Short-course immunosuppression using FK506 for rat tracheal allografts

A minimizing immunosuppression after a tracheal allotransplantation is desirable.

We examined the usefulness of a short-course of immunosuppression after tracheal allotransplantation in rat. Each transplant consisting of a 5-ring segment was heterotopically implanted into the omentum. Four animals underwent a syngeneic transplantation and thus served as controls (Group A). Thirty animals underwent an allogeneic transplantation and were randomly classified into 4 groups as follows: No immunosuppression (Group B, n=6), treatment with 0.5 mg/kg of Tacrolims (FK506) (Group C, n=8), 1.0 mg/kg of FK506 (Group D, n=8), and 1.5 mg/kg of FK506 (Group E, n=8). Different doses of FK506 were administered intramuscularly for only three consecutive days after heterotopic tracheal allotransplantation. The serum levels of FK506 were then investigated 3, 7, 14, 21, and 28 days after transplantation in groups C, D, and E. All rats were killed 28 days after transplantation and then the implanted tracheae were harvested, and evaluated histologically.

All animals survived for the protocol period. The graft morphology of Group E was significantly better than that of groups B, C, and D regarding both macro- and microscopy, and also showed the same findings as that of Group A, except for low-grade mononuclear cell infiltration. Only in Group E, the FK506 blood level was maintained at over 0.5 ng/ml, which is the lowest detectable limit in this assay, until 21 days after transplantation.

We thus conclude that 1.5 mg/kg of FK506 which was administered for only three consecutive days after surgery may be used to maintain the morphology of tracheal allografts in rats for 28 days after transplantation.