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)-α 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°C and 5% CO2. Intracellular expression of IL-6 and TNF-α 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-α 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-α in human monocytes.
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Received 8 April 2006; returned for revision 13 June 2006; accepted by G. Wallace 7 July 2006
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Czeslick, E., Struppert, A., Simm, A. et al. E5564 (Eritoran) inhibits lipopolysaccharide-induced cytokine production in human blood monocytes. Inflamm. res. 55, 511–515 (2006). https://doi.org/10.1007/s00011-006-6057-3
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DOI: https://doi.org/10.1007/s00011-006-6057-3