osi-027 and Postoperative-Complications

Despite its rarity (1%-2%), acute graft-versus-host disease after liver transplantation (LT-aGVHD) has a high mortality rate (85%). A gradual decrease in regulatory T cells (Tregs) correlates with disease progression in a rat LT-GVHD model, and treatments which increase Tregs exert therapeutic effects on LT-aGVHD. In this study, LT-aGVHD model rats were treated with rapamycin (RAPA), OSI-027, or an equal quantity of vehicle. Rats treated with OSI-027 survived longer (>100 days) than those in the RAPA (70 ± 8 days) or control (24 ± 3 days) groups. Flow cytometric analysis showed that the Treg ratios in peripheral blood mononuclear cells in the OSI-027 group were higher than those in the RAPA or control groups. The proportions of donor-derived lymphocytes in the OSI-027 group were lower than those in the RAPA or control groups. Hematoxylin-eosin staining of skin tissue demonstrated less severe lymphocyte infiltration in the OSI-027 group than that in the RAPA or control groups. In vitro, OSI-027 induced differentiation of CD4

Topics: Acute Disease; Allografts; Animals; Cell Differentiation; Disease Models, Animal; Disease Progression; Female; Forkhead Transcription Factors; Graft vs Host Disease; Humans; Imidazoles; Immunosuppressive Agents; Leukocyte Count; Leukocytes, Mononuclear; Liver Transplantation; Postoperative Complications; Rats; Rats, Inbred Lew; Sirolimus; Specific Pathogen-Free Organisms; T-Lymphocytes, Regulatory; Triazines