sirolimus and Bone-Marrow-Diseases

Topics: Angiogenesis Inhibitors; Animals; Apoptosis; Atherosclerosis; Bone Marrow Diseases; Cell Division; Clinical Trials as Topic; Cyclosporine; Graft Rejection; Graft vs Host Disease; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Lymphocyte Subsets; Mice; Multicenter Studies as Topic; Muscle, Smooth, Vascular; Neoplasms; Postoperative Complications; Sirolimus; TOR Serine-Threonine Kinases; Wound Healing

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 with anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In this 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

Topics: Anemia, Aplastic; Animals; Bone Marrow; Bone Marrow Diseases; Bone Marrow Failure Disorders; Disease Models, Animal; Epitopes, T-Lymphocyte; Hemoglobinuria, Paroxysmal; Immunologic Memory; Immunosuppressive Agents; Mice; Pancytopenia; Signal Transduction; Sirolimus; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Treatment Outcome

Topics: Bone Marrow Diseases; Cell Survival; Dose-Response Relationship, Drug; Graft vs Host Disease; Humans; Severity of Illness Index; Sirolimus; Stem Cells