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
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Emory University, Atlanta, Georgia, USA; Emory Critical Care Center, Emory University, Atlanta, Georgia, USA.
Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, Georgia, USA.
Nutrition. 2017 Jun;38:102-108. doi: 10.1016/j.nut.2017.02.002. Epub 2017 Feb 27.
High-dose vitamin D 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 D 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 D (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 < 0.001). The increase in free 25(OH)D was greater with the 500 000 IU vitamin D 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 D administration on endogenous AMPs.
高剂量维生素D可提高危重症机械通气患者血浆总25-羟基维生素D[25(OH)D]水平；然而，据我们所知，尚未研究其对危重症患者血浆游离（非蛋白结合）25(OH)D水平的影响。此外，游离25(OH)D与内源性抗菌肽(AMP)调节之间的关系仍不清楚。本研究的目的是确定在患有呼吸衰竭的危重症成年患者中，既往高剂量维生素D方案对游离25(OH)D浓度的影响、游离25(OH)D与循环中的cathelicidin(LL-37)和人β-防御素-2(hBD-2)的关系，以及游离25(OH)D血浆水平与这些AMP对肺泡巨噬细胞吞噬功能的关联。
在一项双盲、随机对照试验中，依赖机械通气的危重症成年患者（N = 30）接受肠内维生素D（5天内总量250,000或500,000 IU）或安慰剂。连续采集血浆以检测游离25(OH)D、LL-37、hBD-2的浓度以及外周血单核细胞人阳离子抗菌蛋白(hCAP18)mRNA的表达。测定支气管肺泡灌洗液中的总25(OH)D和LL-37浓度以及肺泡巨噬细胞吞噬功能。
血浆游离25(OH)D浓度随时间的变化与总25(OH)D水平相关(r = 0.82; P < 0.001)。维生素D剂量为500 000 IU时游离25(OH)D的增加幅度大于较低剂量时。在第7天和第14天，hCAP18 mRNA表达的百分比变化与游离25(OH)D的百分比变化呈正相关(分别为ρ = 0.48; P = 0.04和ρ = 0.59; P = 0.03)。此外，血浆LL-37水平与表现出吞噬作用的肺泡巨噬细胞百分比相关(ρ = 0.51; P = 0.04)。
本研究发现血浆游离25(OH)D水平呈剂量相关增加，且随时间推移与循环中hCAP18 mRNA表达增加相关。总25(OH)D和游离25(OH)D的变化与血浆LL-37和hBD-2浓度之间无相关性。似乎需要进行更大规模的研究来确定高剂量维生素D给药对内源性AMP的影响。
