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

doi:10.1016/1043-4666(92)90012-G

Cytokine

Volume 4, Issue 6, November 1992, Pages 506-512

https://doi.org/10.1016/1043-4666(92)90012-G Get rights and content

Abstract

1,25-Dihydroxyvitamin D₃ [1,25-(OH)₂D₃] inhibits lymphocyte proliferation and production of antibodies and lymphokines such as interleukin ((IL)-2 and interferon γ. These lymphocyte functions are dependent upon cytokines, including IL-1α, IL-1β, IL-6 and tumour necrosis factor α (TNF-α), 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-α, IL-6 and TNF-α 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-α. 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.

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However, it remains to be a controversial issue among researchers. Some researchers believe that 1,25(OH)2D3 may limit B cell function mainly due to the repression of cytokine production by macrophage and monocytes or regulation of CD4+ T Cell response [115]. Some others are convinced that 1,25(OH)2D3 has an inhibitory effect on IgE production of B cells [116].
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1,25-dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level

Abstract

Lancet

Immunopharmacol

Biochem Biophys Res Commun

J Biol Chem

Blood

Cell Immunol

Cell Immunol

Blood

Immunol Today

Immunol Lett

Biochim Biophys Acta

The role of the vitamin D endocrine system in health and disease

N Engl J Med

The immunobiology of vitamin D

Immunol Today

Immunomodulating properties of 1,25-dihydroxyvitamin D3

Kidney Int

2,25-Dihydroxyvitamin D3 receptors in human leukocytes

Science

Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D3 (calcitriol)

J Clin Invest

1α,25-dihydroxyvitamin D3 and a novel vitamin D analogue MC 903 are potent inhibitors of human interleukin 1 in vitro

Immunol Lett

1α,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells

J Clin Invest

The effect of 1,25-dihydroxyvitamin D3 on in vitro immunoglobulin production in human B cells

J Immunol

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

Immunomodulating properties of 1,25-dihydroxyvitamin D₃

2,25-Dihydroxyvitamin D₃ receptors in human leukocytes

Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D₃ (calcitriol)

1α,25-dihydroxyvitamin D₃ and a novel vitamin D analogue MC 903 are potent inhibitors of human interleukin 1 in vitro

1α,25-dihydroxyvitamin D₃ suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells

The effect of 1,25-dihydroxyvitamin D₃ on in vitro immunoglobulin production in human B cells