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Effects of equine metabolic syndrome on inflammatory responses of horses to intravenous lipopolysaccharide infusion

Elizabeth M. Tadros DVM, PhD1, Nicholas Frank DVM, PhD2, and Robert L. Donnell DVM, PhD3
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  • 1 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 2 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 3 Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

Abstract

Objective—To test the hypothesis that inflammatory responses to endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS).

Animals—6 healthy horses and 6 horses with EMS.

Procedures—Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline data were obtained 30 minutes before each infusion. After infusion, a physical examination was performed hourly for 9 hours and at 15 and 21 hours; a whole blood sample was collected at 30, 60, 90, 120, 180, and 240 minutes for assessment of inflammatory cytokine gene expression. Liver biopsy was performed between 240 and 360 minutes after infusion.

Results—Following lipopolysaccharide infusion in healthy horses and horses with EMS, mean rectal temperature, heart rate, and respiratory rate increased, compared with baseline findings, as did whole blood gene expression of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α. The magnitude of blood cytokine responses did not differ between groups, but increased expression of IL-6, IL-8, IL-10, and tumor necrosis factor-α persisted for longer periods in EMS-affected horses. Lipopolysaccharide infusion increased liver tissue gene expressions of IL-6 in healthy horses and IL-8 in both healthy and EMS-affected horses, but these gene expressions did not differ between groups.

Conclusions and Clinical Relevance—Results supported the hypothesis that EMS affects horses’ inflammatory responses to endotoxin by prolonging cytokine expression in circulating leukocytes. These findings are relevant to the association between obesity and laminitis in horses with EMS.

Contributor Notes

Dr. Tadros’ present address is Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Dr. Frank's present address is the Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

Supported by the University of Tennessee Center of Excellence in Livestock Diseases and Human Health, the Charles and Julie Wharton Fellowship, and the Wells Graduate Student Fellowship.

Presented in part at the American College of Veterinary Internal Medicine Forum, Denver, June 2011.

The authors thank Dr. David Horohov for providing PCR primer sequences and use of laboratory facilities, Dr. Arnold Saxton for statistical advice, and Sarah Elliott for technical assistance.

Address correspondence to Dr. Frank (nicholas.frank@tufts.edu).