C. sinensis ablates allograft vasculopathy when used as an adjuvant therapy with cyclosporin A.
Immunosuppressive treatments are available to suppress acute cardiac rejection; however, no viable treatment exists for long-term cardiac graft failure. Moreover, extended use of calcineurin inhibitor immunosuppressants, the mainstay of the current therapeutic for cardiac transplantation, leads to significant associated pathologies such as nephrotoxicity and increased risk of cardiac disease. For the last ten years alternatives to calcineurin inhibitors, or adjuvant therapies designed to complement their activities, have been explored. In tandem with this development, there has been considerable interest in Traditional Chinese Medicines (TCM) as sources for novel therapeutics. Our study examines the ability of the TCM Cordyceps sinensis to reduce acute and chronic rejection associated with cardiac transplantation. The objectives of this study were to first determine if oral delivery of the extract could reduce acute rejection in a rat heterotopic heart model of transplantation. The second objective was to determine, in vitro, if a sterile, aqueous extract of C. sinensis could decrease CD8+ T cell activity. The third objective was to determine if oral delivery of the extract could ablate allograft vasculopathy in a mouse abdominal aortic transplant model. We found that oral delivery of the extract demonstrated a reduction in acute rejection when used in conjunction with a sub-therapeutic dose of Cyclosporine. Further, we found, using a mixed lymphocyte reaction, that the extract was able to significantly reduce CD8+ T cell activity. Finally, we demonstrate that oral delivery of the extract, used with a therapeutic dose of Cyclosporine to suppress acute rejection, ablates allograft vasculopathy.
Jordan
J L
JL
Department of Pathology, Dalhousie University, 5850 College Street, Halifax NS B3H 1X5, Canada.
Hirsch
G M
GM
Lee
T D G
TD
D000284:Administration, Oral; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002908:Chronic Disease; D003131:Combined Modality Therapy; D032661:Cordyceps; D016572:Cyclosporine / Q000008:administration & dosage*; D004357:Drug Synergism; D006083:Graft Occlusion, Vascular / Q000276:immunology / Q000517:prevention & control*; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D016572:Cyclosporine