Impact of high-dose vitamin D3 on plasma free 25-hydroxyvitamin D concentrations and antimicrobial peptides in critically ill mechanically ventilated adults

High-dose vitamin D3 increases plasma total 25-hydroxyvitamin D [25(OH)D] in critically ill, ventilated patients; however, to our knowledge, the effect on plasma levels of free (nonprotein-bound) 25(OH)D has not been investigated in critical illness. Moreover, the relationship of free 25(OH)D and th...

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Veröffentlicht in:Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2017-06, Vol.38, p.102-108
Hauptverfasser: Han, Jenny E., Alvarez, Jessica A., Jones, Jennifer L., Tangpricha, Vin, Brown, Mona A., Hao, Li, Brown, Lou Ann S., Martin, Greg S., Ziegler, Thomas R.
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container_title Nutrition (Burbank, Los Angeles County, Calif.)
container_volume 38
creator Han, Jenny E.
Alvarez, Jessica A.
Jones, Jennifer L.
Tangpricha, Vin
Brown, Mona A.
Hao, Li
Brown, Lou Ann S.
Martin, Greg S.
Ziegler, Thomas R.
description High-dose vitamin D3 increases plasma total 25-hydroxyvitamin D [25(OH)D] in critically ill, ventilated patients; however, to our knowledge, the effect on plasma levels of free (nonprotein-bound) 25(OH)D has not been investigated in critical illness. Moreover, the relationship of free 25(OH)D and the regulation of endogenous antimicrobial peptides (AMPs) remains unknown. The aims of this study were to determine in critically ill adults with respiratory failure the effect of previous high-dose regimens of vitamin D3 on free 25(OH)D concentrations, the relationship of free 25(OH)D with circulating cathelicidin (LL-37) and human beta-defensin-2 (hBD-2), and the associations between plasma levels of free 25(OH)D and these AMPs to alveolar macrophage phagocytosis function. 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 d) or placebo. Plasma was obtained serially for concentrations of free 25(OH)D, LL-37, hBD-2, and expression of peripheral blood mononuclear cell human cationic antimicrobial protein (hCAP18) mRNA. Total 25(OH)D and LL-37 concentrations and alveolar macrophage phagocytosis were determined in bronchoalveolar lavage fluid. Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P 
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Moreover, the relationship of free 25(OH)D and the regulation of endogenous antimicrobial peptides (AMPs) remains unknown. The aims of this study were to determine in critically ill adults with respiratory failure the effect of previous high-dose regimens of vitamin D3 on free 25(OH)D concentrations, the relationship of free 25(OH)D with circulating cathelicidin (LL-37) and human beta-defensin-2 (hBD-2), and the associations between plasma levels of free 25(OH)D and these AMPs to alveolar macrophage phagocytosis function. 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 d) or placebo. Plasma was obtained serially for concentrations of free 25(OH)D, LL-37, hBD-2, and expression of peripheral blood mononuclear cell human cationic antimicrobial protein (hCAP18) mRNA. Total 25(OH)D and LL-37 concentrations and alveolar macrophage phagocytosis were determined in bronchoalveolar lavage fluid. Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P &lt; 0.001). The increase in free 25(OH)D was greater with the 500 000 IU vitamin D3 dose than with the lower dose. The percent change in mRNA expression of hCAP18 was positively associated with percent change in free 25(OH)D at days 7 and 14 (ρ = 0.48; P = 0.04 and ρ = 0.59; P = 0.03, respectively). Additionally, plasma LL-37 levels correlated with the percentage of alveolar macrophages exhibiting phagocytosis (ρ = 0.51; P = 0.04). The present study 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 25(OH)D against plasma LL-37 and hBD-2 concentrations. Larger studies appear warranted to determine the impact of high-dose vitamin D3 administration on endogenous AMPs. •To our knowledge, this is the first study to determine free vitamin D [25(OH)D] levels in critically ill adult patients.•Plasma free-25(OH)D increased with vitamin D3 treatment in a dose–response manner.•Plasma free-25(OH)D levels correlated with percent change in mRNA expression of human cationic antimicrobial protein.