Effects of the second-generation synthetic lipid A analogue E5564 on responses to endotoxin equine whole blood and monocytes

Monica D. Figueiredo, James N. Moore, Michel L. Vandenplas, Wan Chun Sun, Thomas F. Murray

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Abstract

Objective - To evaluate proinflammatory effects of the second-generation synthetic lipid A analogue E5564 on equine whole blood and isolated monocytes and to determine the ability of E5564 to prevent LPS (lipopolysaccharide) - induced procoagulant activity (PCA); tumor necrosis factor (TNF)-α production; and mRNA expression of TNF-α, interleukin (IL)-1β, IL-6, and IL-10 by equine monocytes. Sample Population: - Venous blood samples obtained from 19 healthy horses. Procedures - Whole blood and monocytes were incubated with Escherichia coli O111:B4 LPS, E5564, or E5564 plus E coli O111:B4 LPS. Whole blood and cell supernatants were assayed for TNF-α, and cell lysates were assayed to determine PCA. Expression of mRNA for TNF-α, IL-1β, IL-6, and IL-10 by monocytes was determined by use of real-time quantitative PCR assay. Results - Minimal proinflammatory effects were detected in whole blood and monocytes. In addition, E5564 inhibited LPS-induced PCA and TNF-α production in a concentration-dependent manner. Furthermore, E5564 significantly inhibited LPS-induced mRNA expression of TNF-α, IL-1β, and IL-10 and decreased LPS-induced expression of IL-6. Conclusions and Clinical Relevance - The second-generation synthetic lipid A analogue E5564 lacked agonist activity in equine whole blood and monocytes and was a potent antagonist of enteric LPS. Therefore, E5564 appeared to be the first lipid A analogue that has potential as an effective therapeutic agent in horses with endotoxemia.

Original languageEnglish (US)
Pages (from-to)796-803
Number of pages8
JournalAmerican Journal of Veterinary Research
Volume69
Issue number6
DOIs
StatePublished - Jun 1 2008

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All Science Journal Classification (ASJC) codes

  • veterinary(all)

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