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血细胞吸附体外疗法可在体外去除马体内的细胞因子。

Hemadsorption extracorporeal therapy removes cytokines ex vivo in horses.

作者信息

Hobbs Kallie J, Davis Jennifer L, Cooper Bethanie L, Ueda Yu, Burke Megan J, Sheats M Katie

机构信息

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA.

出版信息

Am J Vet Res. 2024 Mar 18;85(6). doi: 10.2460/ajvr.24.01.0022. Print 2024 Jun 1.

Abstract

OBJECTIVE

Plasma cytokine adsorption has shown benefit as an adjunctive therapy in human sepsis but has yet to be investigated in horses. We hypothesized that ex vivo filtration of equine plasma with a novel cytokine adsorption device would significantly reduce concentrations of lipopolysaccharide-stimulated cytokines. We also hypothesized that the device would adsorb medications commonly used to treat sepsis.

ANIMALS

8 horses owned by North Carolina State University.

METHODS

Four liters of heparinized whole blood was collected from healthy adult horses (n = 8) and stimulated with lipopolysaccharide (100 ng/mL) for 6 hours (37 °C.) from June 4, 2023, to December 15, 2023. Plasma was filtered through a cytokine adsorption device or sham circuit. Samples were collected at 11 time points for multiplex cytokine analysis. Chemistry analysis was performed before and after filtration. To investigate the impact of the device on medication concentrations, equine plasma containing potassium penicillin, gentamicin, and flunixin meglumine was filtered through the cytokine adsorption device or sham for 6 hours. Drug concentrations before and after filtration were determined by ultra-high-performance liquid chromatography. Prefiltration versus postfiltration sample concentrations were analyzed by Student paired t test using GraphPad Prism 9.0 (P < .05).

RESULTS

Filtration of lipopolysaccharide-stimulated equine plasma (n = 8) for 6 hours resulted in significant mean reductions in the cytokines IL-10, IL-5, IL-8, tumor necrosis factor-α (TNF-α), and IL-1β, as well as albumin. Drug concentrations of potassium penicillin, gentamicin, and flunixin meglumine were also significantly reduced by filtration.

CLINICAL RELEVANCE

This work provides proof of concept for further investigation of extracorporeal cytokine adsorption as a potential adjunct treatment for equine sepsis.

摘要

目的

血浆细胞因子吸附已被证明作为人类脓毒症的辅助治疗有益,但尚未在马匹中进行研究。我们假设,使用新型细胞因子吸附装置对马血浆进行体外过滤将显著降低脂多糖刺激的细胞因子浓度。我们还假设该装置会吸附常用于治疗脓毒症的药物。

动物

北卡罗来纳州立大学拥有的8匹马。

方法

从健康成年马(n = 8)采集4升肝素化全血,于2023年6月4日至2023年12月15日用脂多糖(100 ng/mL)刺激6小时(37°C)。血浆通过细胞因子吸附装置或假循环进行过滤。在11个时间点采集样本进行多重细胞因子分析。过滤前后进行化学分析。为了研究该装置对药物浓度的影响,将含有青霉素钾、庆大霉素和氟尼辛葡甲胺的马血浆通过细胞因子吸附装置或假循环过滤6小时。过滤前后的药物浓度通过超高效液相色谱法测定。使用GraphPad Prism 9.0通过学生配对t检验分析过滤前与过滤后样本浓度(P < .05)。

结果

对脂多糖刺激的马血浆(n = 8)过滤6小时导致细胞因子IL-10、IL-5、IL-8、肿瘤坏死因子-α(TNF-α)和IL-1β以及白蛋白的平均浓度显著降低。青霉素钾、庆大霉素和氟尼辛葡甲胺的药物浓度也因过滤而显著降低。

临床意义

这项工作为进一步研究体外细胞因子吸附作为马脓毒症潜在辅助治疗提供了概念验证。

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