990, 30, 338-343.
116. Standefer, J.C.; Vanderjagt, D.; Anderson, R.E.; Garry, P.J.; Pogue, L. Protective effect of ascorbate on radiationsensitive thymidine uptake by lymphocytes. Ann. N.Y. Acad. Sci., 1987, 498, 519-521.
117. Fraser, R.C.; Pavlovic, S.; Kurahara, C.G., Murata, A.; Peterson, N.S.; Taylor, K.B.; Feigen, G.A. The effect of variations in vitamin C intake on the cellular immune response of guinea pigs. Am. J. Clin. Nutr., 1980, 33, 839-847.
118. Kristensen, B.; Thomsen, P.D.; Palludan, B.; Wegger, I. Mitogen stimulation of lymphocytes in pigs with hereditary vitamin C deficiency. Acta. Vet. Scand., 1986, 27, 486-496.
119. Anderson, R. Assessment of oral ascorbate in three children with chronic granulmatous disease and defective neutrophil motility over a 2-year period. Clin. Exp. Immunol., 1981, 43, 180-188.
120. Yonemoto, R.H. Vitamin C and immune responses in normal controls and cancer patients. Int. J. Vitam. Nutr. Res., 1979, 19, 143-154.
121. O'Brien, B.C.; McMurray, D.N. Human plasma lipid and immunologic responses to eggs and ascorbic acid. Nutr. Res., 1988, 8, 353-366.
122. Penn, N.D.; Purkins, L.; Kelleher, J.; Heatley, R.V.; Mascie-Taylor, B.H.; Belfield, P.W. The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients. Age Ageing, 1991, 20, 169-174.
123. Gallin, J.I.; Elin, R.J.; Hubert, R.T.; Fauci, A.S.; Kaliner, M.A.; Wolff, S.M. Efficacy of ascorbic acid in Chediak-Higashi syndrome (CHS): studies in humans and mice. Blood, 1979, 53, 226-234.
124. Kay, N.E.; Holloway, D.E.; Hutton, S.W.; Bone, N.D.; Duane, W.C. Human T-cell function in experimental ascorbic acid deficiency and spontaneous scurvy. Am. J. Clin. Nutr., 1982, 36, 127-130.
125. Goodwin, J.S.; Garry, P.J. Relationship between megadose vitamin supplementation and immunological function in a healthy elderly population. Clin. Exp. Immunol., 1983, 51, 647-653.
126. Li, Y.; Lovell, R.T. Elevated levels of dietary ascorbic acid increase immune response in channel catfish J. Nutr., 1985, 115, 123-131.
127. Wahli, T.; Meier, W.; Pfister, K. Ascorbic acid induced immunemediated decrease in mortality in Ichthyophthirius mulfiliis infected rainbow-trout. Acta Trop., 1986, 43, 287-289.
128. Waagbø, R.; Sandnes, K.; Glette, J.; Nilsen, E.R.; Albrektsen, S. Dietary vitamin B6 and C. Ann. N.Y. Acad. Sci., 1992, 669, 379-382.
129. White, L.A.; Freeman, C.Y.; Forrester, B.D.; Chappell, W.A. In vitro effect of ascorbic acid on infectivity of herpesviruses and paramyxoviruses. J. Clin. Microbiol., 1986, 24, 527-531.
130. Cathcart, R.F.3rd. Vitamin C in the treatment of acquired immune deficiency syndrome (AIDS). Med. Hypotheses., 1984, 14, 423-433.
131. Terezhalmy, G.T.; Bottomley, W.K.; Pelleu, G.B. The use of water-soluble bioflavonoid-ascorbic acid complex in the treatment of recurrent herpes labialis. Oral Surg. Oral Med. Oral Pathol., 1978, 45, 56-62.
132. Hovi, T.; Hirvimies, A.; Stenvik, M.; Vuola, E.; Pippuri, R. Topical treatment of recurrent mucocutaneous herpes with ascorbic acidcontaining solution. Antiviral Res., 1995, 27, 263-270.
133. Schwerdt, P.R.; Schwerdt, C.E. Effect of ascorbic acid on rhinovirus replication in WI-38 cells. Proc. Soc. Exp. Biol. Med., 1975, 148, 1237-1243.
