Skip to main content
Immunology logoLink to Immunology
. 1991 Aug;73(4):466–471.

Impairment of cytokine production in mice fed a vitamin D3-deficient diet.

M Kankova 1, W Luini 1, M Pedrazzoni 1, F Riganti 1, M Sironi 1, B Bottazzi 1, A Mantovani 1, A Vecchi 1
PMCID: PMC1384578  PMID: 1655638

Abstract

C57Bl/6 female mice fed a Vitamin D (VIT-D)-deficient diet had serum levels of 25-hydroxyvitamin D decreasing with the time of diet exposure (3 and 8 weeks). Cytokine production (IL-6, TNF and IL-1) by peritoneal macrophages cultured in vitro with a standard stimulus, LPS, evaluated in the supernatants as biological activity, was significantly reduced in VIT-D-deficient animals. The defect in monokine production was partial and was evident at suboptimal LPS concentrations and incubation times. I-A antigen expression, induced in macrophages by in vitro exposure to IFN-gamma, was not modified in VIT-D-deficient mice, but IFN-gamma-inducible macrophage cytotoxicity to tumour target cells was significantly decreased in VIT-D-deficient animals. Moreover, basal and Poly I:C-induced NK activity was not modified by VIT-D deficiency. Thus, macrophage functions, such as cytokine production and tumour cytotoxicity induction, are down-modulated in vitro by VIT-D deprivation. To give more support to the relevance of VIT-D availability for cytokine production, TNF and IL-6 have been evaluated in the sera of control and VIT-D-deficient mice given LPS as a model stimulus. Serum peak levels of both cytokines were at least halved in VIT-D-deprived mice. Thus, VIT-D deficiency may represent a model of partial defect of monokine production.

