THE IMMUNOSUPPRESSIVE EFFECT OF RAPARMYCIN ON MOUSE SMALL-BOWEL TRANSPLANTATION

The efficacy of rapamycin (RAPA) was tested on small bowel transplanta tion in the mouse and compared with cyclosporine (CsA). Four groups we re involved, each one included three combinations (n greater than or e qual to 6) for evaluation of host-versus-graft (HVG, C57BL/6xBALB/c F- 1 (CB6F(1))-to-BALB/c), graft-versus-host (GVH, BALB/c-to-CB6F(1)), an d combined HVG and GVH responses (C57BL/6-to-BALB/c), Grafts were tran splanted to recipients heterotopically. Groups were as follows: group 1: naive controls; groups 2 and 3: recipient mice treated with RAPA 2 mg/kg/day and 4 mg/kg/day orally for 14 days, respectively; group 4: r ecipient mouse treated with CsA 4 mg/kg/day orally for 14 days. In the HVG model, the mean survival time (MST) of recipients was significant ly longer in group 2 (32.9 +/- 17.7 days, P=0.006), group 3 (32.7 +/- 10.4 days, P=0.0001), and group 4 (37.9 +/- 11.8 days, P=0.0001), comp ared with naive controls in group 1 (8.5 +/- 1.6 days). In the GHV mod el, the MST of recipients in group 2 (41.8 +/- 19.9 days, P=0.002), gr oup 3 (48.2 +/- 21.4 days, P=0.001) and group 4 (56.5 +/- 30.6 days, P =0.003) were significantly prolonged compared with control group 1 (8. 5 +/- 1.6 days). In combined HVG and GVH responses, MST of recipient i n group 2 (20.9 +/- 4.9 days, P=0.0001), group 3 (27.0 +/- 4.3 days, P =0.008), and group 4 (35.2 +/- 23.9 days, P=0.0001) were also signific antly longer than that in controls (6.9 +/- 1.4 days), but in all thre e combinations, there were no statistically significant differences be tween groups 2 and 3, groups 2 and 4, or groups 3 and 4 (P>0.05). RAPA is a potent immunosuppressant able to significantly prolong small bo wel allograft survival in mice using a short-term treatment, There is no statistically difference in recipient survival between low and high doses of RAPA treatment and the CsA standard dose used in this study.