Effects of donor pretreatment with antilymphocyte serum and cyclosporin on rejection and graft-versus-host disease after small bowel transplantation in immunosuppressed and nonimmunosuppressed rats

Abstract

After fully allogeneic small bowel transplantation, both graft-versus-host disease (GVHD) and rejection may occur. Donor pretreatment may prevent GVHD, but this sometimes leads to accelerated graft rejection. To study a possible balance between GVHD and rejection, fully allogeneic total orthotopic small bowel transplantation was performed in rats using the WAG-to-BN donor-host combination. Untreated control grafts were rejected in 16.6 +/- 2.7 days (mean +/- SEM), and 35% of the animals had mild, transient GVHD. Pretreatment of the donor with antilymphocyte serum on days -2 and -1 before grafting, with antilymphocyte serum on days -2 and -1 before grafting, with antilymphocyte serum on days -2 and -1 before grafting, either intravenously or intraperitoneally, completely eliminated the occurrence of clinical GVHD but led to significantly shortened survival times (12.3 +/- 0.8 and 10.3 +/- 0.9 days, respectively). Donor pretreatment with 50 mg/kg cyclosporin (CyA) on days -2 and -1 prolonged graft survival significantly to 22.1 days but had no significant effect on the incidence of GVHD. Administration of 25 mg/kg CyA on days 0, 1, 2, 4, and 6 after grafting prolonged survival to 38.3 days with no evidence of GVHD. Pretreatment of the donor with antilymphocyte serum (ALS), combined with the same postoperative, short-term CyA regimen, increased survival to more than 50 days, again with no evidence of GVHD. When CyA was used as both donor pretreatment and postoperative therapy, there was no survival advantage compared to the use of postoperative CyA alone. These results show that an in vivo balance between GVHD and rejection exists and that abrogation of GVHD leads to accelerated rejection.(ABSTRACT TRUNCATED AT 250 WORDS)