Full text

PDF
467

Selected References

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

  1. 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]
  2. Adams J. S., Sharma O. P., Gacad M. A., Singer F. R. Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis. J Clin Invest. 1983 Nov;72(5):1856–1860. doi: 10.1172/JCI111147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aggarwal B. B., Moffat B., Harkins R. N. Human lymphotoxin. Production by a lymphoblastoid cell line, purification, and initial characterization. J Biol Chem. 1984 Jan 10;259(1):686–691. [PubMed] [Google Scholar]
  4. Baccarini M., Bistoni F., Lohmann-Matthes M. L. Organ-associated macrophage precursor activity: isolation of candidacidal and tumoricidal effectors from the spleens of cyclophosphamide-treated mice. J Immunol. 1986 Feb 1;136(3):837–843. [PubMed] [Google Scholar]
  5. Bar-Shavit Z., Noff D., Edelstein S., Meyer M., Shibolet S., Goldman R. 1,25-dihydroxyvitamin D3 and the regulation of macrophage function. Calcif Tissue Int. 1981;33(6):673–676. doi: 10.1007/BF02409507. [DOI] [PubMed] [Google Scholar]
  6. Bar-Shavit Z., Teitelbaum S. L., Reitsma P., Hall A., Pegg L. E., Trial J., Kahn A. J. Induction of monocytic differentiation and bone resorption by 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5907–5911. doi: 10.1073/pnas.80.19.5907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Belsey R. E., DeLuca H. F., Potts J. T., Jr A rapid assay for 25-OH-vitamin D3 without preparative chromatography. J Clin Endocrinol Metab. 1974 Jun;38(6):1046–1051. doi: 10.1210/jcem-38-6-1046. [DOI] [PubMed] [Google Scholar]
  8. Boraschi D., Censini S., Tagliabue A. Macrophage antitumor activity: impaired responsiveness to interferon-gamma of macrophages from genetically defective mice. Eur J Immunol. 1984 Nov;14(11):1061–1063. doi: 10.1002/eji.1830141119. [DOI] [PubMed] [Google Scholar]
  9. Colotta F., Peri G., Villa A., Mantovani A. Rapid killing of actinomycin D-treated tumor cells by human mononuclear cells. I. Effectors belong to the monocyte-macrophage lineage. J Immunol. 1984 Feb;132(2):936–944. [PubMed] [Google Scholar]
  10. Dinarello C. A. Interleukin-1 and its biologically related cytokines. Adv Immunol. 1989;44:153–205. doi: 10.1016/s0065-2776(08)60642-2. [DOI] [PubMed] [Google Scholar]
  11. Gavison R., Bar-Shavit Z. Impaired macrophage activation in vitamin D3 deficiency: differential in vitro effects of 1,25-dihydroxyvitamin D3 on mouse peritoneal macrophage functions. J Immunol. 1989 Dec 1;143(11):3686–3690. [PubMed] [Google Scholar]
  12. Girasole G., Wang J. M., Pedrazzoni M., Pioli G., Balotta C., Passeri M., Lazzarin A., Ridolfo A., Mantovani A. Augmentation of monocyte chemotaxis by 1 alpha,25-dihydroxyvitamin D3. Stimulation of defective migration of AIDS patients. J Immunol. 1990 Oct 15;145(8):2459–2464. [PubMed] [Google Scholar]
  13. Haddad J. G., Chyu K. J. Competitive protein-binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinol Metab. 1971 Dec;33(6):992–995. doi: 10.1210/jcem-33-6-992. [DOI] [PubMed] [Google Scholar]
  14. Haussler M. R., McCain T. A. Basic and clinical concepts related to vitamin D metabolism and action (first of two parts). N Engl J Med. 1977 Nov 3;297(18):974–983. doi: 10.1056/NEJM197711032971804. [DOI] [PubMed] [Google Scholar]
  15. Hopkins S. J., Humphreys M. Simple, sensitive and specific bioassay of interleukin-1. J Immunol Methods. 1989 Jun 21;120(2):271–276. doi: 10.1016/0022-1759(89)90252-4. [DOI] [PubMed] [Google Scholar]
  16. Lohmann-Matthes M. L., Domzig W., Roder J. Promonocytes have the functional characteristics of natural killer cells. J Immunol. 1979 Oct;123(4):1883–1886. [PubMed] [Google Scholar]
  17. Luini W., Boraschi D., Alberti S., Aleotti A., Tagliabue A. Morphological characterization of a cell population responsible for natural killer activity. Immunology. 1981 Aug;43(4):663–668. [PMC free article] [PubMed] [Google Scholar]
  18. Mantovani A., Luini W., Candiani G. P., Spreafico F. Effect of chemotherapeutic agents on natural and BCG-stimulated macrophage cytotoxicity in mice. Int J Immunopharmacol. 1980;2(4):333–339. doi: 10.1016/0192-0561(80)90033-8. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Miyaura C., Abe E., Nomura H., Nishii Y., Suda T. 1 alpha,25-Dihydroxyvitamin D3 suppresses proliferation of murine granulocyte-macrophage progenitor cells (CFU-C). Biochem Biophys Res Commun. 1982 Oct 29;108(4):1728–1733. doi: 10.1016/s0006-291x(82)80111-3. [DOI] [PubMed] [Google Scholar]
  21. Norman A. W., Roth J., Orci L. The vitamin D endocrine system: steroid metabolism, hormone receptors, and biological response (calcium binding proteins). Endocr Rev. 1982 Fall;3(4):331–366. doi: 10.1210/edrv-3-4-331. [DOI] [PubMed] [Google Scholar]
  22. Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
  23. Peri G., Rossi V., Taraboletti G., Erroi A., Mantovani A. Ia antigen expression and IL-1 activity in murine tumour-associated macrophages. Immunology. 1986 Dec;59(4):527–533. [PMC free article] [PubMed] [Google Scholar]
  24. Provvedini D. M., Deftos L. J., Manolagas S. C. 1,25-Dihydroxyvitamin D3 promotes in vitro morphologic and enzymatic changes in normal human monocytes consistent with their differentiation into macrophages. Bone. 1986;7(1):23–28. doi: 10.1016/8756-3282(86)90148-1. [DOI] [PubMed] [Google Scholar]
  25. Provvedini D. M., Tsoukas C. D., Deftos L. J., Manolagas S. C. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science. 1983 Sep 16;221(4616):1181–1183. doi: 10.1126/science.6310748. [DOI] [PubMed] [Google Scholar]
  26. Rigby W. F., Noelle R. J., Krause K., Fanger M. W. The effects of 1,25-dihydroxyvitamin D3 on human T lymphocyte activation and proliferation: a cell cycle analysis. J Immunol. 1985 Oct;135(4):2279–2286. [PubMed] [Google Scholar]
  27. Rook G. A., Taverne J., Leveton C., Steele J. The role of gamma-interferon, vitamin D3 metabolites and tumour necrosis factor in the pathogenesis of tuberculosis. Immunology. 1987 Oct;62(2):229–234. [PMC free article] [PubMed] [Google Scholar]
  28. Sironi M., Breviario F., Proserpio P., Biondi A., Vecchi A., Van Damme J., Dejana E., Mantovani A. IL-1 stimulates IL-6 production in endothelial cells. J Immunol. 1989 Jan 15;142(2):549–553. [PubMed] [Google Scholar]
  29. Ströder J., Kasal P. Evaluation of phagocytosis in rickets. Acta Paediatr Scand. 1970 May;59(3):288–292. doi: 10.1111/j.1651-2227.1970.tb09005.x. [DOI] [PubMed] [Google Scholar]
  30. Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–278. doi: 10.1146/annurev.iy.08.040190.001345. [DOI] [PubMed] [Google Scholar]
  31. van der Meer J. W., Barza M., Wolff S. M., Dinarello C. A. A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1620–1623. doi: 10.1073/pnas.85.5.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. van der Meer J. W. The effects of recombinant interleukin-1 and recombinant tumor necrosis factor on non-specific resistance to infection. Biotherapy. 1988;1(1):19–25. doi: 10.1007/BF02170132. [DOI] [PubMed] [Google Scholar]

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

RESOURCES