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We previously observed that critically ill patients are vitD deficient. This status cannot be restored by increasing the normally recommended intravenous vitD dose. The antimicrobial peptide LL-37 is expressed in macrophages upon stimulation by 25OHD3. sCD163 is a soluble pattern-recognition receptor, which is a marker of macrophage activation and a predictor of mortality in SIRS. The aim of this study is to unravel the impact of 25OHD3 deficiency and normalization on innate immunity parameters - CRP, LL-37 and sCD163 - in critical illness.
We randomly allocated patients upon ICU admission to receive either placebo (n = 13) or a 10-day treatment of 15 μg/day 25OHD3 intravenously after a loading dose of 200 μg intravenously (n = 11) on top of the normal vitD dose (200 IU). Patients with chronic bone or kidney disease, glucocorticoid treatment, age younger than 18 years, or with an anticipated ICU length of stay less than 10 days were excluded. On admission, patients were compared with healthy age-matched, gendermatched and BMI-matched controls (n = 24).
Administration of the 25OHD3 regimen resulted in a rapid and sustained increase of serum 25OHD3 levels (P < 0.05 vs placebo). 1,25(OH)2D3 levels rose only transiently (P = 0.07 on day 1, P = 0.08 on day 2 vs placebo). 25OHD3 and 1,25(OH)2D3 levels were lower than those of healthy controls (sampled during summer). 25OHD3 treatment had no significant effect on CRP. On admission, LL-37 levels (26 ± 6 μg/l) were comparable with those of healthy controls (22 ± 2 μg/l). The treatment tended to transiently increase LL-37 levels (change from baseline: P = 0.1 on day 6 vs placebo). Serum sCD163 levels tended to be higher at baseline (P = 0.06 vs healthy controls) and rose significantly over time (P < 0.05 on day 5 and on day 10 vs day 0) but were not influenced by the treatment.
The preliminary results of this randomized placebocontrolled pilot study indicate that, in contrast to a high intravenous 500 IU vitD supplement, intravenous 25OHD3 treatment resulted in an immediate and persistent increase in serum 25OHD3, but did not affect 1,25(OH)2D3 levels. Plasma LL-37 alterations in the studied prolonged critically ill patients hints at ameliorated LL-37 production provided that the 25OHD3 status is restored. Serum sCD163 and CRP levels evolved during the ICU stay, but were not significantly altered by 25OHD3 supplementation. The results of this pilot study warrant further research into the potential modulation of innate immune processes by 25OHD3 in the critically ill.