Low dose discontinued FK506 treatment enhances peripheral nerve regeneration.

ABSTRACT

FK506 has been reported to enhance nerve regeneration in various rodent models. However, both the immunosuppressive properties and potential side effects may preclude the broad clinical use of FK506 to speed nerve regeneration. In this study, we examined the nerve regenerative property of a low, nonimmunosuppressive dose (0.5 mg/kg/day) of FK506. Two treatment schedules (continuous versus discontinuous) were compared. Evaluations were perforrmed at 1, 2, and 3 months. The gastrocnemius muscle mass was significantly higher in treated groups compared with the untreated group at 3 months, and the total number of fibers, percentage of neural tissue, fiber density, and fiber diameter were greater in treated groups than in the untreated group. However, at 3 months there was no difference in these parameters between groups in which FK506 was administered continuously and those in which the drug was stopped at 2 months. This study confirms that daily administration of low dose FK506 enhances peripheral nerve recovery after transection injury.