Objective To evaluate the inhibition effect of rapamycin(RAPA) on acute graft-versus-host disease(aGVHD) after allogeneic hemopoietic stem cell transplantation(allo-HSCT) in a murine model.Methods aGVHD was induced in female BALB/c(H-2d) mice by total-body irradiation(TBI) followed by male allogeneic[C57BL/6J,(H2b)] bone marrow transplantation.aGVHD was assessed both physically and histologically.Severe aGVHD was developed in the recipients.After allo-HSCT,mice were divided into 5 groups.Group 1 was given RAPA(1.5 mg·kg-1· d-1),group 2 CsA(1.5 mg·kg-1·d-1) and MTX(0.4 mg·kg-1·d-1),group 3 RAPA in combination with CsA and MTX,group 4 no agents for aGVHD prophylaxis,and group 5 with no transplantation.The physicalsigns,MST,peripheral blood counts,and aGVHD histopathologic examination were observed in all recipients.Results Mice in group 4 developed typical aGVHD and 100 % of mortality,with a mean survival time(MST) of 6 days.The MSTs of group 1-3 were significantly longer than that of group 4,being 3.5,1.9,6.0 days longer(P<0.05).There was no statistical difference in peripheral blood count among groups 1-3.Histopathological examination of skin,liver,and gastrointestinal tract showed typical signs of aGVHD in allo-HSCT recipients.Mice received immunosuppressive agents(RAPA,CsA,MTX) showed the less severe signs.Conclusions RAPA can markedly inhibit T cell proliferative response in vitro and markedly prolong MST of allo-HSCT recipients,delay the onset of aGVHD signs.The prophylaxis effect of CsA plus MTX with RAPA is better than that of RAPA alone.RAPA can decrease GVHD incidence after allo-HSCT in mice. |
