Immunosuppression in nerve allografting: is it desirable?

Immunologically incompatible sciatic nerve grafts were inserted into the severed sciatic nerves of Wistar rats. In an attempt to induce graft tolerance, low-dose cyclosporin A (CsA) was administered to some animals for 20 weeks, then gradually withdrawn. Behavioural, electrophysiological and histological studies indicated that some degree of regeneration took place in all animals regardless of treatment. Neither a daily dose of 5 mg/kg nor 10 mg/kg was sufficient to prevent the rejection and subsequent disruption of allograft structure, and as a consequence reinnervation of the distal stump was limited. This was manifest both in the poor functional recovery of the denervated foot, and in the large number of regenerated axons found outside of the perineurial membranes of the transplanted fascicles. Therefore, tolerance was not induced at these doses. Furthermore, the significant decrease in the amplitude of electromyographs recorded from experimental and unoperated (control) animals suggests CsA may have a deleterious effect on unlesioned nerve even at these low doses. It would be prudent, therefore, to exercise caution in the combined use of nerve allografts and CsA immunosuppression, until the neurotoxicity of CsA has been investigated further. This is particularly important since CsA is sometimes used in the treatment of certain neuropathic autoimmune diseases.