Effect of 15-deoxyspergualin on allograft arterio-sclerosis and growth factor synthesis in the rat.
ABSTRACT Chronic rejection is a major cause for late graft loss. Typical vascular changes in the grafts are adventitial inflammation, disappearance of myocytes in the media and thickening of the intimal layer. We investigated the effect of a new immunosuppressive drug, 15-deoxyspergualin (DSG), on chronic rejection using our rat aortic allograft model. At the dose of 1.0 mg/kg per day, DSG significantly reduced all histopathological parameters of chronic rejection, thus, inhibiting the generation of allograft arteriosclerosis. Growth factor synthesis in the grafts was determined by reverse transcription reaction with oligo dT primers and semiquantitated by polymerase chain reaction. The expression of several growth factors, PDGF-BB, IGF-1, EGF an TGF-beta, was suppressed to 16-60% of the non-treated allograft level. This indicated that DSG may work via suppression of growth factor synthesis and, thus, inhibits the generation of chronic rejection.
Chapter: Transplant Arteriopathy[Show abstract] [Hide abstract]
ABSTRACT: The concept of surgically replacing diseased tissue with healthy tissue to treat end-stage organ failure fo Toit rms the foundationof clinical transplantation. The science and technique of transplantation trace their origins to the beginning of last century. First tried in the 1950s, solid organ transplantation did not become a credible therapeutic option until the advent of chemical immunosuppression, especially cyclosporine use, in the early 1980s. The recent use of powerful immunosuppressive agents, such as the calcineurin inhibitors cyclosporine A (CsA) and tacrolimus (FK506), in combination with azathioprine or mycophenolate mofetil and steroids has helped to overcome the problem of acute allograft rejection. One-year graft survival rates are currently approximately 90% for most types of transplanted organs. Despite improvements in short-term outcome, the half-life of organ allografts has only marginally increased over the past 20 yr. Long-term organ survival is questionable in patients who have had at least one episode of acute rejection (1). Chronic allograft rejection and drug-related toxicity are the main obstacles to indefinite graft survival.12/2004: pages 243-270;