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Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses

Elizabeth M. Tadros DVM, PhD1 and Nicholas Frank DVM, PhD2
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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.

Abstract

Objective—To determine whether the method of lipopolysaccharide (LPS) administration (intermittent vs continuous) affects the magnitude and duration of the systemic inflammatory response in horses and whether prolonged (48 hours) endotoxemia induces laminitis.

Animals—12 healthy adult horses (10 mares and 2 geldings).

Procedures—Horses were randomly assigned to receive LPS (total dose, 80 μg; n = 4) or saline (0.9% NaCl) solution (80 mL/h; 4) via constant rate infusion or 8 bolus IV injections of LPS (10 μg, q 6 h;4) during a 48-hour period. Physical examinations were performed every 4 hours, inflammatory cytokine gene expression was determined for blood samples obtained every 8 hours, and IV glucose tolerance tests were performed.

Results—All LPS-treated horses had signs of depression and mild colic; those signs abated as the study progressed. Administration of LPS increased expression of interleukin-1β, interleukin-6, and interleukin-8, but results were not significantly different between LPS treatment groups. Cytokine expression was significantly higher on the first day versus the second day of LPS treatment. Interleukin-1β expression was positively correlated with rectal temperature and expression of other cytokines. Glucose and insulin dynamics for both LPS groups combined did not differ significantly from those of the saline solution group. Signs of laminitis were not detected in any of the horses.

Conclusions and Clinical Relevance—Horses developed LPS tolerance within approximately 24 hours after administration was started, and the method of LPS administration did not affect the magnitude or duration of systemic inflammation. Laminitis was not induced in horses.

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 Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

Supported by the University of Tennessee College of Veterinary Medicine Center of Excellence, the Charles and Julie Wharton Fellowship, and the Wells Graduate Student Fellowship.

Presented as a poster presentation at the American College of Veterinary Internal Medicine Forum, Anaheim, Calif, June 2010.

The authors thank Dr. David Horohov for technical assistance with the real-time PCR assay techniques and for providing primer sequences and Dr. Arnold Saxton for assistance with the statistical analysis.

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