Graft versus host disease (GVHD) remains a major complication of allogenic bone marrow transplantation (BMT). GVHD is a systemic inflammatory response initiated by the activation of donor T cells, and which expands to include other inflammatory cells such as monocytes. An important aspect of the inflammation of GVHD is the dysregulation of cytokines. These cytokines include tumor necrosis factor (TNF), Interferon-gamma, Interleukin 1 (IL-1) and Interleukin 2 (IL-2). These cytokines have been implicated in the pathogenesis of allogenic reactions such as GVHD as well as allograft rejection. In a mouse model, TNF mRNA levels have been found to be elevated during GVHD, and the use of a polyclonal anti-TNF antibody partially prevents GVHD mortality. The nature and extent of cytokine dysregulation after transplantation, and in particular during GVHD are unknown. The study looks to understand the nature of production GVHD and how immunosuppressive drugs affect that production. The results of this study could be useful in designing future bone marrow transplant protocols. The objectives of the research are as follows: 1) To determine the serum levels of the following cytokines before the start of immunosuppressive therapy for (GVHD): Tumor Necrosis Factor, IL-1, IL-2, Interferon-gamma; 2) to determine the serum levels of the cytokines 72 hours after initiation of immunosuppressive therapy; 3) to measure the amount of mRNA of those same cytokines in the peripheral blood cells of patients at the initiation of immunosuppressive therapy, and 72 hours later.

Project Start
Project End
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
16
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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