Tumor necrosis factor inhibitor ameliorates murine intestinal graft-versus-host disease

Background & Aims: Transfer of T helper cells from DBA/2 mice to irradiated allogeneic B6D2F1 mice leads to development of colonic graft-versus-host d isease with pathological features of inflammatory bowel disease. To examine the role of tumor necrosis factor (TNF) in graft-versus-host disease enter opathy, an adenoviral vector encoding a TNF inhibitor protein was administe red. Methods: Irradiated B6D2F1 mice were infused with DBA/2 bone marrow an d spleen cells. Mice then received either a control beta-galactosidase-enco ding adenovirus or an adenovirus encoding a TNF inhibitor, composed of the extracellular domain of the human 55-kilodalton TNF receptor linked to the murine immunoglobulin G1 heavy chain. Mucosal permeability to sucralose and colonic histology were assessed 14 and 25 days after transplantation. Resu lts: Less diarrhea was observed in DBA/2 --> B6D2F1 mice expressing the TNF inhibitor, and colonic sections from these mice had significantly less inf lammation and epithelial cell abnormalities. In TNF inhibitor recipients, m ucosal permeability to sucralose was similar to that in nonirradiated contr ol mice and significantly less than in recipients of the control adenovirus . Conclusions: TNF inhibition decreases the severity of enteropathy in the DBA/2 --> B6D2F1 murine model of colonic graft-versus-host disease.