title: Immunosuppression with a combination of triptolide and cyclosporin A in rat vascularized groin flap allotransplantation.
abstract: BACKGROUND
  Triptolide is an immunosuppressive fraction purified from a Chinese medicinal plant. In an effort to develop a new immunosuppressive strategy for vascularized composite allotransplantation, the authors investigated the effects of combined treatment with cyclosporin A and triptolide on the survival of rat groin flap allotransplants.
  
  
  METHODS
  Groin flap transplantation was performed from Brown Norway rats to Fischer 344 recipients, which were then treated with triptolide, cyclosporin A, or both. Flap biopsy specimens were harvested, stained, and submitted to histopathologic evaluation. Levels of CCR5, CCR7, CCL19, CCL21, and Foxp3 in spleen were examined by real-time polymerase chain reaction, and the percentage of CD4+CD25+ regulatory T cells was detected by flow cytometry.
  
  
  RESULTS
  The mean survival time for allografts in recipients receiving triptolide and cyclosporin A was 57 ± 7.7 days compared with 20.5 ± 2.3 days for cyclosporin A alone, 23.3 ± 3.6 days for triptolide alone, and 7.8 ± 0.8 days for no treatment. Histologic examination also showed that inflammatory cell infiltration was reduced in grafts with combination treatment. Down-regulation of CCR5, CCR7, and CCL19 in the combination treatment was accompanied by increased expression of Foxp3. Flow cytometric analysis also revealed that the percentage of CD4+CD25+ regulatory T cells in the combination treatment was higher than in the monotherapy groups.
  
  
  CONCLUSIONS
  Combination therapy with triptolide and cyclosporin A substantially prolonged allograft survival, which means calcineurin inhibitor-related drug-toxicity may be alleviated and treatment cost reduced. This immunosuppressive effect is mediated by inhibition of dendritic cells maturation and the expansion of regulatory T cells.
authors: Shanghai, People's Republic of China; and Philadelphia, Pa. From the Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital; the Department of Orthopaedic Surgery, Hospital of the University of Pennsylvania; and McKay Orthopaedic Laboratory, University of Pennsylvania.
authors: Fei
authors: F
authors: Liu
authors: Xusong
authors: X
authors: Luo
authors: Shenghui
authors: S
authors: Lan
authors: Xianrong
authors: X
authors: Zhang
authors: Shoubao
authors: S
authors: Wang
authors: Jun
authors: J
authors: Yang
authors: L Scott
authors: LS
authors: Levin
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage*; D004224:Diterpenes / Q000008:administration & dosage*; D004852:Epoxy Compounds / Q000008:administration & dosage; D006119:Groin / Q000601:surgery; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D010616:Phenanthrenes / Q000008:administration & dosage*; D051381:Rats; D013524:Surgical Flaps / Q000098:blood supply*
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; C001899:triptolide; D016572:Cyclosporine