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Inflamm Res. 2006 Nov;55(11):511-5.

E5564 (Eritoran) inhibits lipopolysaccharide-induced cytokine production in human blood monocytes.

Author information

1
Department of Anesthesiology and Critical Care Medicine, Martin Luther University Halle, Ernst-Grube-Str. 40, 06120, Halle/Saale, Germany. elke.czeslick@medizin.uni-halle.de

Abstract

OBJECTIVE AND DESIGN:

In this ex vivo laboratory study, we investigated the effects of E5564 (eritoran), a toll-like receptor 4-directed endotoxin antagonist, on intracellular expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in lipopolysaccharide (LPS)-stimulated human monocytes assessed by flow cytometry.

MATERIAL AND METHOD:

Whole blood samples from 10 healthy volunteers (average age: 32 +/- 2 years) were pre-incubated with 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1 and 10 ng/ml E5564 for 45 min and after this stimulated with LPS (0.2 ng/ml), a dose we found to be the most effective for stimulation. Samples were incubated for 3 h at 37 degrees C and 5% CO(2). Intracellular expression of IL-6 and TNF-alpha was assessed by flow cytometry.

RESULTS:

Our investigation showed that E5564 (0.03 ng/ml up to 10 ng/ml) caused a dose-dependent inhibitory effect on IL-6 and TNF-alpha production in LPS-stimulated human monocytes.

CONCLUSIONS:

The results of this investigation led us to conclude that E5564 has a remarkable LPS inhibitory activity manifested via down-regulation of the intracellular generation of pro-inflammatory cytokines IL-6 and TNF-alpha in human monocytes.

PMID:
17122970
DOI:
10.1007/s00011-006-6057-3
[Indexed for MEDLINE]
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