Effects of FK-506 and CTLA4--Ig on nerve allografts in mice

The purpose of this study is to evaluate the effects of FK-506 and cytotoxic T lymphocyte-associated antigen-4 immunoglobulin fusion protein (CTLA4--Ig) on nerve allografts. Adult male inbred C3H mice (mean weight, 25 g) surgically received 8 mm posterior tibial nerve defects, and donor nerve allografts from donor male C57BL mice were implanted. The experimental animals were divided into five groups of 12 animals each that were distinguished from each other by administration of FK-506 and CTLA4--Ig, that is, isografts interposed in the gap between contralateral posterior tibial nerves (group A, positive control); allografts from C57BL mice implanted without administering any treatment (group B, negative control); allografts from C57BL mice implanted and FK-506 injections administered (group C); allografts from C57BL mice implanted and CTLA4--Ig injections administered (group D); and allografts from C57BL mice implanted and FK-506 and CTLA4--Ig injections administered (group E). Postoperative walking-track functional analysis and histomorphometric studies were then conducted. Data were statistically analysed using the Kruskal-Wallis test. Compared with the negative control (group B), mice treated with both FK-506 and CTLA4--Ig (group E) demonstrated better results at 3 weeks post operation. Similar values were observed in all groups, and there were no statistical differences at 6 weeks post operation. Our results demonstrate that a co-administration of FK-506 and CTLA4--Ig results in functional and histomorphometric recovery that is superior to that seen in the absence of these medications.