•Plasma total-25(OH)D did not correlate with antimicrobial peptide expression.•Plasma cathelicidin levels significantly correlated with alveolar macrophage phagocytosis.</description><identifier>ISSN: 0899-9007</identifier><identifier>EISSN: 1873-1244</identifier><identifier>DOI: 10.1016/j.nut.2017.02.002</identifier><language>eng</language><publisher>Elsevier Inc</publisher><subject>adults ; Antimicrobial peptides ; antimicrobial proteins ; cathelicidins ; cholecalciferol ; Critical care ; gene expression ; LL-37 ; macrophages ; messenger RNA ; mononuclear leukocytes ; patients ; phagocytosis ; placebos ; Respiratory failure ; Vitamin D</subject><ispartof>Nutrition (Burbank, Los Angeles County, Calif.), 2017-06, Vol.38, p.102-108</ispartof><rights>2017 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0899900717300345$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids></links><search><creatorcontrib>Han, Jenny E.</creatorcontrib><creatorcontrib>Alvarez, Jessica A.</creatorcontrib><creatorcontrib>Jones, Jennifer L.</creatorcontrib><creatorcontrib>Tangpricha, Vin</creatorcontrib><creatorcontrib>Brown, Mona A.</creatorcontrib><creatorcontrib>Hao, Li</creatorcontrib><creatorcontrib>Brown, Lou Ann S.</creatorcontrib><creatorcontrib>Martin, Greg S.</creatorcontrib><creatorcontrib>Ziegler, Thomas R.</creatorcontrib><title>Impact of high-dose vitamin D3 on plasma free 25-hydroxyvitamin D concentrations and antimicrobial peptides in critically ill mechanically ventilated adults</title><title>Nutrition (Burbank, Los Angeles County, Calif.)</title><description>High-dose vitamin D3 increases plasma total 25-hydroxyvitamin D [25(OH)D] in critically ill, ventilated patients; however, to our knowledge, the effect on plasma levels of free (nonprotein-bound) 25(OH)D has not been investigated in critical illness. Moreover, the relationship of free 25(OH)D and the regulation of endogenous antimicrobial peptides (AMPs) remains unknown. The aims of this study were to determine in critically ill adults with respiratory failure the effect of previous high-dose regimens of vitamin D3 on free 25(OH)D concentrations, the relationship of free 25(OH)D with circulating cathelicidin (LL-37) and human beta-defensin-2 (hBD-2), and the associations between plasma levels of free 25(OH)D and these AMPs to alveolar macrophage phagocytosis function. 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 d) or placebo. Plasma was obtained serially for concentrations of free 25(OH)D, LL-37, hBD-2, and expression of peripheral blood mononuclear cell human cationic antimicrobial protein (hCAP18) mRNA. Total 25(OH)D and LL-37 concentrations and alveolar macrophage phagocytosis were determined in bronchoalveolar lavage fluid. Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P &lt; 0.001). The increase in free 25(OH)D was greater with the 500 000 IU vitamin D3 dose than with the lower dose. The percent change in mRNA expression of hCAP18 was positively associated with percent change in free 25(OH)D at days 7 and 14 (ρ = 0.48; P = 0.04 and ρ = 0.59; P = 0.03, respectively). Additionally, plasma LL-37 levels correlated with the percentage of alveolar macrophages exhibiting phagocytosis (ρ = 0.51; P = 0.04). The present study 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 25(OH)D against plasma LL-37 and hBD-2 concentrations. 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Alvarez, Jessica A. ; Jones, Jennifer L. ; Tangpricha, Vin ; Brown, Mona A. ; Hao, Li ; Brown, Lou Ann S. ; Martin, Greg S. ; Ziegler, Thomas R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e188t-3e9578b0ef4d2a086d34d07c575ca38a84b9a9969fc11c0f8e7d0eb0d36d43263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>adults</topic><topic>Antimicrobial peptides</topic><topic>antimicrobial proteins</topic><topic>cathelicidins</topic><topic>cholecalciferol</topic><topic>Critical care</topic><topic>gene expression</topic><topic>LL-37</topic><topic>macrophages</topic><topic>messenger RNA</topic><topic>mononuclear leukocytes</topic><topic>patients</topic><topic>phagocytosis</topic><topic>placebos</topic><topic>Respiratory failure</topic><topic>Vitamin D</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, Jenny E.</creatorcontrib><creatorcontrib>Alvarez, Jessica A.</creatorcontrib><creatorcontrib>Jones, Jennifer L.