Rapamycin is highly effective in murine models of immune-mediated bone marrow failure.

Rapamycin is highly effective in murine models of immune-mediated bone marrow failure. Haematologica. 2017 Jul 20;: Authors: Feng X, Lin Z, Sun W, Hollinger MK, Desierto MJ, Keyvanfar K, Malide D, Muranski P, Chen J, Young NS Abstract Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure. Rapamycin ameliorated pancytopenia, improved bone marrow cellularity, and extended animal survival in a manner comparable to the standard dose of cyclosporine. Rapamycin effectively reduced Th1 inflammatory cytokines interferon-γ and tumor necrosis factor-α increased the Th2 cytokine interleukin-10; stimulated expansion of functional regulatory T cells; eliminated effector CD8+ T cells, notably T cells specific to target cells bearing minor histocompatibility antigen H60; and preserved hematopoietic stem and progenitor cells. Rapamycin, but not cyclosporine, reduced the proportion of memory and effector T cells and maintained a pool of naive T cells. Cyclosporine increased cytoplasmic nuclear fac...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research