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短期补充骨化二醇对健康犬白细胞细胞因子产生的影响:一项随机、双盲、安慰剂对照交叉试验

Effects of Short-Term Calcifediol Supplementation on Leukocyte Cytokine Production in Healthy Dogs: A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial.

作者信息

Jaffey Jared A, Kreisler Rachael, Backus Robert C, Gordon Danielle, Chittick Lauren

机构信息

Department of Specialty Medicine, Midwestern University College of Veterinary Medicine, Glendale, Arizona, USA.

Department of Pathology and Population Medicine, Midwestern University College of Veterinary Medicine, Glendale, Arizona, USA.

出版信息

J Vet Intern Med. 2025 Sep-Oct;39(5):e70240. doi: 10.1111/jvim.70240.

DOI:10.1111/jvim.70240
PMID:40923554
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12418335/
Abstract

BACKGROUND

Vitamin D modulates the immune response in many species, including dogs. To date, research investigating the immunological effects of vitamin D in dogs is limited to in vitro studies.

OBJECTIVES

Provide PO calcifediol supplementation to healthy dogs to evaluate its tolerability and assess its effect on leukocyte production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10.

ANIMALS

Eleven healthy client-owned dogs with serum 25-hydroxyvitamin-D (25(OH)D) concentrations ≤ 30 ng/mL.

METHODS

Prospective, randomized, double-blinded, placebo-controlled crossover study. Dogs were randomized to receive calcifediol at 2.3 μg/kg (low-dose), 4.6 μg/kg (high-dose), or placebo for 7 days and crossed over to a different treatment arm after 28-day washout periods. Serum 25(OH)D was measured using a modified high-performance liquid chromatography method. Whole blood cultures were performed by incubating blood with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or phosphate-buffered saline (PBS) for 24 h, and TNF-α, IL-6, and IL-10 were measured in supernatant using a canine-specific multiplex assay.

RESULTS

Both low-dose (median, interquartile range [IQR]; 62 ng/mL, 59-82) and high-dose (93 ng/mL, 80-113) PO calcifediol supplementation increased serum 25(OH)D concentrations from baseline (22.2 ng/mL, 20.3-29.3; both p < 0.0001). Low-dose and high-dose calcifediol supplementation decreased LPS-stimulated IL-6 by 197 pg/mL (95% confidence interval [CI]: -369.0 to -24.0; p = 0.03) and 182 pg/mL (95% CI: -355.0 to -8.0; p = 0.04), respectively. Then LPS-stimulated IL-6 concentrations decreased by 2 pg/mL for every 1 ng/mL increase in serum 25(OH)D concentration (95% CI: -3.0 to -0.1; p = 0.03).

CONCLUSION AND CLINICAL IMPORTANCE

Calcifediol supplementation for 7 days was well-tolerated and decreased LPS-stimulated IL-6 concentrations. Oral calcifediol supplementation may have anti-inflammatory effects in dogs.

摘要

背景

维生素D可调节包括犬类在内的许多物种的免疫反应。迄今为止,关于维生素D对犬类免疫作用的研究仅限于体外研究。

目的

对健康犬口服钙化二醇,评估其耐受性,并评估其对肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6和IL-10白细胞生成的影响。

动物

11只血清25-羟基维生素D(25(OH)D)浓度≤30 ng/mL的健康客户拥有的犬。

方法

前瞻性、随机、双盲、安慰剂对照交叉研究。犬被随机分为接受2.3μg/kg(低剂量)、4.6μg/kg(高剂量)的钙化二醇或安慰剂,为期7天,并在28天的洗脱期后交叉至不同的治疗组。采用改良的高效液相色谱法测定血清25(OH)D。通过将血液与脂多糖(LPS)、脂磷壁酸(LTA)或磷酸盐缓冲盐水(PBS)孵育24小时进行全血培养,并使用犬特异性多重检测法测定上清液中的TNF-α、IL-6和IL-10。

结果

低剂量(中位数,四分位间距[IQR];62 ng/mL,59 - 82)和高剂量(93 ng/mL,80 - 113)口服钙化二醇均使血清25(OH)D浓度从基线水平(22.2 ng/mL,20.3 - 29.3)升高(p均<0.0001)。低剂量和高剂量钙化二醇补充剂分别使LPS刺激的IL-6降低197 pg/mL(95%置信区间[CI]:-369.0至-24.0;p = 0.03)和182 pg/mL(95% CI:-355.0至-8.0;p = 0.04)。血清25(OH)D浓度每升高1 ng/mL,LPS刺激的IL-6浓度降低2 pg/mL(95% CI:-3.0至-0.1;p = 0.03)。

结论及临床意义

补充钙化二醇7天耐受性良好,并降低了LPS刺激的IL-6浓度。口服钙化二醇补充剂可能对犬具有抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/149cd1e28012/JVIM-39-e70240-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/4dc3b26132a6/JVIM-39-e70240-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/056cb45a5ca3/JVIM-39-e70240-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/6db8394e3f53/JVIM-39-e70240-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/4ac5735eb8af/JVIM-39-e70240-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/149cd1e28012/JVIM-39-e70240-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/4dc3b26132a6/JVIM-39-e70240-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/056cb45a5ca3/JVIM-39-e70240-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/6db8394e3f53/JVIM-39-e70240-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/4ac5735eb8af/JVIM-39-e70240-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469a/12418335/149cd1e28012/JVIM-39-e70240-g004.jpg

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本文引用的文献

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Vet Sci. 2024 Apr 28;11(5):193. doi: 10.3390/vetsci11050193.
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Age-dependent changes in plasma concentrations of 25-hydroxyvitamin D may complicate vitamin D status assessment of immature cats.25-羟基维生素D血浆浓度的年龄依赖性变化可能会使未成熟猫的维生素D状态评估复杂化。
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Inflammation and Behavior Changes in Dogs and Cats.
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Serum 25(OH)D Concentration, Vitamin D Supplementation, and Risk of Cardiovascular Disease and Mortality in Patients with Type 2 Diabetes or Prediabetes: a Systematic Review and Dose-Response Meta-Analysis.血清 25(OH)D 浓度、维生素 D 补充剂与 2 型糖尿病或糖尿病前期患者心血管疾病和死亡风险:系统评价和剂量反应荟萃分析。
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Effects on Serum Inflammatory Cytokines of Cholecalciferol Supplementation in Healthy Subjects with Vitamin D Deficiency.维生素 D 缺乏健康受试者补充胆钙化醇对血清炎症细胞因子的影响。
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A Single Vitamin D Bolus Supplementation Improves Vitamin D Status and Reduces Proinflammatory Cytokines in Healthy Females.单次维生素 D 冲击疗法补充可改善健康女性的维生素 D 状态并降低促炎细胞因子水平。
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Rapid improvement in vitamin D status with dietary 25-hydroxycholecalciferol in vitamin D insufficient dogs.维生素D不足的犬类通过饮食补充25-羟基胆钙化醇后维生素D状态迅速改善。
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