Effect of FK506 on limb-allograft in rats. A preliminary report.:A Preliminary report

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The effects of short and long term treatment with FK506 (FK), a new immunosuppressive macrolide, on rat limb-allograft were investigated across the BN-to-F344 histocompatibility barrier. This vascularized composite tissue allograft model represents a strong and major transplantation barrier. In this combination, median limb-allograft survival time (MST) measured by the first visual signs of skin rejection was 11±0.7 (mean±SD) days when recipient rats received no immunosuppressive treatments. In the first set of experiments, dose-response studies of FK were carried out in a 14-day course of treatment in which a total of 15 rats received daily intramuscular administration of FK at a dose of 0.2, 1.0, or 5mg/kg/day for 14 days, begun on the day of transplantation. By daily treatment with FK at a dose of 1.0mg/kg or more, limb-allograft survival times dramatically prolonged; i. e., MST was 15±2.6 days in the 0.2mg/kg group, 129±50 days in the 1.0mg/kg group and 101±9 in the 5mg/kg group. In the next set of experiments, we wished to see if a single treatment with FK would have similar effects on graft survival. In other words, groups of rats received single administration of FK at a dose of 2, 10 or 50mg/kg only on the day of operation. Surprisingly, this regimen of FK-treatment also prolonged limb survival time in a dose-dependent manner. MST was 16±3 days in the 2mg/kg group, 51±7 days in the 10mg/kg group and 104±17 days in the 50mg/kg group. These results show the effectiveness of FK-treatment on this animal model of limb-allograft and suggest the possibility of composite tissue allograft in humans.
西日本整形・災害外科学会の論文

Effect of FK506 on limb-allograft in rats. A preliminary report.:A Preliminary report

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