Browse > Article
http://dx.doi.org/10.5115/acb.2010.43.4.294

Mega-dose vitamin C attenuated lung inflammation in mouse asthma model  

Jeong, Young-Joo (Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine)
Kim, Jin-Hee (Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine)
Kang, Jae-Seung (Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine)
Lee, Wang-Jae (Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine)
Hwang, Young-Il (Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine)
Publication Information
Anatomy and Cell Biology / v.43, no.4, 2010 , pp. 294-302 More about this Journal
Abstract
Asthma is a Th2-dependent disease mediated by IgE and Th2 cytokines, and asthmatic patients suffer from oxidative stresses from abnormal airway inflammation. Vitamin C is a micro-nutrient functioning as an antioxidant. When administered at a mega-dose, vitamin C has been reported to shift immune responses toward Th1. Thus, we tried to determine whether vitamin C exerted beneficial effects in asthma animal model. Asthma was induced in mice by sensitizing and challenging with ovalbumin. At the time of challenge, 3~5 mg of vitamin C was administered and the effects were evaluated. Vitamin C did not modulate Th1/Th2 balance in asthma model. However, it decreased airway hyperreactivity to methacholine, decreased inflammatory cell numbers in brochoalveolar lavage fluid, and moderate reduction of perivascular and peribronchiolar inflammatory cell infiltration. These results suggest that vitamin C administered at the time of antigen challenge exerted anti-inflammatory effects. Further studies based on chronic asthma model are needed to evaluate a long-term effect of vitamin C in asthma. In conclusion, even though vitamin C did not show any Th1/Th2 shifting effects in this experiment, it still exerted moderate anti-inflammatory effects. Considering other beneficial effects and inexpensiveness of vitamin C, mega-dose usage of vitamin C could be a potential supplementary modality for the management of asthma.
Keywords
Asthma; Vitamin C; Lung inflammation; Th1/Th2 balance;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Holgate ST, Holloway J, Wilson S, et al. (2006). Understanding the pathophysiology of severe asthma to generate new therapeutic opportunities. J Allergy Clin Immunol 117: 496-506   DOI   ScienceOn
2 Noh K, Lim H, Moon SK, et al. (2005). Mega-dose Vitamin C modulates T cell functions in Balb/c mice only when administered during T cell activation. Immunol Lett 98: 63-72   DOI   ScienceOn
3 Sackesen C, Ercan H, Dizdar E, et al. (2008). A comprehensive evaluation of the enzymatic and nonenzymatic antioxidant systems in childhood asthma. J Allergy Clin Immunol 122: 78-85   DOI   ScienceOn
4 Chang HH, Chen CS, Lin JY. (2009). High dose vitamin C supplementation increases the Th1/Th2 cytokine secretion ratio, but decreases eosinophilic infiltration in bronchoalveolar lavage fluid of ovalbumin-sensitized and challenged mice. J Agric Food Chem 57: 10471-10476   DOI   ScienceOn
5 Gao J, Gao X, Li W, Zhu Y, Thompson PJ. (2008). Observational studies on the effect of dietary antioxidants on asthma: a meta-analysis. Respirology 13: 528-536   DOI   ScienceOn
6 Scott DA, Poston RN, Wilson RF, Coward PY, Palmer RM. (2005). The influence of vitamin C on systemic markers of endothelial and inflammatory cell activation in smokers and non-smokers. Inflamm Res 54: 138-144   DOI   ScienceOn
7 Harik-Khan RI, Muller DC, Wise RA. (2004). Serum vitamin levels and the risk of asthma in children. Am J Epidemiol 159: 351-357   DOI   ScienceOn
8 Tulic MK, Hamid Q. (2006). New insights into the pathophysiology of the small airways in asthma. Clin Chest Med 27: 41-52   DOI   ScienceOn
9 Wannamethee SG, Lowe GD, Rumley A, Bruckdorfer KR, Whincup PH. (2006). Associations of vitamin C status, fruit and vegetable intakes, and markers of inflammation and hemostasis. Am J Clin Nutr 83: 567-574
10 Zhou J, Wolf CR, Henderson CJ, et al. (2008). Glutathione transferase P1: an endogenous inhibitor of allergic responses in a mouse model of asthma. Am J Respir Crit Care Med 178: 1202-1210   DOI   ScienceOn
11 Tagaya E, Tamaoki J. (2007). Mechanisms of airway remodeling in asthma. Allergol Int 56: 331-340   DOI   ScienceOn
12 Tecklenburg SL, Mickleborough TD, Fly AD, Bai Y, Stager JM. (2007). Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respir Med 101: 1770-1778   DOI   ScienceOn
13 Nelde A, Teufel M, Hahn C, et al. (2001). The impact of the route and frequency of antigen exposure on the IgE response in allergy. Int Arch Allergy Immunol 124: 461-469   DOI   ScienceOn
14 Schock BC, Young IS, Brown V, Fitch PS, Shields MD, Ennis M. (2003). Antioxidants and oxidative stress in BAL fluid of atopic asthmatic children. Pediatr Res 53: 375-381   DOI   ScienceOn
15 Noh K, Kim HG, Shin YA, et al. (2003). The effects of high-dose vitamin C administration on the cell-mediated immune response in mice. Immune Netw 3: 211-218   DOI
