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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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

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Cohort Effect
Lipid A
endotoxins
tumor necrosis factors
Endotoxins
monocytes
lipopolysaccharides
Horses
Monocytes
Lipopolysaccharides
horses
Tumor Necrosis Factor-alpha
blood
interleukin-1
interleukin-10
interleukin-6
Interleukin-1
Interleukin-10
Interleukin-6
production economics

All Science Journal Classification (ASJC) codes

  • veterinary(all)

Cite this

Effects of the second-generation synthetic lipid A analogue E5564 on responses to endotoxin equine whole blood and monocytes. / Figueiredo, Monica D.; Moore, James N.; Vandenplas, Michel L.; Sun, Wan Chun; Murray, Thomas F.

In: American Journal of Veterinary Research, Vol. 69, No. 6, 06.2008, p. 796-803.

Research output: Contribution to journalArticle

Figueiredo, Monica D. ; Moore, James N. ; Vandenplas, Michel L. ; Sun, Wan Chun ; Murray, Thomas F. / Effects of the second-generation synthetic lipid A analogue E5564 on responses to endotoxin equine whole blood and monocytes. In: American Journal of Veterinary Research. 2008 ; Vol. 69, No. 6. pp. 796-803.
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