Effect of High‐Dose Vitamin D on Antimicrobial Peptides in Ventilator‐Dependent Critically Ill Patients

Abstract

ObjectiveVitamin D has been shown to influence indexes of immunity, including antimicrobial peptides (AMPs). Vitamin D deficiency is common in critical illness, but the impact of vitamin D status or the response to treatment with high‐dose vitamin D on AMPs in this population is unknown. Thus, we evaluated the impact of two doses of vitamin D3 (D3) versus placebo on AMPs in ventilated, critically ill subjects.MethodsThirty critically ill, ventilated subjects were enrolled in a randomized, double‐blind controlled trial of enteral high‐dose D3 (total dose = 250,000 IU or 500,000 IU) given in divided doses over 5 consecutive days. Plasma 25‐hydroxyvitamin D [25(OH)D] was measured by chemiluminescence. Plasma levels of AMPs, cathelicidin (LL‐37) and human beta‐defensin‐2 (hBD‐2), were measured by ELISA, and PBMC LL‐37 mRNA by quantitative PCR at baseline, days 7 and 14 after study entry. Descriptive statistics (mean ± SD), Spearman correlations, and repeated measures ANOVA were used for analysis.ResultsThe study population was 60% male, mean age was 63.5 ± 17.3 yrs, and 43% were vitamin D deficient at baseline. D3 administration significantly increased plasma 25(OH)D levels from baseline to day 14 vs placebo (500,000 IU: 20.0 ± 7.3 to 62.4 ± 16.7 ng/mL; 250,000 IU: 23.2 ± 7.8 to 50.4 ± 29.4 ng/mL; placebo: 21.5 ± 12.2 to 21.5 ± 11.3 ng/mL, respectively; p < 0.01). Baseline 25(OH)D levels were unrelated to baseline AMP indexes. Plasma LL‐37, hBD‐2, and PBMC LL‐37 mRNA did not change over time in any group.ConclusionsBaseline vitamin D status did not influence plasma LL‐37 and hBD‐2 levels or PBMC LL‐37 mRNA in critically ill, ventilated adults. High‐dose D3 administration markedly increased 25(OH)D levels, but did not alter production of AMPs.