Jared A. Jaffey, Rachael Kreisler, Robert C. Backus, Danielle Gordon, Lauren Chittick
{"title":"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","authors":"Jared A. Jaffey, Rachael Kreisler, Robert C. Backus, Danielle Gordon, Lauren Chittick","doi":"10.1111/jvim.70240","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Objectives</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Animals</h3>\n \n <p>Eleven healthy client-owned dogs with serum 25-hydroxyvitamin-D<sub>3</sub> (25(OH)D<sub>3</sub>) concentrations ≤ 30 ng/mL.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Prospective, randomized, double-blinded, placebo-controlled crossover study. Dogs were randomized to receive calcifediol at 2.3 μg/kg<sup>0.75</sup> (low-dose), 4.6 μg/kg<sup>0.75</sup> (high-dose), or placebo for 7 days and crossed over to a different treatment arm after 28-day washout periods. Serum 25(OH)D<sub>3</sub> 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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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<sub>3</sub> concentrations from baseline (22.2 ng/mL, 20.3–29.3; both <i>p</i> < 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; <i>p</i> = 0.03) and 182 pg/mL (95% CI: −355.0 to −8.0; <i>p</i> = 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<sub>3</sub> concentration (95% CI: −3.0 to −0.1; <i>p</i> = 0.03).</p>\n </section>\n \n <section>\n \n <h3> Conclusion and Clinical Importance</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":49958,"journal":{"name":"Journal of Veterinary Internal Medicine","volume":"39 5","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.70240","citationCount":"0","resultStr":"{\"title\":\"Effects of Short-Term Calcifediol Supplementation on Leukocyte Cytokine Production in Healthy Dogs: A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial\",\"authors\":\"Jared A. Jaffey, Rachael Kreisler, Robert C. Backus, Danielle Gordon, Lauren Chittick\",\"doi\":\"10.1111/jvim.70240\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Animals</h3>\\n \\n <p>Eleven healthy client-owned dogs with serum 25-hydroxyvitamin-D<sub>3</sub> (25(OH)D<sub>3</sub>) concentrations ≤ 30 ng/mL.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Prospective, randomized, double-blinded, placebo-controlled crossover study. Dogs were randomized to receive calcifediol at 2.3 μg/kg<sup>0.75</sup> (low-dose), 4.6 μg/kg<sup>0.75</sup> (high-dose), or placebo for 7 days and crossed over to a different treatment arm after 28-day washout periods. Serum 25(OH)D<sub>3</sub> 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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<sub>3</sub> concentrations from baseline (22.2 ng/mL, 20.3–29.3; both <i>p</i> < 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; <i>p</i> = 0.03) and 182 pg/mL (95% CI: −355.0 to −8.0; <i>p</i> = 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<sub>3</sub> concentration (95% CI: −3.0 to −0.1; <i>p</i> = 0.03).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion and Clinical Importance</h3>\\n \\n <p>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.</p>\\n </section>\\n </div>\",\"PeriodicalId\":49958,\"journal\":{\"name\":\"Journal of Veterinary Internal Medicine\",\"volume\":\"39 5\",\"pages\":\"\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-09-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.70240\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Veterinary Internal Medicine\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/jvim.70240\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Veterinary Internal Medicine","FirstCategoryId":"97","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jvim.70240","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
Effects of Short-Term Calcifediol Supplementation on Leukocyte Cytokine Production in Healthy Dogs: A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial
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.
Prospective, randomized, double-blinded, placebo-controlled crossover study. Dogs were randomized to receive calcifediol at 2.3 μg/kg0.75 (low-dose), 4.6 μg/kg0.75 (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.
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.
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