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Calcitriol effect on natural killer cells from hemodialyzed and normal subjects

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Abstract

Patients with chronic renal failure have a decreased secretion of calcitriol (CTR). They also show an impaired cellular immune response including a defective natural killer (NK) cell-mediated activity. The aim of this study was to analyze, in vivo and in vitro, the effect of CTR on NK cell cytotoxicity in healthy control subjects and in hemodialyzed (HD) patients. Our results show that HD patients had baseline-depressed NK cell activity when compared with controls (P<0.001), which increased significantly after 1 month of oral CTR treatment (0.5 μg/day) (P<0.001). Calcitriol treatment also induced a significant increase in CTR serum levels (P<0.001) and a significant decrease (P<0.001) in total parathyroid hormone (PTH). In vitro CTR treatment (10-7 M) of peripheral blood mononuclear cells (PBMC) increased NK cell-mediated cytotoxicity after 24 hours of incubation with a maximum at 48 hours (P<0.001). In vitro CTR treatment at doses of 10-11 and 10-9 M did not significantly increase NK cytotoxic activity. The enhanced NK activity after CTR treatment was not the consequence of increased numbers of CD56 positive cells, nor to lymphocyte activation, as tested by the expression of the interleukin 2 receptor p55 α chain (CD25) on their surface. In vitro treatment of PBMC from HD patients with CTR (10-7 M, during 48 hours) also induced a strong increase in NK cell cytotoxicity (P<0.001). These results demonstrate a positive role of CTR in the stimulation of NK cell activity and support the hypothesis of a direct steroid-mediated action of CTR on NK cells, although an indirect effect mediated by the CTR-induced PTH decrease in vivo cannot be excluded. Our data also raise the possibility for potential therapeutic uses of this hormone in immunomodulation of patients with depressed NK cell activity.

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Quesada, J.M., Serrano, I., Borrego, F. et al. Calcitriol effect on natural killer cells from hemodialyzed and normal subjects. Calcif Tissue Int 56, 113–117 (1995). https://doi.org/10.1007/BF00296341

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Key words

  • Calcitriol
  • Chronic renal failure
  • Cytotoxicity
  • Natural killer
  • PTH