TY - JOUR

T1 - 1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level

AU - Müller, K

AU - Haahr, P M

AU - Diamant, M

AU - Rieneck, K

AU - Kharazmi, A

AU - Bendtzen, K

N1 - Keywords: Calcifediol; Calcitriol; Cytokines; Humans; Interleukin-1; Interleukin-6; Lipopolysaccharides; Monocytes; Protein Processing, Post-Translational; Superoxides; Tumor Necrosis Factor-alpha

PY - 1992

Y1 - 1992

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 1337987

VL - 4

SP - 506

EP - 512

JO - Cytokine

JF - Cytokine

SN - 1043-4666

IS - 6

ER -