dehydroxymethylepoxyquinomicin and Graft-vs-Host-Disease

GVHD is a crucial mortality factor in allogeneic bone marrow transplantation (ABMT). In this paper, we show that dehydroxymethylepoxyquinomicin (DHMEQ), a novel inhibitor of nuclear factor-κB, suppresses GVHD, resulting in an improved mortality rate in a mouse ABMT model. Bone marrow cells from C57BL/6 mice (B6 mice) were transplanted into lethally irradiated BALB/c mice. Two weeks later, spleen cells from B6 mice were transplanted into the irradiated BALB/c mice. From one week after the injection of spleen cells, when the mice started to show GVHD, the mice were also injected intraperitoneally daily with DHMEQ or vehicle only (DMSO) for 4 weeks. By 80 days after the ABMT, 6/14 of the vehicle-injected mice (43%) had died because of GVHD, whereas all DHMEQ-injected mice survived this observation period and developed milder GVHD than the vehicle-injected mice. When regulatory T cells were reduced by the injection of anti-folate receptor 4 (FR4) antibody, the effects of DHMEQ were reduced. These findings suggest that administration of DHMEQ could become a new strategy for preventing fatalities from GVHD.

Topics: Animals; Antibodies; Benzamides; Bone Marrow Transplantation; Cell Proliferation; Cyclohexanones; Cytokines; Graft vs Host Disease; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; NF-kappa B; Receptors, Cell Surface; Spleen; Survival Rate; T-Lymphocytes, Regulatory; Transplantation, Homologous