Effects of high-dose cholecalciferol on serum markers of inflammation and immunity in patients with early chronic kidney disease.
OBJECTIVE
Vitamin D has anti-inflammatory and immune-regulating properties. We aimed to determine if high-dose cholecalciferol supplementation for 1 year in subjects with early chronic kidney disease (CKD) improved circulating markers of inflammation and immunity.


METHODS
In this double-blind, randomized, placebo-controlled trial, 46 subjects with early CKD (stages 2 and 3) were supplemented with oral cholecalciferol (50 000 IU weekly for 12 weeks followed by 50 000 IU every other week for 40 weeks) or a matching placebo for 1 year. Serum tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein-10 and neutrophil gelatinase-associated lipocalin were measured at baseline, 12 weeks and 1 year. Serum cathelicidin (LL-37) was measured at baseline and 12 weeks. An in vitro experiment was performed to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment on MCP-1 secretion in THP-1 monocytes activated with lipopolysaccharide (LPS) and Pseudomonas aeruginosa.


RESULTS
By 12 weeks, serum MCP-1 decreased in the cholecalciferol group (66.2±2.5 to 60.8±2.6 pg/ml, group-by-time interaction P=0.02) but was not different from baseline at 1 year. Other markers of inflammation and immunity did not change. In vitro, LPS- and Pseudomonas-activated monocytes treated with 1,25(OH)2D3 had significantly less MCP-1 secretion compared with untreated cells.


CONCLUSIONS
High-dose cholecalciferol decreased serum MCP-1 concentrations by 12 weeks in patients with early CKD, although the decrease was not maintained for the remainder of the year. In vitro results confirm an MCP-1-lowering effect of vitamin D. Future studies should determine if vitamin D-mediated reductions in MCP-1 concentrations reflect improved clinical outcomes.
Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
J A
JA
Alvarez
S M
SM
Zughaier
J
J
Law
L
L
Hao
H
H
Wasse
T R
TR
Ziegler
V
V
Tangpricha
D000284:Administration, Oral; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000097:blood; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007249:Inflammation / Q000097:blood* / Q000188:drug therapy; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives; D054804:Cathelicidins
D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D002762:Cholecalciferol; D007371:Interferon-gamma; D054804:Cathelicidins