134. Harakeh, S.; Jariwalla, R.J.; Pauling, L. Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells. Proc. Natl. Acad. Sci. USA, 1990, 87, 7245-7249.
135. Harakeh, S.; Niedzwiecki, A.; Jariwalla, R.J. Mechanistic aspects of ascorbate inhibition of human immunodeficiency virus. Chem. Biol. Interact., 1994, 91, 207-215.
136. Harakeh, S.; Jariwalla, R.J. Comparative study of the anti-HIV activities of ascorbate and thiol-containing reducing agents in chronically HIV-infected cells. Am. J. Clin. Nutr., 1991, 54, 1231-1235.
137. Harakeh, S.; Jariwalla, R.J. Ascorbate effect on cytokine stimulation of HIV production. Nutrition, 1995, 11, 684-687.
138. Nath, J.; Gallin, J.I. Effect of vitamin C on tubulin tyrosinolation in polymorphonuclear leukocytes. Ann. N.Y. Acad. Sci., 1987, 498, 216-228.
139. Peters-Futre, E.M. Vitamin C, neutrophil function, and upper respiratory tract infection risk in distance runners: the missing link. Exerc. Immunol. Rev., 1997, 3, 32-52.
140. Wintergerst, E.S.; Maggini, S.; Hornig, D.H. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann. Nutr. Metab., 2006, 50, 85-94.
141. Rebouche, C.J. Ascorbic acid and carnitine biosynthesis. Am. J. Clin. Nutr., 1991, 54, 1147-1152.
142. Huang A, Vita JA, Venema RC, Keaney JF Jr. Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. J. Biol. Chem., 2000, 275, 17399-17406.
143. Hallberg, L.; Hulthén, L. Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am. J. Clin. Nutr., 2000, 71, 1147-1160.
144. Dagher, M.C.; Pick, E. Opening the black box: lessons from cellfree systems on the phagocyte NADPH-oxidase. Biochimie, 2007, 89, 1123-1132.
145. Mizrahi, A.; Berdichevsky, Y.; Ugolev, Y.; Molshanski-Mor, S.; Nakash, Y.; Dahan, I.; Alloul, N.; Gorzalczany, Y.; Sarfstein, R.; Hirshberg, M.; Pick, E. Assembly of the phagocyte NADPH oxidase complex: chimeric constructs derived from the cytosolic components as tools for exploring structure-function relationships. J. Leukoc. Biol., 2006, 79, 881-895.
146. Murphy, R.; DeCoursey, T.E. Charge compensation during the phagocyte respiratory burst. Biochim. Biophys. Acta., 2006, 1757, 996-1011.
147. Sumimoto, H.; Miyano, K.; Takeya, R. Molecular composition and regulation of the Nox family NAD(P)H oxidases. Biochem. Biophys. Res. Commun., 2005, 338, 677-686.
148. El-Benna, J.; Dang, P.M.; Gougerot-Pocidalo, M.A.; Elbim, C. Phagocyte NADPH oxidase: a multicomponent enzyme essential for host defenses. Arch. Immunol. Ther. Exp. (Warsz.), 2005, 53, 199-206.
149. Nauseef, W.M. How human neutrophils kill and degrade microbes: an integrated view. Immunol. Rev., 2007, 219, 88-102.
150. Park, J.B. Phagocytosis induces superoxide formation and apoptosis in macrophages. Exp. Mol. Med., 2003, 35, 325-335.
151. Roos, D.; van Bruggen, R.; Meischl, C. Oxidative killing of microbes by neutrophils. Microbes. Infect., 2003, 5, 1307-1315.
152. Segal, A.W. How neutrophils kill microbes. Annu. Rev. Immunol., 2005, 23, 197-223.
153. Halliwell, B. Phagocyte-derived reactive species: salvation or suicide? Trends Biochem. Sci., 2006, 31, 509-515.
154. Splettstoesser, W.D.; Schuff-Werner, P. Oxidative stress in phagocytes-"the enemy within". Microsc. Res. Tech., 2002, 57, 441-455.
