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气道季节性抗菌活性:一项随机安慰剂对照双盲试验的事后分析。

Seasonal Antimicrobial Activity of the Airway: Post-Hoc Analysis of a Randomized Placebo-Controlled Double-Blind Trial.

机构信息

Department of Internal Medicine, Carver College of Medicine Iowa City, University of Iowa, Iowa City, IA 52242, USA.

Department of Pediatrics, Carver College of Medicine Iowa City, University of Iowa, Iowa City, IA 52242, USA.

出版信息

Nutrients. 2020 Aug 27;12(9):2602. doi: 10.3390/nu12092602.

Abstract

BACKGROUND

It is widely unknown why respiratory infections follow a seasonal pattern. Variations in ultraviolet B (UVB) light during seasons affects cutaneous synthesis of vitamin D. Serum vitamin D concentration influences the expression of airway surface liquid (ASL) antimicrobial peptides such as LL-37.

OBJECTIVE

We sought to determine the effect of seasons on serum vitamin D levels and ASL antimicrobial activity.

METHODS

Forty participants, 18-60 years old, were randomized 1:1 to receive 90 days of 1000 IU vitamin D or placebo. We collected ASL via bronchoscopy and measured serum 25(OH) vitamin D from participants before and after intervention across seasons. We measured ASL antimicrobial activity by challenging samples with bioluminescent and measured relative light units (RLUs) after four minutes. We also investigated the role of LL-37 using a monoclonal neutralizing antibody.

RESULTS

We found that participants, prior to any intervention, during summer-fall ( = 20) compared to winter-spring ( = 20) had (1) decreased live bacteria after challenge (5542 ± 175.2 vs. 6585 ± 279 RLU, = 0.003) and (2) higher serum vitamin D (88.25 ± 24.25 vs. 67.5 ± 45.25 nmol/L, = 0.026). Supplementation with vitamin D increased vitamin D levels and restored ASL antimicrobial activity only during the winter-spring. The increased ASL antimicrobial activity seen during the summer-fall was abrogated by adding the LL-37 neutralizing antibody.

CONCLUSION

ASL kills bacteria more effectively during the summer-fall compared to the winter-spring. Supplementation of vitamin D during winter-spring restores ASL antimicrobial activity by increasing the expression of antimicrobial peptides including LL-37.

摘要

背景

呼吸道感染为何呈季节性模式,目前还鲜为人知。季节变化会影响皮肤合成维生素 D 的紫外线 B(UVB)光。血清维生素 D 浓度会影响气道表面液体(ASL)抗菌肽的表达,如 LL-37。

目的

我们旨在确定季节对血清维生素 D 水平和 ASL 抗菌活性的影响。

方法

40 名 18-60 岁的参与者被随机 1:1 分配接受 90 天的 1000IU 维生素 D 或安慰剂。我们通过支气管镜收集 ASL,并在季节之间测量干预前后参与者的血清 25(OH)维生素 D。我们通过用生物发光法挑战样本来测量 ASL 抗菌活性,并在四分钟后测量相对光单位(RLU)。我们还使用单克隆中和抗体研究了 LL-37 的作用。

结果

我们发现,在任何干预之前,与冬季-春季相比( = 20),夏季-秋季的参与者(1)经挑战后活菌减少(5542 ± 175.2 与 6585 ± 279 RLU, = 0.003),(2)血清维生素 D 水平较高(88.25 ± 24.25 与 67.5 ± 45.25 nmol/L, = 0.026)。仅在冬季-春季补充维生素 D 可增加维生素 D 水平并恢复 ASL 抗菌活性。夏季-秋季观察到的增加的 ASL 抗菌活性在添加 LL-37 中和抗体后被阻断。

结论

与冬季-春季相比,ASL 在夏季-秋季更有效地杀死细菌。在冬季-春季补充维生素 D 通过增加包括 LL-37 在内的抗菌肽的表达来恢复 ASL 抗菌活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6046/7551279/0fb431894bb8/nutrients-12-02602-g001.jpg

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