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Effect of Vitamin D3 on Phagocytic Potential of Macrophages with Live Mycobacterium tuberculosis and Lymphoproliferative Response in Pulmonary Tuberculosis

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Abstract

Immune responses are elicited through antigen presentation and recognition by macrophages and T-lymphocytes, respectively. The immunomodulatory effect of vitamin D3 on macrophage phagocytic potential with live Mycobacterium tuberculosis, spontaneous and M. tuberculosis culture filtrate antigen induced lymphocyte responses were studied in pulmonary tuberculosis patients (PTBPs) (n = 31) and normal healthy subjects (NHSs) (n = 43). Vitamin D3 at a concentration of 10−7 M significantly enhanced the macrophage phagocytosis of live M. tuberculosis in normal subjects with low phagocytic potential (less than 10%) (p = 0.015). No such increase was observed in PTBPs. Vitamin D3 significantly decreased the spontaneous lymphoproliferative response (p = 0.022) and increased the apoptosis of peripheral blood mononuclear cells in PTBPs (p = 0.024). In normals, vitamin D3 increased the spontaneous lymphoproliferative response. An inverse correlation between macrophage phagocytosis and spontaneous response was observed in NHSs, whereas a direct correlation was seen between vitamin D3-treated cells in normal subjects under in vitro condition. Vitamin D3 decreased the M. tuberculosis culture filtrate antigen induced lymphocyte response significantly in normal subjects (p = 0.0003), while it had no influence on the lymphocyte response in PTBPs. The present study suggests that exposure to vitamin D3 increases the phagocytic potential and spontaneous lymphoproliferative response but brings down the antigen-induced response in normals. In tuberculosis, addition of vitamin D3 has no significant effect on antigen-induced lymphoproliferative response. This may be due to the unresponsive nature of the cells to the action of vitamin D3 by virtue of the disease, which renders them inactive.

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REFERENCES

  1. Kaufmann SH: Protection against tuberculosis: Cytokines, T cells, and macrophages. Ann Rheum Dis 61(Suppl 2:ii):54-58, 2002

    Google Scholar 

  2. Dowling GB, Prosser-Thomas EW: Treatment of lupus vulgaris with calciferol. Lancet 1:919-922, 1946

    Google Scholar 

  3. Sharma OP: Hypercalcemia in granulomatous disorders: A clinical review. Curr Opin Pulm Med 6:442-447, 2000

    Google Scholar 

  4. Sharma SC: Serum calcium in pulmonary tuberculosis. Postgrad Med J 57:694-696, 1981

    Google Scholar 

  5. Davies PD, Brown RC, Church HA, Woodhead JS: The effect of anti-tuberculosis chemotherapy on vitamin D and calcium metabolism. Tubercle 68:261-266, 1987

    Google Scholar 

  6. Chan TY, Poon P, Pang J, Swaminathan R, Chan CH, Nisar M, Williams CS, Davies PD: A study of the calcium and vitamin D metabolism in Chinese patients with pulmonary tuberculosis. J Trop Med Hyg 97:26-30, 1994

    Google Scholar 

  7. Liam CK, Lim KH, Srinivas P, Poi PJ: Hypercalcaemia in patients with newly diagnosed tuberculosis in Malaysia. Int J Tuberc Lung Dis 2:818-823, 1998

    Google Scholar 

  8. Roussos A, Lagogianni I, Gonis A, Ilias I, Kazi D, Patsopoulos D, Philippou N: Hypercalcaemia in Greek patients with tuberculosis before the initiation of anti-tuberculosis treatment. Respir Med 95:187-190, 2001

    Google Scholar 

  9. Abbasi AA, Chemplavil JK, Farah S, Muller BF, Arnstein AR: Hypercalcemia in active pulmonary tuberculosis. Ann Intern Med 90:324-328, 1979

    Google Scholar 

  10. Need AG, Phillips PJ, Chiu FTS, Prisk HM: Hypercalcaemia associated with tuberculosis. BMJ 280:831, 1980

    Google Scholar 

  11. Chan TY, Chan CH, Shek CC: The prevalence of hypercalcaemia in pulmonary and miliary tuberculosis—a longtitudinal study. Singapore Med J 35:613-615, 1994

    Google Scholar 

  12. Davies PD, Church HA, Brown RC, Woodhead JS: Raised serum calcium in tuberculosis patients in Africa. Eur J Respir Dis 71:341-344, 1987

    Google Scholar 

  13. Chan TY, Chan CH, Shek CC, Davies PD: Hypercalcemia in active pulmonary tuberculosis and its occurrence in relation to the radiographic extent of disease. Southeast Asian J Trop Med Public Health 23:702-704, 1992

    Google Scholar 

  14. Reichel H, Koeffler HP, Barbers R, Norman AW: Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis. J Clin Endocrinol Metab 65:1201-1209, 1987

    Google Scholar 

  15. Cadranel J, Hance AJ, Milleron B, Paillard F, Akown GM, Garabedian M: Vitamin D metabolism in tuberculosis: Production of 1,25 (OH)2D3 by cells recovered by bronchoalveolar lavage and the role of this metabolite in calcium homeostasis. Am Rev Respir Dis 138:984-989, 1988

    Google Scholar 

  16. Cadranel J, Garabedian M, Milleron B, Guillozo H, Akoun G, Hance AJ: 1,25 (OH)2D3 production by T lymphocytes and alveolar macrophages recovered by lavage from normocalcemie patients with tuberculosis. J Clin Invest 85:1588-1593, 1990

