Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1986 Jan;57(1):159–163.

Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes.

G A Rook, J Steele, L Fraher, S Barker, R Karmali, J O'Riordan, J Stanford
PMCID: PMC1453883  PMID: 3002968

Abstract

Previous studies have shown that recombinant interferon gamma (IFN-gamma), crude T cell supernatants, or appropriate T-cell lines can cause total inhibition of the growth of M. tuberculosis inside murine peritoneal macrophages. In similar experiments with human monocytes much smaller effects are seen. This could be due to the relative immaturity of these cells. Because dihydroxy vitamin D3 (1,25-(OH)2 D3) can cause phenotypic differentiation of immature leukemic lines into macrophage-like cells, we have explored the possibility that exposure to cholecalciferol metabolites in vitro might increase the ability of monocytes to control proliferation of M. tuberculosis, or cause monocytes to mature into cells able to respond appropriately to IFN-gamma. Incubation of monocytes with three cholecalciferol metabolites induced anti-tuberculosis activity to an extent that correlated with their binding affinities to the intracellular receptor protein for the derivatives. 1,25-(OH)2 D3 also primed monocytes for phorbol myristate acetate-triggered reduction of nitroblue tetrazolium. The effects were additive rather than synergistic with those of IFN-gamma. Monocytes incubated with IFN-gamma developed 25-OH D3 1-hydroxylase activity, detected by conversion of tritiated 25-(OH) D3 to a more polar metabolite which coeluted with 1,25-(OH)2 D3 on straight and reverse-phase HPLC. The latter is a more active form in vivo. These findings help to explain claims for the efficacy of vitamin D in the treatment of some forms of tuberculosis, and also the occasional finding of raised serum calcium, and disturbed vitamin D metabolism in these patients.

Full text

PDF
159

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbasi A. A., Chemplavil J. K., Farah S., Muller B. F., Arnstein A. R. Hypercalcemia in active pulmonary tuberculosis. Ann Intern Med. 1979 Mar;90(3):324–328. doi: 10.7326/0003-4819-90-3-324. [DOI] [PubMed] [Google Scholar]
  2. Abe E., Miyaura C., Sakagami H., Takeda M., Konno K., Yamazaki T., Yoshiki S., Suda T. Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4990–4994. doi: 10.1073/pnas.78.8.4990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Adams J. S., Gacad M. A. Characterization of 1 alpha-hydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis. J Exp Med. 1985 Apr 1;161(4):755–765. doi: 10.1084/jem.161.4.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brincourt J. Le calciférol a-t-il une action liquéfiante sur le caséum. Poumon Coeur. 1967;23(7):841–851. [PubMed] [Google Scholar]
  5. Epstein S., Stern P. H., Bell N. H., Dowdeswell I., Turner R. T. Evidence for abnormal regulation of circulating 1 alpha, 25-dihydroxyvitamin D in patients with pulmonary tuberculosis and normal calcium metabolism. Calcif Tissue Int. 1984 Sep;36(5):541–544. doi: 10.1007/BF02405362. [DOI] [PubMed] [Google Scholar]
  6. FANIELLE G. La D-vitaminothérapie massive. Brux Med. 1951 Jul 15;31(28):1475–1485. [PubMed] [Google Scholar]
  7. Grange J. M., Davies P. D., Brown R. C., Woodhead J. S., Kardjito T. A study of vitamin D levels in Indonesian patients with untreated pulmonary tuberculosis. Tubercle. 1985 Sep;66(3):187–191. doi: 10.1016/0041-3879(85)90035-2. [DOI] [PubMed] [Google Scholar]
  8. Kochan I. The role of iron in bacterial infections, with special consideration of host-tubercle bacillus interaction. Curr Top Microbiol Immunol. 1973;60:1–30. doi: 10.1007/978-3-642-65502-9_1. [DOI] [PubMed] [Google Scholar]
  9. Koeffler H. P., Reichel H., Bishop J. E., Norman A. W. gamma-Interferon stimulates production of 1,25-dihydroxyvitamin D3 by normal human macrophages. Biochem Biophys Res Commun. 1985 Mar 15;127(2):596–603. doi: 10.1016/s0006-291x(85)80202-3. [DOI] [PubMed] [Google Scholar]
  10. Mangelsdorf D. J., Koeffler H. P., Donaldson C. A., Pike J. W., Haussler M. R. 1,25-Dihydroxyvitamin D3-induced differentiation in a human promyelocytic leukemia cell line (HL-60): receptor-mediated maturation to macrophage-like cells. J Cell Biol. 1984 Feb;98(2):391–398. doi: 10.1083/jcb.98.2.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Miyaura C., Abe E., Kuribayashi T., Tanaka H., Konno K., Nishii Y., Suda T. 1 alpha,25-Dihydroxyvitamin D3 induces differentiation of human myeloid leukemia cells. Biochem Biophys Res Commun. 1981 Oct 15;102(3):937–943. doi: 10.1016/0006-291x(81)91628-4. [DOI] [PubMed] [Google Scholar]
  12. Narang N. K., Gupta R. C., Jain M. K. Role of vitamin D in pulmonary tuberculosis. J Assoc Physicians India. 1984 Feb;32(2):185–188. [PubMed] [Google Scholar]
  13. Rook G. A., Champion B. R., Steele J., Varey A. M., Stanford J. L. I-A restricted activation by T cell lines of anti-tuberculosis activity in murine macrophages. Clin Exp Immunol. 1985 Feb;59(2):414–420. [PMC free article] [PubMed] [Google Scholar]
  14. Rook G. A., Steele J., Umar S., Dockrell H. M. A simple method for the solubilisation of reduced NBT, and its use as a colorimetric assay for activation of human macrophages by gamma-interferon. J Immunol Methods. 1985 Sep 3;82(1):161–167. doi: 10.1016/0022-1759(85)90235-2. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES