Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: A randomized controlled pilot trial

• Published in: PloS one 2017-06, Vol.12 (6), p.e0179540-e0179540
• Main Authors: Carvalho, José Tarcisio G, Schneider, Marion, Cuppari, Lilian, Grabulosa, Caren C, T Aoike, Danilo, Q Redublo, Beata Marie, C Batista, Marcelo, Cendoroglo, Miguel, Maria Moyses, Rosa, Dalboni, Maria Aparecida
• Format: Article
• Language: English
• Subjects: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - blood; Biology and Life Sciences; Case-Control Studies; Cholecalciferol - pharmacology; Clinical trials; Cytokines; Cytokines - blood; Cytometry; Dialysis; Double-Blind Method; Enzymes; Fibroblasts; Flow cytometry; Genetic aspects; Growth factors; Hemodialysis; Homeostasis; Humans; Immune system; In vitro methods and tests; Inflammation; Inflammation - complications; Inflammation - prevention & control; Inflammation Mediators - blood; Interleukin 6; Intracellular; Kidney diseases; Lymphocytes; Lymphocytes B; Lymphocytes T; Medicine and Health Sciences; Nephrology; Patients; Physical sciences; Physiological aspects; Pilot Projects; Placebos; Prevention; Receptors, Calcitriol - blood; Supplementation; Supplements; TLR7 protein; TLR9 protein; Toll-like receptors; Toll-Like Receptors - blood; Uremia - complications; Uremia - enzymology; Vitamin D; Vitamin D - metabolism; Vitamin D receptors; Vitamin D3; Vitamin D3 24-Hydroxylase - blood
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0179540

It has been reported that vitamin D regulates the immune system. However, whether vitamin D repletion modulates inflammatory responses in lymphocytes from dialysis patients is unclear. In the clinical trial, thirty-two (32) dialysis patients with 25 vitamin D ≤ 20ng/mL were randomized to receive either supplementation of cholecalciferol 100,000 UI/week/3 months (16 patients) or placebo (16 patients). In the in vitro study, B and T lymphocytes from 12 healthy volunteers (HV) were incubated with or without uremic serum in the presence or absence of 25 or 1,25 vitamin D. We evaluated the intracellular expression of IL-6, IFN-γ TLR7, TLR9, VDR, CYP27b1 and CYP24a1 by flow cytometry. We observed a reduction in the expression of TLR7, TLR9, INF-γ and CYP24a1 and an increase in VDR and CYP27b1 expression in patients which were supplemented with cholecalciferol, whereas no differences were found in the placebo group. Uremic serum increased the intracellular expression of IL-6, IFN-γ, TLR7, TLR9, VDR, CYP27b1 and CYP24a1. Treatment with 25 or 1,25 vitamin D decreased IL-6 and TLR9. CYP24a1 silencing plus treatment with 25 and/or 1,25 vitamin D had an additional reduction effect on IL-6, IFN-γ, TLR7 and TLR9 expression. This is the first study showing that cholecalciferol repletion has an anti-inflammatory effect and improves vitamin D intracellular regulatory enzymes on lymphocytes from dialysis patients.