Edelfosine is taken up by macrophages and inhibits macrophage-derived inflammatory mediators.

(A) Incorporation of edelfosine (EDLF) in mouse bone marrow-derived macrophages (BMM) and mouse RAW 309 Cr.1 tumor macrophage cell line. 106 cells were incubated with 10 μM edelfosine (containing 0.05 μCi [3H]edelfosine) for the indicated times to measure drug uptake. (B) Edelfosine is cytotoxic for transformed macrophages but spares BMM. 2 x 106 cells were incubated for 24 h in the absence or presence of the indicated concentrations of edelfosine (EDLF), and cytotoxicity was determined by the WST-1 reduction method. (C) Edelfosine inhibits superoxide anion generation in BMM. Superoxide anion was measured as lucigenin-dependent chemiluminescence (relative light units, RLU) in untreated control (C) or edelfosine (EDLF)-treated BMM that were incubated with medium alone or zymosan to induce the respiratory burst. (D-F) BMM from edelfosine-fed mice show a decreased generation of inflammatory mediators. BMM from untreated control mice (C) and from mice given orally edelfosine (EDLF) for two weeks were analyzed for their capacity to generate zymosan-induced superoxide anion (D), LPS-induced nitric oxide (E), and IL-12+IL-18-induced IFN-γ (F). Cells incubated with medium alone were run in parallel as a negative control of each assay. Data shown are means ± SD of five independent determinations. Asterisks indicate values that are significantly different from those of control mice (comparison between the black histograms of control and edelfosine-treated groups) at P<0.05 (*) and P<0.01 (**).