</creatorcontrib><creatorcontrib>Tangpricha, Vin</creatorcontrib><creatorcontrib>Brown, Mona A.</creatorcontrib><creatorcontrib>Hao, Li</creatorcontrib><creatorcontrib>Brown, Lou Ann S.</creatorcontrib><creatorcontrib>Martin, Greg S.</creatorcontrib><creatorcontrib>Ziegler, Thomas R.</creatorcontrib><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Nutrition (Burbank, Los Angeles County, Calif.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Jenny E.</au><au>Alvarez, Jessica A.</au><au>Jones, Jennifer L.</au><au>Tangpricha, Vin</au><au>Brown, Mona A.</au><au>Hao, Li</au><au>Brown, Lou Ann S.</au><au>Martin, Greg S.</au><au>Ziegler, Thomas R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of high-dose vitamin D3 on plasma free 25-hydroxyvitamin D concentrations and antimicrobial peptides in critically ill mechanically ventilated adults</atitle><jtitle>Nutrition (Burbank, Los Angeles County, Calif.)</jtitle><date>2017-06</date><risdate>2017</risdate><volume>38</volume><spage>102</spage><epage>108</epage><pages>102-108</pages><issn>0899-9007</issn><eissn>1873-1244</eissn><abstract>High-dose vitamin D3 increases plasma total 25-hydroxyvitamin D [25(OH)D] in critically ill, ventilated patients; however, to our knowledge, the effect on plasma levels of free (nonprotein-bound) 25(OH)D has not been investigated in critical illness. Moreover, the relationship of free 25(OH)D and the regulation of endogenous antimicrobial peptides (AMPs) remains unknown. The aims of this study were to determine in critically ill adults with respiratory failure the effect of previous high-dose regimens of vitamin D3 on free 25(OH)D concentrations, the relationship of free 25(OH)D with circulating cathelicidin (LL-37) and human beta-defensin-2 (hBD-2), and the associations between plasma levels of free 25(OH)D and these AMPs to alveolar macrophage phagocytosis function. 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 d) or placebo. Plasma was obtained serially for concentrations of free 25(OH)D, LL-37, hBD-2, and expression of peripheral blood mononuclear cell human cationic antimicrobial protein (hCAP18) mRNA. Total 25(OH)D and LL-37 concentrations and alveolar macrophage phagocytosis were determined in bronchoalveolar lavage fluid. Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P &lt; 0.001). The increase in free 25(OH)D was greater with the 500 000 IU vitamin D3 dose than with the lower dose. The percent change in mRNA expression of hCAP18 was positively associated with percent change in free 25(OH)D at days 7 and 14 (ρ = 0.48; P = 0.04 and ρ = 0.59; P = 0.03, respectively). Additionally, plasma LL-37 levels correlated with the percentage of alveolar macrophages exhibiting phagocytosis (ρ = 0.51; P = 0.04). The present study 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 25(OH)D against plasma LL-37 and hBD-2 concentrations. Larger studies appear warranted to determine the impact of high-dose vitamin D3 administration on endogenous AMPs. •To our knowledge, this is the first study to determine free vitamin D [25(OH)D] levels in critically ill adult patients.•Plasma free-25(OH)D increased with vitamin D3 treatment in a dose–response manner.•Plasma free-25(OH)D levels correlated with percent change in mRNA expression of human cationic antimicrobial protein.•Plasma total-25(OH)D did not correlate with antimicrobial peptide expression.•Plasma cathelicidin levels significantly correlated with alveolar macrophage phagocytosis.</abstract><pub>Elsevier Inc</pub><doi>10.1016/j.nut.2017.02.002</doi><tpages>7</tpages></addata></record>
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identifier ISSN: 0899-9007
ispartof Nutrition (Burbank, Los Angeles County, Calif.), 2017-06, Vol.38, p.102-108
issn 0899-9007
1873-1244
language eng
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source Elsevier ScienceDirect Journals
subjects adults
Antimicrobial peptides
antimicrobial proteins
cathelicidins
cholecalciferol
Critical care
gene expression
LL-37
macrophages
messenger RNA
mononuclear leukocytes
patients
phagocytosis
placebos
Respiratory failure
Vitamin D
title Impact of high-dose vitamin D3 on plasma free 25-hydroxyvitamin D concentrations and antimicrobial peptides in critically ill mechanically ventilated adults
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