DIFFERENTIAL-EFFECTS OF ANTI-FAS LIGAND AND ANTITUMOR NECROSIS FACTOR-ALPHA ANTIBODIES ON ACUTE GRAFT-VERSUS-HOST DISEASE PATHOLOGIES

Both tumor necrosis factor alpha (TNF alpha) and Fas ligand (FasL) hav e been implicated in the pathogenesis of graft-versus-host disease (GV HD). In this study, we examined the ameliorating effects of neutralizi ng anti-FasL and/or anti-TNF alpha monoclonal antibody (MoAb) in a let hal acute GVHD model in mice. Whereas the treatment with either anti-F asL or anti-TNF alpha MoAb alone significantly delayed the mortality a nd improved the body weight, a complete protection was achieved by the administration of both MoAbs. Pathological examination indicated diff erential effects of anti-FasL or anti-TNF alpha MoAb on GVHD-associate d pathologies. Hepatic lesion was improved by anti-FasL but not anti-T NF alpha MoAb. In contrast, intestinal lesion was improved by anti-TNF alpha but not anti-FasL MoAb, Cutaneous and splenic lesions were impr oved 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 mor tality can be achieved by neutralization of both FasL and TNF alpha. ( C) 1998 by The American Society of Hematology.