Differential effects of anti-Fas ligand and anti-tumor necrosis factor α antibodies on acute graft-versus-host disease pathologies

Both tumor necrosis factor alpha (TNF alpha) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD). In this study, we examined the ameliorating effects of neutralizing anti-FasL and/or anti-TNF alpha monoclonal antibody (MoAb) in a lethal acute GVHD model in mice. Whereas the treatment with either anti-FasL or anti-TNF alpha MoAb alone significantly delayed the mortality and improved the body weight, a complete protection was achieved by the administration of both MoAbs. Pathological examination indicated differential effects of anti-FasL or anti-TNF alpha MoAb on GVHD-associated pathologies. Hepatic lesion was improved by anti-FasL but not anti-TNF alpha MoAb. In contrast, intestinal lesion was improved by anti-TNF alpha but not anti-FasL MoAb, Cutaneous and splenic lesions were improved by either MoAb. The combination of both MoAbs improved ail these lesions, These results indicate that FasL and TNF alpha differentially contribute to the GVHD pathologies and a complete protection from mortality can be achieved by neutralization of both FasL and TNF alpha. (C) 1998 by The American Society of Hematology.