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American journal of veterinary research2024; 85(6); doi: 10.2460/ajvr.24.01.0022

Hemadsorption extracorporeal therapy removes cytokines ex vivo in horses.

Abstract: 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. Methods: 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. Conclusions: This work provides proof of concept for further investigation of extracorporeal cytokine adsorption as a potential adjunct treatment for equine sepsis.
Publication Date: 2024-03-18 PubMed ID: 38484466DOI: 10.2460/ajvr.24.01.0022Google Scholar: Lookup
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  • Journal Article

Summary

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The research explores the effectiveness of an extracorporeal therapy device in reducing cytokine concentration in stimulated horse plasma, potentially evidencing a new treatment method for horse sepsis.

Objective of the Research

  • The study sought to investigate whether a cytokine adsorption device would effectively lower the levels of inflammatory markers, known as cytokines, in the plasma of horses. Cytokines are released into the bloodstream as part of the body’s immune response, especially during sepsis.

Methodology

  • Whole blood was collected from 8 healthy adult horses, stimulated with a specific dose of lipopolysaccharide—a compound known to prompt an immune reaction—and analyzed for cytokine concentrations.
  • The stimulated blood plasma was then filtered through this novel cytokine adsorption device.
  • At 11 different time points, samples were collected for a multiplex cytokine analysis.
  • For examining whether the device would also adsorb common sepsis medications, equine plasma containing certain drugs was filtered through the same device.
  • The drug concentrations were measured pre-and post-filtration.

Results

  • The filtration of the stimulated equine plasma experienced significant mean reductions in several types of cytokines, including IL-10, IL-5, IL-8, TNF-α, and IL-1β.
  • Similarly, the concentrations of medications—including potassium penicillin, gentamicin, and flunixin meglumine—used in the treatment of horse sepsis, were also significantly decreased after filtration.

Conclusions

  • This study serves as an initial substantiation for the application of the extracorporeal cytokine adsorption method as a supportive treatment for horse sepsis.
  • The cytokine adsorption device might help manage sepsis by lowering the inflammation-causing cytokines in the plasma of horses. However, the reduction in medication concentration indicates that further research is necessary to understand this effect and its implications.

Cite This Article

APA
Hobbs KJ, Davis JL, Cooper BL, Ueda Y, Burke MJ, Sheats MK. (2024). Hemadsorption extracorporeal therapy removes cytokines ex vivo in horses. Am J Vet Res, 85(6). https://doi.org/10.2460/ajvr.24.01.0022

Publication

ISSN: 1943-5681
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 85
Issue: 6

Researcher Affiliations

Hobbs, Kallie J
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.
Davis, Jennifer L
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA.
Cooper, Bethanie L
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.
Ueda, Yu
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.
Burke, Megan J
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.
Sheats, M Katie
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

MeSH Terms

  • Animals
  • Horses
  • Cytokines / metabolism
  • Cytokines / blood
  • Lipopolysaccharides
  • Horse Diseases / therapy
  • Sepsis / veterinary
  • Sepsis / therapy
  • Adsorption
  • Male
  • Female
  • Anti-Bacterial Agents