155. Anderson, R.; Lukey, P.T. A biological role for ascorbate in the selective neutralization of extracellular phagocyte-derived oxidants. Ann. N.Y. Acad. Sci., 1987, 498, 229-247.
156. McGee, M.P.; Myrvik, Q.N. Phagocytosis-induced injury of normal and activated alveolar macrophages. Infect. Immun., 1979, 26, 910-915.
157. Frei, B. Ascorbic acid protects lipids in human plasma and lowdensity lipoprotein against oxidative damage. Am. J. Clin. Nutr., 1991, 54, 1113-1118.
158. Frei, B.; England, L.; Ames, B.N. Ascorbate is an outstanding antioxidant in human blood plasma. Proc. Natl. Acad. Sci. USA, 1989, 86, 6377-6381.
159. Buettner, G.R. The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch. Biochem. Biophys., 1993, 300, 535-543.
160. Halliwell, B. Free radicals, proteins and DNA: oxidative damage versus redox regulation. Biochem. Soc. Trans., 1996, 24, 1023-1027.
161. Bartlett, D.; Church, D.F.; Bounds, P.L; Koppenol, W.H. The kinetics of the oxidation of L-ascorbic acid by peroxynitrite. Free Radic. Biol. Med., 1995, 18, 85-92.
162. Buettner, G.R.; Jurkiewicz, B.A. Catalytic metals, ascorbate and free radicals: combinations to avoid. Radiat. Res., 1996, 145, 532-541.
163. Chou, P.T.; Khan, A.U. L-ascorbic acid quenching of singlet delta molecular oxygen in aqueous media: generalized antioxidant property of vitamin C. Biochem. Biophys. Res. Commun., 1983, 115, 932-937.
164. Carr, A.C.; Frei, B. Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J., 1999, 13, 1007-1024.
165. Carr, A.C.; Frei, B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am. J. Clin. Nutr., 1999, 69, 1086-107.
166. Rebouche, C.J.; Paulson, D.J. Carnitine metabolism and function in humans. Annu. Rev. Nutr., 1986, 6, 41-66.
167. Famularo, G.; De Simone, C.; Trinchieri, V.; Mosca, L. Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation. Ann. N.Y. Acad. Sci., 2004, 1033, 132-138.
168. Izgüt-Uysal, V.N.; Aβaç, A.; Derin, N. Effect of L-carnitine on carrageenan-induced inflammation in aged rats. Gerontology, 2003, 49, 287-92.
169. Izgüt-Uysal, V.N.; Aβaç, A.; Karadoβan, I.; Derin, N. Effects of Lcarnitine on neutrophil functions in aged rats. Mech. Ageing. Dev., 2003, 124, 341-347.
170. Izgüt-Uysal, V.N.; Agaç, A.; Karadogan, I.; Derin, N. Peritoneal macrophages function modulation by L-carnitine in aging rats. Aging Clin. Exp. Res., 2004, 16, 337-341.
171. Mast, J.; Buyse, J.; Goddeeris, B.M. Dietary L-carnitine supplementation increases antigen-specific immunoglobulin G production in broiler chickens. Br. J. Nutr., 2000, 83, 161-166.
172. Buyse, J.; Swennen, Q.; Niewold, T.A.; Klasing, K.C.; Janssens, G.P.; Baumgartner, M.; Goddeeris, B.M. Dietary L-carnitine supplementation enhances the lipopolysaccharide-induced acute phase protein response in broiler chickens. Vet. Immunol. Immunopathol., 2007, 118, 154-159.
173. Gorren, A.C.; Mayer, B. Tetrahydrobiopterin in nitric oxide synthesis: a novel biological role for pteridines. Curr. Drug. Metab., 2002, 3, 133-157.
174. Wu, G.; Meininger, C.J. Regulation of nitric oxide synthesis by dietary factors. Annu. Rev. Nutr., 2002, 22, 61-86.
175. Patel, K.B.; Stratford, M.R.; Wardman. P.; Everett, S.A. Oxidation of tetrahydrobiopterin by biological radicals and scavenging of the trihydrobiopterin radical by ascorbate. Free Radic. Biol. Med., 2002, 32, 203-211.
