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

IF 2.2 2区农林科学 Q1 VETERINARY SCIENCES

Journal of Veterinary Internal Medicine Pub Date : 2025-09-09 DOI:10.1111/jvim.70240

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

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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-D₃ (25(OH)D₃) concentrations ≤ 30 ng/mL.

Methods

Prospective, randomized, double-blinded, placebo-controlled crossover study. Dogs were randomized to receive calcifediol at 2.3 μg/kg^0.75 (low-dose), 4.6 μg/kg^0.75 (high-dose), or placebo for 7 days and crossed over to a different treatment arm after 28-day washout periods. Serum 25(OH)D₃ 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)D₃ 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)D₃ 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.

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短期补充钙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

维生素D可以调节包括狗在内的许多物种的免疫反应。迄今为止，有关维生素D对狗的免疫作用的研究仅限于体外研究。目的向健康犬补充PO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。11只健康犬，血清25-羟基维生素D3 （25(OH)D3）浓度≤30 ng/mL。方法前瞻性、随机、双盲、安慰剂对照交叉研究。狗随机接受2.3 μg/kg0.75（低剂量）、4.6 μg/kg0.75（高剂量）或安慰剂治疗7天，并在28天的洗脱期后转入不同的治疗组。采用改进的高效液相色谱法测定血清25(OH)D3。全血培养采用脂多糖（LPS）、脂质胆酸（LTA）或磷酸盐缓冲盐水（PBS）孵育24小时，上清采用犬类特异性多重测定法测定TNF-α、IL-6和IL-10。结果低剂量（中位数，四分位数范围[IQR]； 62 ng/mL, 59-82）和高剂量（93 ng/mL, 80-113） PO钙化二醇补充均使血清25(OH)D3浓度较基线升高（22.2 ng/mL, 20.3-29.3, p < 0.0001）。低剂量和高剂量钙化二醇补充分别降低了lps刺激的IL-6 197 pg/mL（95%可信区间[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)D3浓度每增加1 ng/mL， lps刺激下IL-6浓度降低2 pg/mL （95% CI:−3.0 ~−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，可降低lps刺激下的IL-6浓度。口服钙化二醇补充剂可能对狗有抗炎作用。

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来源期刊

Journal of Veterinary Internal Medicine 农林科学-兽医学

CiteScore

4.50

自引率

11.50%

发文量

243

审稿时长

22 weeks

期刊介绍： The mission of the Journal of Veterinary Internal Medicine is to advance veterinary medical knowledge and improve the lives of animals by publication of authoritative scientific articles of animal diseases.