Czeslick et al. (77) carried out an ex vivo study on the effect of E5564 on production of LPS-induced pro-inflammatory cytokines, particularly IL-6 and TNF-α, in LPS-induced human monocytes. In this study, they recruited 10 healthy volunteers and obtained their whole blood samples and preincubated with 0.001, 0.003, 0.01, 0.03, 0.1, 1 and 10 ng/ml E5564 for 45 min and after stimulated with 0.2 ng/ml of LPS. They found that E5564 (0.003 up to 10 ng/ml) caused a dosedependent inhibitory effect on IL-6 and TNF-α production in LPS-stimulated human monocytes. They concluded that E5564 has a significant LPS inhibitory effect via down regulation of the intracellular generation of pro-inflammatory cytokines IL-6 and TNF-α in human monocytes (77) .