16 Rizzo MR, Abbatecola AM, Barbieri M, et al. (2008). Evidence for anti-inflammatory effects of combined administration of vitamin E and C in older persons with impaired fasting glucose: impact on insulin action. J Am Coll Nutr 27: 505-511   DOI
17 Maeda N, Hagihara H, Nakata Y, Hiller S, Wilder J, Reddick R. (2000). Aortic wall damage in mice unable to synthesize ascorbic acid. Proc Natl Acad Sci U S A 97: 841-846   DOI   ScienceOn
18 Marleau AM, Summers KL, Singh B. (2008). Differential contributions of APC subsets to T cell activation in nonobese diabetic mice. J Immunol 180: 5235-5249   DOI
19 McMillan SJ, Lloyd CM. (2004). Prolonged allergen challenge in mice leads to persistent airway remodelling. Clin Exp Allergy 34: 497-507   DOI   ScienceOn
20 Naidu KA. (2003). Vitamin C in human health and disease is still a mystery? An overview. Nutr J 2: 7   DOI   ScienceOn
21 Langlois M, Duprez D, Delanghe J, De Buyzere M, Clement DL. (2001). Serum vitamin C concentration is low in peripheral arterial disease and is associated with inflammation and severity of atherosclerosis. Circulation 103: 1863-1868   DOI   ScienceOn
22 Lee CW, Wang XD, Chien KL, et al. (2008). Vitamin C supplementation does not protect L-gulono-gamma-lactone oxidase-deficient mice from Helicobacter pylori-induced gastritis and gastric premalignancy. Int J Cancer 122: 1068-1076
23 Fogarty A, Lewis SA, Scrivener SL, et al. (2006). Corticosteroid sparing effects of vitamin C and magnesium in asthma: a randomised trial. Respir Med 100: 174-179   DOI   ScienceOn
24 Kaur B, Rowe BH, Arnold E. (2009). Vitamin C supplementation for asthma. Cochrane Database Syst Rev (1): CD000993
25 Kelly FJ, Mudway I, Blomberg A, Frew A, Sandstrom T. (1999). Altered lung antioxidant status in patients with mild asthma. Lancet 354: 482-483   DOI   ScienceOn
26 Kirby AC, Yrlid U, Svensson M, Wick MJ. (2001). Differential involvement of dendritic cell subsets during acute Salmonella infection. J Immunol 166: 6802-6811   DOI
27 Hamid Q, Tulic M. (2009). Immunobiology of asthma. Annu Rev Physiol 71: 489-507   DOI   ScienceOn
28 Hernandez M, Zhou H, Zhou B, et al. (2009). Combination treatment with high-dose vitamin C and alpha-tocopherol does not enhance respiratory-tract lining fluid vitamin C levels in asthmatics. Inhal Toxicol 21: 173-181   DOI   ScienceOn
29 Izuhara K, Ohta S, Shiraishi H, et al. (2009). The mechanism of mucus production in bronchial asthma. Curr Med Chem 16: 2867-2875   DOI   ScienceOn
30 Kamgar M, Zaldivar F, Vaziri ND, Pahl MV. (2009). Antioxidant therapy does not ameliorate oxidative stress and inflammation in patients with end-stage renal disease. J Natl Med Assoc 101: 336-344   DOI
31 Doherty T, Broide D. (2007). Cytokines and growth factors in airway remodeling in asthma. Curr Opin Immunol 19: 676-680   DOI   ScienceOn
32 Guaiquil VH, Vera JC, Golde DW. (2001). Mechanism of vitamin C inhibition of cell death induced by oxidative stress in glutathione-depleted HL-60 cells. J Biol Chem 276: 40955-40961   DOI   ScienceOn
33 Haines DD, Varga B, Bak I, et al. (2010). Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in Suppression of respiratory inflammation: a comparison with ibuprofen. Phytother Res [Epub ahead of Print]
34 Desai D, Brightling C. (2009). Cytokine and anti-cytokine therapy in asthma: ready for the clinic? Clin Exp Immunol 158: 10-19   DOI   ScienceOn
35 Cohn L, Tepper JS, Bottomly K. (1998). IL-4-independent induction of airway hyperresponsiveness by Th2, but not Th1, cells. J Immunol 161: 3813-3816
36 Du WD, Yuan ZR, Sun J, et al. (2003). Therapeutic efficacy of high-dose vitamin C on acute pancreatitis and its potential mechanisms. World J Gastroenterol 9: 2565-2569   DOI
37 Duan W, Chan JH, Wong CH, Leung BP, Wong WS. (2004). Anti-inflammatory effects of mitogen-activated protein kinase kinase inhibitor U0126 in an asthma mouse model. J Immunol 172: 7053-7059   DOI
38 Fogarty A, Lewis SA, Scrivener SL, et al. (2003). Oral magnesium and vitamin C supplements in asthma: a parallel group randomized placebo-controlled trial. Clin Exp Allergy 33: 1355-1359   DOI   ScienceOn
39 Carcamo JM, Pedraza A, Borquez-Ojeda O, Golde DW. (2002). Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation. Biochemistry 41: 12995-13002   DOI   ScienceOn
40 Chanez P, Wenzel SE, Anderson GP, et al. (2007). Severe asthma in adults: what are the important questions? J Allergy Clin Immunol 119: 1337-1348   DOI   ScienceOn
41 Broide DH. (2008). Immunologic and inflammatory mechanisms that drive asthma progression to remodeling. J Allergy Clin Immunol 121: 560-570   DOI   ScienceOn
42 Barrios RJ, Kheradmand F, Batts L, Corry DB. (2006). Asthma: pathology and pathophysiology. Arch Pathol Lab Med 130: 447-451
43 Bjermer L, Diamant Z. (2004). Current and emerging nonsteroidal anti-inflammatory therapies targeting specific mechanisms in asthma and allergy. Treat Respir Med 3: 235-246   DOI   ScienceOn