Yasutomi M, Hayashi S, Ito M, Ohtsuka S, Namii Y, Uchida K, Yokoyama I, Takagi H
Department of Surgery II, Nagoya University, School of Medicine, Japan.
J Heart Lung Transplant. 1997 Mar;16(3):283-9.
Tetrahydropyranyladriamycin (THP), a derivative of anthracycline, exhibits a stronger antiproliferative activity and a lower cardiotoxicity than the other anthracyclines. The value of THP as an immunosuppressant has not been examined yet, whereas cyclophosphamide, which is another antiproliferative drug, has shown promise as an immunosuppressant in concordant xenotransplantation.
The effect of THP on the marginal zone in the spleen and anti-species antibody production was evaluated and was compared with that of cyclophosphamide in a concordant xenogeneic splenocyte injection model (hamster-to-rat). Next, THP was used as monotherapy for hamster-to-rat heart transplantation to substantiate the potency of its immunosuppressive activity in concordant xenotransplantation. Finally, combination therapy with THP plus FK506 was tried.
THP (5 mg/kg) suppressed the expansion of the marginal zone more than did cyclophosphamide (40 mg/kg) and inhibited the production of antispecies antibody as much as did cyclophosphamide (40 mg/kg) in the splenocyte injection model. THP monotherapy could prolong the survival of hamster-to-rat heart grafts up to 14.5 +/- 3.2 days (n = 21). The rejected grafts in the THP-treated animals did not show any histologic evidence of vascular endothelial damage but did exhibit a mononuclear cell infiltration. Combination therapy with THP plus FK506 provided excellent graft survival.
THP can prevent early phase humoral rejection in concordant xenotransplantation.
四氢吡喃阿霉素（THP）是一种蒽环类衍生物，与其他蒽环类药物相比，具有更强的抗增殖活性和更低的心脏毒性。THP作为免疫抑制剂的价值尚未得到研究，而另一种抗增殖药物环磷酰胺在协调性异种移植中已显示出作为免疫抑制剂的前景。
在协调性异种脾细胞注射模型（仓鼠到大鼠）中评估THP对脾脏边缘区的影响和抗种属抗体产生，并与环磷酰胺进行比较。接下来，将THP用于仓鼠到大鼠心脏移植的单一疗法，以证实其在协调性异种移植中免疫抑制活性的效力。最后，尝试THP加FK506的联合疗法。
在脾细胞注射模型中，THP（5mg/kg）比环磷酰胺（40mg/kg）更能抑制边缘区的扩张，并且与环磷酰胺（40mg/kg）一样能抑制抗种属抗体的产生。THP单一疗法可使仓鼠到大鼠心脏移植物的存活期延长至14.5±3.2天（n = 21）。接受THP治疗的动物中被排斥的移植物没有显示出任何血管内皮损伤的组织学证据，但确实表现出单核细胞浸润。THP加FK506的联合疗法提供了出色的移植物存活情况。
THP可预防协调性异种移植中的早期体液排斥反应。
