STUDY OF THERAPY OF GRAFT VERSUS HOST DISEASE AFTER BONE MARROW TRANSPLANTATION USING MICE MODEL

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We studied therapy of graft versus host disease after bone marrow transplantation using mice model. The effect of Dexamethasone palmitate (D-PAL) incorporated into lipid microspheres (D-PAL emulsion) on chronic GVHD was studied with animal model. BALB/c mice were lethally irradiated and administered spleen cells and bone marrow cells from B10.D2 mice . These mice are identical at the major histocompatibility complex (MHC, H-2 d) and at the minor lymphocyte stimulating locus (Mls, b). Weeks after transplantation, the BALB/c recipients exhibit hair loss, weight loss and atrophy of the lymph nodes and spleen and finally died due to chronic GVHD. D-PAL emulsion was administered to this GVHD mice model to investigate the effect of that drug on GVHD and to compare the effects of D-PAL emulsion with those of the water-soluble steroid, methylprednisolone (m-PSL). When mice were treated with D-PAL emulsion at day 2 after transplantation and afterward once every 3 or 4 weeks, 94% of them were survived at week 20 and only 12% of them showed hair loss. These data were significantly better than mice administered m-PSL( survival rate: 63%) or without any treatments (survival rate: 37%). Autopsy revealed that the survived recipient mice administered D-PAL emulsion showed no significant changes in skin, lymph nodes, spleen and liver, while no-treated recipients and recipients administered m-PSL showed tissue reduction and destruction with T cell infiltration in those tissues even though they survived.