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）。