1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level

Cytokine. 1992 Nov;4(6):506-12. doi: 10.1016/1043-4666(92)90012-g.


1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits lymphocyte proliferation and production of antibodies and lymphokines such as interleukin (IL)-2 and interferon gamma. These lymphocyte functions are dependent upon cytokines, including IL-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor alpha (TNF-alpha), produced by the antigen presenting cells. In the present study we examined the effect of 1,25-(OH)2D3 on the production of these cytokines, as well as superoxide generation by freshly isolated mononuclear cells and partially purified monocytes. The immediate precursor of 1,25(OH)2D3, 25-OH D3, and the synthetic analogue MC 903 ('Calcipotriol') were examined in parallel. 1,25-(OH)2D3 dose-dependently inhibited the production of IL-alpha, IL-6 and TNF-alpha by Escherichia coli lipopolysaccharide (LPS)-stimulated monocytes, without affecting superoxide production. MC 903 had comparable effects while 25-OH D3 was ineffective. The inhibition caused by 1,25-(OH)2D3 was not abolished by supraoptimal concentrations of LPS or indomethacin. 1,25-(OH)2D3 had similar effects on secreted and cell-associated IL-alpha. Nuclear run-off analysis indicated that inhibition of these cytokines was not caused by impaired production of mRNA. Taken together, the study demonstrates a vitamin D-induced inhibitory effect of LPS-driven monokine production, which is most likely a vitamin D-receptor mediated phenomenon exerted at a post-transcriptional, presecretory level. Impaired monokine production may be of importance in 1,25-(OH)2D3-mediated inhibition of lymphocyte functions in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcifediol / pharmacology
  • Calcitriol / analogs & derivatives
  • Calcitriol / pharmacology*
  • Cytokines / biosynthesis*
  • Cytokines / metabolism
  • Humans
  • In Vitro Techniques
  • Interleukin-1 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / metabolism
  • Protein Processing, Post-Translational / drug effects
  • Superoxides / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Superoxides
  • calcipotriene
  • Calcitriol
  • Calcifediol