Impact of High-Dose Vitamin D3 on Free Plasma 25-Hydroxyvitamin D Concentrations and Antimicrobial Peptides in Critically Ill Mechanically Ventilated Adults

Objectives High-dose vitamin D3 increases plasma total 25-hydroxyvitamin D [25(OH)D] in critically ill, ventilated patients, but the impact on plasma levels of free (non-protein bound) 25(OH)D, has not been investigated in critical illness. Moreover, the relationship of free 25(OH)D and regulation of endogenous antimicrobial peptides (AMPs) is unknown. Research Methods & Procedures In a double blind, randomized controlled trial, critically ill ventilator-dependent adults (n=30) received enteral vitamin D3 (250,000 or 500,000 IU total over 5 days) or placebo. Plasma was obtained serially for concentrations of free 25(OH)D, cathelicidin (LL-37), human beta-defensin-2 (hBD-2) and expression of peripheral blood mononuclear cell (PBMC) human cationic antimicrobial protein (hCAP18) mRNA. Total 25(OH)D and LL-37 concentrations and alveolar macrophage phagocytosis were determined in bronchoalveolar lavage fluid (BALF). Results Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (ρ=0.82, p< 0.001). The increase in free 25(OH)D was greatest with the 500,000 IU vitamin D3 dose compared to the lower dose. The percent change in mRNA expression of hCAP18 was positively associated with percent change in free 25(OH)D at day 7 and 14 (ρ=0.48, p=0.04 and ρ=0.59, p=0.03, respectively). In addition, plasma LL-37 levels correlated with the percentage of alveolar macrophages exhibiting phagocytosis (ρ=0.51, p = 0.04). Conclusions We found a dose-related increase in plasma free 25(OH)D levels, which was associated with increasing circulating mRNA expression of hCAP18 over time. There were no correlations between changes in total and free 25OH D, and plasma LL-37 and hBD-2 concentrations. Larger studies appear warranted to determine the impact of high-dose vitamin D3 administration on endogenous AMPs.