Effects of the second-generation synthetic lipid A analogue E5564 on responses to endotoxin in [corrected] equine whole blood and monocytes.
Am J Vet Res
; 69(6): 796-803, 2008 Jun.
Article
en En
| MEDLINE
| ID: mdl-18518661
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)-alpha production; and mRNA expression of TNF-alpha, interleukin (IL)-1beta, 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 O111B4 LPS, E5564, or E5564 plus E coli O111B4 LPS. Whole blood and cell supernatants were assayed for TNF-alpha, and cell lysates were assayed to determine PCA. Expression of mRNA for TNF-alpha, IL-1beta, 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-alpha production in a concentration-dependent manner. Furthermore, E5564 significantly inhibited LPS-induced mRNA expression of TNF-alpha, IL-1beta, 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Lipopolisacáridos
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Caballos
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Lípido A
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Antiinflamatorios
Límite:
Animals
Idioma:
En
Revista:
Am J Vet Res
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos