Evaluation of tetrahydropyranyladriamycin as an immunosuppressant in concordant xenotransplantation.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

THP can prevent early phase humoral rejection in concordant xenotransplantation.