Anti-TNF-alpha and Pentoxifylline for Prophylaxis of aGvHD in Murine Allogeneic Bone Marrow Transplantation

Clinical studies analyzing sequential serum levels suggest pathophysiological involvement of Tumor-Necrosis-Factor-alpha (TNFa) in acute graft-versus-host disease (aGvHD) and endothelial complications following allogeneic bone marrow transplantation (BMT). For further investigation of the role of TNFa in aGvHD a neutralizing rb-anti-ms-TNFalpha antibody or pentoxifylline (PTX) as an inhibitor of TNFa-transcription were injected in lethally irradiated mice before or following transplantation of semi- or fully allogeneic bone marrow and various T-cell doses. Prophylactic application of anti-TNFa either prior to irradiation and BMT (p < .05) or at weekly intervals from d7 until d35 (p < .01) significantly reduced aGvHD-related mortality and cachexia, when low doses of semiallogeneic T cells were used for induction of aGvHD. Under these conditions, only a marginal protective effect could be obtained by long term application of PTX. In addition, aGvHD induced by high doses of T cells or by transfer of fully allogeneic T lymphocytes could not be prevented by anti-TNFa. These results further indicate that neutralization of TNFa might be helpful as an additive strategy for prevention of aGvHD especially in HLA-indentical BMT.