    Google Scholar 

  17. Lemire JM: Immunomodulatory actions of 1,25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol 53:599-602, 1995

    Google Scholar 

  18. Rook GA, Steele J, Fraher L, Barker S, Karmali R, O'Riordan J, Stanford J: Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology 57:159-163, 1986

    Google Scholar 

  19. Piemonti L, Monti P, Sironi M, Fraticelli P, Leone BE, Dal Cin E, Allavena P, Di Carlo V: Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. J Immunol 164:4443-4451, 2000

    Google Scholar 

  20. D'Ambrosio D, Cippitelli M, Cocciolo MG, Mazzeo D, Di Lucia P, Lang R, Sinigaglia F, Panina-Bordignon P: Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J Clin Invest 101:252-262, 1998

    Google Scholar 

  21. Penna G, Adorini L: 1 Alpha, 25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 164:2405-2411, 2000

    Google Scholar 

  22. Muller K, Odum N, Bendtzen K: 1,25-Dihydroxyvitamin D3 selectively reduces interleukin-2 levels and proliferation of human T cell lines in vitro. Immunol Lett 35:177-182, 1993

    Google Scholar 

  23. Malloy PJ, Feldman D: Vitamin D resistance. Am J Med 106:355-370, 1999

    Google Scholar 

  24. Zabaleta J, Arias M, Maya JR, Garcia LF: Diminished adherence and/or ingestion of virulent Mycobacterium tuberculosis by monocyte-derived macrophages from patients with tuberculosis. Clin Diagn Lab Immunol 5:690-694, 1998

    Google Scholar 

  25. Selvaraj P, Kurian SM, Uma H, Reetha AM, Narayanan PR: Influence of non-MHC genes on lymphocyte response to Mycobacterium tuberculosis antigens &; tuberculin reactive status in pulmonary tuberculosis. Indian J Med Res 112:86-92, 2000

    Google Scholar 

  26. Placido R, Mancino G, Amendola A, Mariani F, Vendetti S, Piacentini M, Sanduzzi A, Bocchino ML, Zembala M, Colizzi V: Apoptosis of human monocytes/macrophages in Mycobacterium tuberculosis infection. J Pathol 181:31-38, 1997

    Google Scholar 

  27. Barnes PF, Chatterjee D, Abrams JS, Lu S, Wang E, Yamamura M, Brennan PJ, Modlin RL: Cytokine production induced by Mycobacterium tuberculosis lipo-arabinomannan. Relationship to chemical structure. J Immunol 149:541-547, 1992

    Google Scholar 

  28. Lin Y, Zhang M, Hofman FM, Gong J, Barnes PF: Absence of a prominent Th2 cytokine response in human tuberculosis. Infect Immun 64:1351-1356, 1996

    Google Scholar 

  29. Wang P, Wu P, Siegel MI, Egan RW, Billah MM: IL-10 inhibits transcription of cytokine genes in human peripheral blood mononuclear cells. J Immunol 153:811-816, 1994

    Google Scholar 

  30. Toossi Z, Gogate P, Shiratsuchi H, Young T, Ellner JJ: Enhanced production of TGF-beta by blood monocytes from patients with active tuberculosis and presence of TGF-beta in tuberculous granulomatous lung lesions. J Immunol 154:465-473, 1995

    Google Scholar 

  31. Hirsch CS, Yoneda T, Averill L, Ellner JJ, Toossi Z: Enhancement of intracellular growth of Mycobacterium tuberculosis in human monocytes by transforming growth factor-beta 1. J Infect Dis 170:1229-1237, 1994

    Google Scholar 

  32. Tsoukas CD, Provvedini DM, Manolagas SC: 1,25-Dihydroxyvitamin D3: A novel immunoregulatory hormone. Science 224:1438-1440, 1984

    Google Scholar 

  33. Lemire JM, Adams JS, Sakai R, Jordan SC: 1 Alpha, 25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells. J Clin Invest 74:657-661, 1984

    Google Scholar 

  34. Casteels K, Bouillon R, Waer M, Mathieu C: Immunomodulatory effects of 1,25-dihydroxyvitamin D3. Curr Opin Nephrol Hypertens 4:313-318, 1995

    Google Scholar 

  35. Rigby WF, Waugh M, Graziano RF: Regulation of human monocyte HLA-DR and CD4 antigen expression, and antigen presentation by 1,25-dihydroxyvitamin D3. Blood 76:189-197, 1990

    Google Scholar 

  36. Rook GAW: The role of vitamin D in tuberculosis. Am Rev Respir Dis 138:768-770, 1988

    Google Scholar 

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Authors and Affiliations

  1. Tuberculosis Research Centre, Indian Council of Medical Research, Chennai, India

    G. Chandra, P. Selvaraj, M. S. Jawahar, V. V. Banurekha & P. R. Narayanan

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  1. G. Chandra
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  2. P. Selvaraj
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  3. M. S. Jawahar
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  4. V. V. Banurekha
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  5. P. R. Narayanan
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Chandra, G., Selvaraj, P., Jawahar, M.S. et al. Effect of Vitamin D3 on Phagocytic Potential of Macrophages with Live Mycobacterium tuberculosis and Lymphoproliferative Response in Pulmonary Tuberculosis. J Clin Immunol 24, 249–257 (2004). https://doi.org/10.1023/B:JOCI.0000025446.44146.52

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  • DOI: https://doi.org/10.1023/B:JOCI.0000025446.44146.52

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