Shuji Ikebe

Immunosuppressive effect of tacrolimus (FK-506): Bone xenografts in rabbits

We examined the immunomodulatory effect of the macrolide antibiotic FK-506 (tacrolimus) in bone xenograft transplantation. Full-thickness pieces of iliac bone from mongrel dogs were transplanted into the iliac bone of Japanese white rabbits. FK-506 at a dose of 1.6 mg/kg/day was injected into the rabbits for 10 days after transplantation. In the animals treated with FK-506, inflammatory cell infiltration was remarkably reduced and revascularization accompanied by new bone formation occurred in the grafts. At 4 months after the transplantation, the formation of new bone and of mature new bone marrow were observed. In a control group, inflammatory cell infiltration was marked around the graft from 2 weeks after the transplantation. Revascularization from the recipient site to the graft in the control group was poor and only a small amount of new bone had formed at 4 months. Our findings suggest that short-term administration of FK-506 has a beneficial effect on experimental xenograft bone transplantation.

Osteogenesis in xenogeneic bone transplantation, using an immunosuppressant: Rabbit-rat experiments

We investigated osteogenesis and lymphocyte subsets in xenogeneic bone transplantation, using the immunosuppressant FK506 (FK). Iliac bones of rabbits were transplanted as fresh and frozen xenogeneic bone grafts into an intramuscular pouch of rats. FK was injected intramuscularly in half of the rats in a dose of 3 mg/kg/day for 14 days after transplantation. At 2, 4, and 8 weeks, transplanted grafts and the lymphocyte subsets of these rats were examined. In the group not given FK, the grafted bone became necrotic and infiltrated with small round cells around the trabeculae. In the FK group, at 2 and 4 weeks, new bone was formed in the fresh xenografts without infiltration of lymphocytes. At 8 weeks, the new bone became necrotic and lymphocytes were present. The percentage of T cells (CD 5), B cells and the ratio of CD 4 cells/CD 8 cells were smaller in the FK group. Using an immunosuppressant we concluded that xenogeneic bone has an osteogeneic potency.