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


METHODS
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.
Czeslick
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E
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
Struppert
A
A
Simm
A
A
Sablotzki
A
A
D000328:Adult; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
C404742:E5564; D015850:Interleukin-6; D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha