FK506 rescues peripheral nerve allografts in acute rejection

This study investigated the ability of the immunosuppressant FK506 to rever se nerve allograft rejection in progress. Eighty-four Buffalo rats received posterior tibial nerve grafts from either Lewis or Buffalo donor animals. Allografts were left untreated for either 7, 10, or 14 days before receivin g daily subcutaneous FK506 injections (2 mg/kg). Time-matched control anima ls received either an isograft, an allograft with continuous FK506, or an a llograft with no postoperative FK506 therapy. All animals underwent weekly evaluation of nerve function by walking track analysis. Experimental group animals were sacrificed either immediately prior to initiation of FK506 the rapy (days 7, 10, or 14), after 2 weeks of immunosuppressive treatment, or 8 weeks postsurgery. Histomorphometric analysis, consisting of measurements of total number of nerve fibers, neural density, and percent of neural deb ris, demonstrated a statistically significant increase in regeneration in t he isograft group relative to the untreated allograft group within 28 days of transplantation. Grafts harvested from animals receiving 2 weeks of FK50 6 after 7 or 10 days of rejection were histomorphometrically similar to tim e-matched isografts. By contrast, grafts from animals receiving 2 weeks of FK506 following 14 days without therapy resembled untreated allografts and demonstrated significant histomorphometric differences from isografts at th e corresponding time point. Analysis of walking track data confirmed that r elative to untreated allografts, functional recovery was hastened in animal s receiving an isograft, or allograft treated with FK506. This study demons trated that when started within 10 days of graft placement, FK506 could rev erse nerve allograft rejection in rats evaluated following 2 weeks of treat ment.