TREATMENT WITH FK506 PREVENTS REJECTION OF RAT COLON ALLOGRAFTS

Colon transplantation has been proposed as a method to improve the fun ction of an intestinal allograft. The present study examined the risk of colon rejection and the effect of FK506 on colon rejection in BN -- > LEW rats with orthotopic bowel transplants. The first 4 groups inclu ded rats with untreated allografts (group 1), rats with isografts trea ted with 0.6 mg/kg FK506 (group 2), rats with allografts treated with 0.6 mg/kg FK506 (group S), and rats with allografts treated with 0.4 m g/kg FK506 (group 4). In each of these groups (10-12 rats), half of th e animals received a small bowel graft only (SB), while the other half received a small bowel, ascending colon, and cecum graft (SBC). The a nimals were followed daily until they died or were killed at 4 weeks. In group 5, an additional 18 untreated rats with SBC allografts were r andomly killed on the third, fifth, seventh, and tenth postoperative d ays to study the sequential histo pathologic and immunopathologic chan ges of colon rejection. There was no difference in survival, body weig ht, nutritional parameters, or bacterial contamination after SB and SB C transplantation. Intestinal transit was slower after SBC than SB tra nsplantation (P<0.05). Sequential histopathologic studies revealed tha t (1) the severity and time course of colon rejection was similar to s mall intestine rejection, and (2) the features of colon rejection were similar to ulcerative colitis. There was no evidence of graft-versus- host disease after SBC transplantation. In summary, adding a segment o f large bowel to a small bowel allograft does not increase the risk of rejection or surgical complications. The transplanted colon slows int estinal transit. Treatment with FK506 effectively prevents colon rejec tion. These data suggest that adding a colon graft may improve the out come of clinical small bowel transplantation.