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Immunosuppressive activity of the Chinese medicinal plant Tripterygium wilfordii. III. Suppression of graft-versus-host disease in murine allogeneic bone marrow transplantation by the PG27 extract

作者 Fidler, JM; Ku, GY; Piazza, D; Xu, RS; Jin, RL; Chen, ZQ

期刊 TRANSPLANTATION , AUG 27 2002,4:74

DOI 10.1097/00007890-200208270-00004 PubMed 12352901

摘要 Background. PG27 is an active fraction purified from an extract of a Chinese medicinal plant, Tripterygium wilfordii Hook L We tested PG27 in murine allogeneic bone marrow transplantation (BMT) and investigated the mechanism of graft-versus-host disease (GVHD) suppression.Methods. Recipients in the C57BL/6 --> BDF1 murine BMT model received oral or intraperitoneal PG27.Results. Fourteen days of PG27 given orally or intraperitoneally prevented GVHD development and produced extended disease-free survival (more than 300 days) for many animals. PG490-88, a semisynthetic derivative of PG490 (triptolide, present in PG27), was also efficacious. PG27 reduced day 7 splenic allospecific cytotoxic T lymphocyte levels by more than 99% compared with vehicle-treated mice. Compared with normals, spleens from control allogeneic BMT mice displayed significantly reduced mononuclear cell content, an increased percentage of CD8+ cells, fewer CD4+ cells, and more activated ([interleukin-2 receptor+], IL-2R+) CD8+ T cells. PG27 increased mononuclear cell recovery, and significantly reduced the day-14 percentages of CD3+ and IL-2R+ cells in allogeneic BMT mice, producing results similar to those for syngeneic BAIT mice. PG27 significantly increased concanavalin A-stimulated in vitro IL-4 production by day-14 splenocytes, with a 7- to 8-fold higher level than that produced by control cells.Conclusions. PG27 treatment for only 14 days prevented GVHD induction and development and produced long-term survival. PG27 largely normalized splenic T lymphocyte subsets, reduced allospecific cytotoxic T lymphocyte activity, and increased IL-4 production capability. PG27 may suppress GVHD by the induction of anergy and a deviation away from a proinflammatory phenotype, which could be reflected in the increased potential for IL-4 production.

涉及物种 雷公藤 Tripterygium wilfordii