Therefore, efficient delivery of corticosteroids into the cytoplasm could enhance their therapeutic effect. It is known that a dexamethasone palmitate emulsion is readily taken up by macrophages via phagocytosis and is strongly retained in the cytoplasm. Here, we report that the macrophages increased in fatal GVHD are inflammatory and that DP treatment efficiently attenuated such GVHD by inhibiting macrophage functions. Inflammatory cells such as macrophages and mast cells have been proved to be durable to even high dose chemotherapy and irradiation. Accordingly, donor-cell CP-471474 chimerism analysis showed that.90% of dermal macrophages possessed the recipient phenotype. Macrophages are divided into two major classifications: classically activated, i.e. inflammatory, and alternatively activated, i.e. anti-inflammatory macrophages. Since persistence of macrophage activation can be harmful to the host, phenotypic switch from inflammatory macrophages to anti-inflammatory macrophages can be occurred via various stimuli. We revealed by RT-PCR that macrophages in the skin of a murine GVHD model possessed inflammatory properties although the macrophages in patients with GVHD expressed CD163, a marker of the alternatively activated macrophages. Recently, compelling studies revealed that CD163 + macrophages could be unrestrained proinflammatory macrophage population with an incomplete switch to anti-inflammatory macrophages under certain circumstances such as iron-overloading condition. An elevated level of ferritin, a marker of tissue iron overload, closely correlates with increased risk of acute GVHD, higher mortality and lower overall survival. These evidences and results suggest that CD163 + macrophages in patients with GVHD can be inflammatory and exacerbate GVHD similarly with the mouse GVHD model. CCL2-CCR2 signaling is known to play a major role in recruitment of monocytes/macrophages. Inflammatory mediators released from activated macrophages not only induce tissue damage but also recruit and activate macrophages.DP treatment in a mouse GVHD model decreased the number of macrophages in the skin and gut, and attenuated GVHD PD 168,077 maleate salt without severe complications compared to DSP treatment, suggesting that DP inhibited the positive feedback loop between macrophages and inflammation more efficiently than by DSP.