THE IMMUNOSUPPRESSANT FK506 INCREASES FUNCTIONAL RECOVERY AND NERVE REGENERATION FOLLOWING PERIPHERAL-NERVE INJURY

Regeneration of peripheral nerve fibers over long distances often requ ires extended periods of convalescence. Loss to society can be measure d in terms of increased health care costs, decreased productivity and, in the case of job-related injuries, larger workers' compensation cla ims. The availability of drugs to increase axonal regeneration would b e beneficial not only to patients but also to society in general by de creasing these costs. In the present paper, we present our initial stu dies on the regenerative effects of the new immunosuppressive agent FK 506. Rats given a sciatic nerve crush (axotomy) received daily subcuta neous injections of FK506 (1.0 mg/kg); axotomized control animals rece ived saline. Clinical signs of recovery in the hind feet were manifest ed two days earlier in FK506-treated than in saline-treated animals; m ovement in the toes, and walking on the hind feet and toes were observ ed at 16 and 17 days, respectively, in saline-treated rats and at 14 a nd 15 days, respectively, in FK506-treated rats. Measurement of interd igit distances in the hind feet at 18 days following axotomy showed a return toward normal position of the toes (increased interdigit distan ces) during walking in FK506-treated rats. Light and electron microsco py performed at 18 days following axotomy confirmed the clinical appea rance of increased functional recovery in FK506-treated rats. Distal t o the crush site, the sciatic nerve and its terminal branches from FK5 06-treated animals contained more myelinated fibers compared to saline -treated animals; in the soleus nerve, the numbers of myelinated axons was increased 2.75-fold. Taken together, the present results suggest that FK506 enhances recovery of function in the rat by increasing the rate of axonal regeneration following a sciatic nerve crush.