Effect of glucosidorum tripterygii tororum on acute graft-versus-host disease in mice.

To prevent acute graft-versus-host disease (aGVHD), glucosidorum tripterygii tororum (GTT) was used in the murine model. The lethally irradiated C57BL/6 recipients were injected with bone marrow and lymphocyte grafts from BALB/c donors and were treated intraperitoneally with GTT, cyclosporine A (CsA), or methotrexate (MTX). T lymphocytes, adhesion molecules and cytokines were detected by immunohistochemical method, flow cytometry, ELISA and RT-PCR, respectively. The results showed that all the control recipient mice (21/21) died of aGVHD within 30 days, but many recipient mice treated with GTT (19/21), CsA + MTX (13/21) and GTT + CsA (17/21) survived beyond 30 days without obvious signs of aGVHD. The numbers of CD3(+), CD4(+), CD8(+), CD11a(+), CD18(+) lymphocytes in skin and lung decreased markedly by GTT, GTT + CsA and CsA + MTX treatments. The numbers of CD3(+), CD4(+), CD8(+), CD4(+)CD11a(+), CD4(+)CD18(+), CD8(+)CD11a(+), CD8(+)CD18(+) lymphocytes in spleen decreased markedly by GTT, GTT + CsA and CsA + MTX treatments. and the changes of CD3(+), CD4(+), CD8(+) cells in small intestine were not remarkable (P > 0.05) by above mentioned GTT, GTT + CsA and CsA + MTX treatments. The serum concentrations and mRNA expressions of IL-2 and TNFalpha in spleens decreased significantly (P < 0.05); the concentration of IL-10 increased significantly (P < 0.05), the change of IL-4 was not remarkable (P > 0.05) by GTT treatment. It is concluded that the GTT may retain the graft-versus-leukemia (GVL) effect of transplant without aGVHD. The role of GTT in prevention of murine aGVHD is mediated by reduction of T lymphocytes and their subgroups, expression of adhesion molecule, and regulation of cytokine secretion.