Human peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood obtained from healthy human volunteers by density gradient centrifugation (68) . TAK-242 was effective in human cells and inhibited the production of TNF-α, IL-6, and IL-1b from PBMCs stimulated with LPS and IFN-gamma, with IC 50 values of TAK-242 ranging from 5.3 to 58 nM. There were four donors used for this study. There was no marked difference in the IC 50 values of TAK-242 amongst them. TAK-242 showed suppressive effects on the production of various inflammatory mediators from human monocytes and macrophages stimulated with LPS. TAK-242 also suppressed the production of these cytokines from LPS-stimulated human peripheral blood mononuclear cells (PBMCs) at IC 50 values from 11 to 33 nM. In addition, the inhibitory effects on the LPS-induced IL-6 and IL-12 production were similar in human PBMCs, monocytes, and macrophages. TAK-242 suppressed the cytokine production induced by Toll-like receptor (TLR) 4 ligands, but not by ligands for TLR2, TLR3, and TLR9. TAK-242 suppresses the production of multiple cytokines by selectively inhibiting TLR4 intracellular signaling (68) .