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
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
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DOI：
10.1097/00007890-200208270-00004
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发表时间：
2002-08-27
期刊：
影响因子：
6.2
通讯作者：
Chen, ZQ
中科院分区：
文献类型：
--
作者：
Fidler, JM;Ku, GY;Chen, ZQ
背景PG 27是从中药雷公藤提取物中分离纯化的有效部位。我们在小鼠异基因骨髓移植（BMT）中检测PG 27，并研究其抑制移植物抗宿主病（GVHD）的机制。C57 BL/6 --> BDF 1小鼠BMT模型中的受体接受口服或腹腔内PG 27。口服或腹腔内给予14天的PG 27可防止GVHD的发展，并使许多动物的无病生存期延长（超过300天）。PG 490 -88是PG 490（雷公藤内酯醇，存在于PG 27中）的半合成衍生物，也有效。与媒介物处理的小鼠相比，PG 27使第7天脾同种异体特异性细胞毒性T淋巴细胞水平降低超过99%。与正常小鼠相比，对照同种异体BMT小鼠的脾脏显示单核细胞含量显著降低，CD 8+细胞百分比增加，CD 4+细胞减少，活化的（[白细胞介素-2受体+]，IL-2 R+）CD 8 + T细胞增加。PG 27增加了单核细胞的恢复，并显着降低了异基因BMT小鼠第14天CD 3+和IL-2 R+细胞的百分比，产生的结果与同基因BAIT小鼠相似。PG 27显著增加了伴刀豆球蛋白A刺激的体外IL-4的产生，其水平比对照细胞高7- 8倍。仅14天的PG 27处理阻止了GVHD的诱导和发展，并产生了长期存活。PG 27在很大程度上使脾T淋巴细胞亚群正常化，降低同种异体细胞毒性T淋巴细胞活性，并增加IL-4产生能力。PG 27可以通过诱导无反应性和远离促炎表型来抑制GVHD，这可以反映在IL-4产生的增加的潜力中。
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.