176. Huang, A.; Vita, J.A.; Venema, R.C.; Keaney, J.F. Ascorbic acid enhances endothelial nitric oxide synthase activity by increasing intracellular tetrahydrobiopterin. J. Biol. Chem., 2000, 275, 17399-17406.
177. Heller, R.; Unbehaun, A.; Schellenberg, B.; Mayer, B.; Werner-Felmayer, G.; Werner, E.R. L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin. J. Biol. Chem., 2001, 276, 40-47.
178. Schmidt, T.S.; Alp, N.J. Mechanisms for the role of tetrahydrobiopterin in endothelial function and vascular disease. Clin. Sci. (Lond), 2007, 113, 47-63.
179. Nakai, K.; Urushihara, M.; Kubota, Y.; Kosaka, H. Ascorbate enhances iNOS activity by increasing tetrahydrobiopterin in RAW 264.7 cells. Free Radic. Biol. Med., 2003, 35, 929-937.
180. Kuzkaya, N.; Weissmann, N.; Harrison, D.G.; Dikalov, S. Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase. J. Biol. Chem., 2003, 278, 22546-22554.
181. d'Uscio, L.V.; Milstien, S.; Richardson, D.; Smith, L.; Katusic, Z.S. Long-term vitamin C treatment increases vascular tetrahydrobiopterin levels and nitric oxide synthase activity. Circ. Res., 2003, 92, 88-95.
182. Tóth, M.; Kukor, Z.; Valent, S. Chemical stabilization of tetrahydrobiopterin by L-ascorbic acid: contribution to placental endothelial nitric oxide synthase activity. Mol. Hum. Reprod., 2002, 8, 271-280.
183. Korhonen, R.; Lahti, A.; Kankaanranta, H.; Moilanen, E. Nitric oxide production and signaling in inflammation. Curr. Drug. Targets Inflamm. Allergy, 2005, 4, 471-479.
184. Coleman, J.W. Nitric oxide in immunity and inflammation. Int. Immunopharmacol., 2001, 1, 1397-406.
185. Hibbs, J.B.Jr. Infection and nitric oxide. J. Infect. Dis., 2002, 185, 9-17.
186. Isobe, K.; Nakashima, I. Feedback suppression of staphylococcal enterotoxin-stimulated T-lymphocyte proliferation by macrophages through inductive nitric oxide synthesis. Infect. Immun., 1992, 60, 4832-4837.
187. Isobe, K.; Nakashima, I. Nitric oxide production from a macrophage cell line: interaction with autologous and allogeneic lymphocytes. J. Cell. Biochem., 1993, 53, 198-205.
188. Albina, J.E.; Abate, J.A.; Henry, W.L.Jr. Nitric oxide production is required for murine resident peritoneal macrophages to suppress mitogen-stimulated T cell proliferation. Role of IFN-gamma in the induction of the nitric oxide-synthesizing pathway. J. Immunol., 1991, 147, 144-148.
189. Ahvazi, B.C.; Jacobs, P.; Stevenson, M.M. Role of macrophagederived nitric oxide in suppression of lymphocyte proliferation during blood-stage malaria. J. Leukoc. Biol., 1995, 58, 23-31.
190. Kawabe, T.; Isobe, K.I.; Hasegawa, Y.; Nakashima, I.; Shimokata, K. Immunosuppressive activity induced by nitric oxide in culture supernatant of activated rat alveolar macrophages. Immunology, 1992, 76, 72-78.
191. Denham, S.; Rowland, I.J. Inhibition of the reactive proliferation of lymphocytes by activated macrophages: the role of nitric oxide. Clin. Exp. Immunol., 1992, 87, 157-162.
192. Benbernou, N.; Esnault, S.; Shin, H.C.; Fekkar, H.; Guenounou, M. Differential regulation of IFN-gamma, IL-10 and inducible nitric oxide synthase in human T cells by cyclic AMP-dependent signal transduction pathway. Immunology, 1997, 91, 361-368.
193. Decoursey, T.E. Voltage-gated proton channels and other proton transfer pathways. Physiol. Rev., 2003, 83, 475-579.