Cholecalciferol supplementation alters calcitriol-responsive monocyte proteins and decreases inflammatory cytokines in ESRD.
In vitro, monocyte 1alpha-hydroxylase converts 25-hydroxyvitamin D [25(OH)D] to 1,25-dihydroxyvitamin D to regulate local innate immune responses, but whether 25(OH)D repletion affects vitamin D-responsive monocyte pathways in vivo is unknown. Here, we identified seven patients who had 25(OH)D insufficiency and were undergoing long-term hemodialysis and assessed changes after cholecalciferol and paricalcitol therapies in both vitamin D-responsive proteins in circulating monocytes and serum levels of inflammatory cytokines. Cholecalciferol therapy increased serum 25(OH)D levels four-fold, monocyte vitamin D receptor expression three-fold, and 24-hydroxylase expression; therapy decreased monocyte 1alpha-hydroxylase levels. The CD16(+) "inflammatory" monocyte subset responded to 25(OH)D repletion the most, demonstrating the greatest increase in vitamin D receptor expression after cholecalciferol. Cholecalciferol therapy reduced circulating levels of inflammatory cytokines, including IL-8, IL-6, and TNF. These data suggest that nutritional vitamin D therapy has a biologic effect on circulating monocytes and associated inflammatory markers in patients with ESRD.
Stubbs
Jason R
JR
3901 Rainbow Boulevard, MS 3002, Kansas City, KS 66160, USA. jstubbs@kumc.edu
Idiculla
Arun
A
Slusser
Joyce
J
Menard
Rochelle
R
Quarles
L Darryl
LD
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism*; D002762:Cholecalciferol / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism*; D019587:Dietary Supplements; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000378:metabolism; D006435:Renal Dialysis; D013250:Steroid Hydroxylases / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000188:drug therapy / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D018167:Receptors, Calcitriol; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D054804:Cathelicidins