Jenny E Han1, Jessica A Alvarez2, Jennifer L Jones2, Vin Tangpricha3, Mona A Brown4, Li Hao2, Lou Ann S Brown5, Greg S Martin6, Thomas R Ziegler3. 1. Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Emory University, Atlanta, Georgia, USA; Emory Critical Care Center, Emory University, Atlanta, Georgia, USA. Electronic address: Jehan2@emory.edu. 2. Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, Georgia, USA. 3. Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, Georgia, USA; Atlanta VA Medical Center, Decatur, Georgia, USA. 4. Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Emory University, Atlanta, Georgia, USA. 5. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University, Atlanta, Georgia, USA. 6. Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Emory University, Atlanta, Georgia, USA; Emory Critical Care Center, Emory University, Atlanta, Georgia, USA.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS:Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P < 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). CONCLUSIONS: 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.
RCT Entities:
OBJECTIVES: 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 humanbeta-defensin-2 (hBD-2), and the associations between plasma levels of free 25(OH)D and these AMPs to alveolar macrophage phagocytosis function. METHODS: 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. RESULTS: Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P < 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). CONCLUSIONS: 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.
Authors: V Tangpricha; A Kelly; A Stephenson; K Maguiness; J Enders; K A Robinson; B C Marshall; D Borowitz Journal: J Clin Endocrinol Metab Date: 2012-03-07 Impact factor: 5.958
Authors: G De Pascale; M S Vallecoccia; A Schiattarella; V Di Gravio; S L Cutuli; G Bello; L Montini; M A Pennisi; T Spanu; C Zuppi; S A Quraishi; M Antonelli Journal: Clin Microbiol Infect Date: 2015-12-23 Impact factor: 8.067
Authors: Min Wan; Anne M van der Does; Xiao Tang; Lennart Lindbom; Birgitta Agerberth; Jesper Z Haeggström Journal: J Leukoc Biol Date: 2014-02-18 Impact factor: 4.962
Authors: Tero I Ala-Kokko; Shivaprakash J Mutt; Sara Nisula; Juha Koskenkari; Janne Liisanantti; Pasi Ohtonen; Meri Poukkanen; Jouko J Laurila; Ville Pettilä; Karl-Heinz Herzig Journal: Ann Med Date: 2016-01-22 Impact factor: 4.709
Authors: Malte Book; QiXing Chen; Lutz E Lehmann; Sven Klaschik; Stefan Weber; Jens-Christian Schewe; Markus Luepertz; Andreas Hoeft; Frank Stuber Journal: Crit Care Date: 2007 Impact factor: 9.097
Authors: Jordan A Kempker; Kathryn G West; Russell R Kempker; Oranan Siwamogsatham; Jessica A Alvarez; Vin Tangpricha; Thomas R Ziegler; Greg S Martin Journal: PLoS One Date: 2015-04-07 Impact factor: 3.240
Authors: Paula E Beaumont; Brian McHugh; Emily Gwyer Findlay; Annie Mackellar; Karen J Mackenzie; Richard L Gallo; John R W Govan; A John Simpson; Donald J Davidson Journal: PLoS One Date: 2014-06-02 Impact factor: 3.240
Authors: Marni E Shoemaker; Linda M Huynh; Cory M Smith; Vikkie A Mustad; Maria O Duarte; Joel T Cramer Journal: Top Clin Nutr Date: 2022-06-22 Impact factor: 0.441
Authors: Agnieszka Rusińska; Paweł Płudowski; Mieczysław Walczak; Maria K Borszewska-Kornacka; Artur Bossowski; Danuta Chlebna-Sokół; Justyna Czech-Kowalska; Anna Dobrzańska; Edward Franek; Ewa Helwich; Teresa Jackowska; Maria A Kalina; Jerzy Konstantynowicz; Janusz Książyk; Andrzej Lewiński; Jacek Łukaszkiewicz; Ewa Marcinowska-Suchowierska; Artur Mazur; Izabela Michałus; Jarosław Peregud-Pogorzelski; Hanna Romanowska; Marek Ruchała; Piotr Socha; Mieczysław Szalecki; Mirosław Wielgoś; Danuta Zwolińska; Arkadiusz Zygmunt Journal: Front Endocrinol (Lausanne) Date: 2018-05-31 Impact factor: 5.555
Authors: Mohamed Said Boulkrane; Julia Fedotova; Valentina Kolodyaznaya; Vincenzo Micale; Filippo Drago; Annemieke Johanna Maria van den Tol; Denis Baranenko Journal: Curr Neuropharmacol Date: 2020 Impact factor: 7.363
Authors: Robert M Burkes; Jacquie Astemborski; Allison A Lambert; Todd T Brown; Robert A Wise; Gregory D Kirk; M Bradley Drummond Journal: PLoS One Date: 2019-02-27 Impact factor: 3.752
Authors: Karin Amrein; Dhruv Parekh; Sabine Westphal; Jean-Charles Preiser; Andrea Berghold; Regina Riedl; Philipp Eller; Peter Schellongowski; David Thickett; Patrick Meybohm Journal: BMJ Open Date: 2019-11-12 Impact factor: 2.692
Authors: Emily C Sanders; Robert M Burkes; Jason R Mock; Todd T Brown; Robert A Wise; Nadia N Hansel; Mark C Liu; M Bradley Drummond Journal: Chronic Obstr Pulm Dis Date: 2021-07-28
Authors: Albert Shieh; Christina Ma; Rene F Chun; Jonas Wittwer-Schegg; Leon Swinkels; Tonnie Huijs; Jeffrey Wang; Ines Donangelo; Martin Hewison; John S Adams Journal: J Clin Endocrinol Metab Date: 2018-09-01 Impact factor: 6.134