FK506 treatment in a Long-term chronic rejection rat model of small bowel transplantation.

BACKGROUND Although acute rejection (AR) can be significantly improved by effective immunosuppressants, such as FK506, chronic rejection (CR) remains a major hurdle to long-term allograft survival after small bowel transplantation, in part because the pathogenic mechanisms of CR are, as yet, unknown. The rat orthotopic small bowel transplantation (OSBT) model has been used by a few researchers, but without long-term survival. METHODS Rats were randomly divided into five groups: Group 1 (n=20), sham-operation rats; Group 2 (n=20), Lewis to Lewis; Group 3 (n=20), F344 to Lewis treated with FK506 (0.3 mg/kg/day); Group 4 (n=20), F344 to Lewis with FK506 (0.5 mg/kg/day); Group 5 (n=20), F344 to Lewis with FK506 (1.0 mg/kg/day). FK506 was administrated intramuscularly to recipients on postoperative days (POD) 0-13, 20 and 27. Body weight, survival rate and histology were measured. RESULTS Histopathological analysis revealed distinctive abnormalities of the allograft for all animals, including changes in villous architecture, interstitial fibrosis and intimal thickening; however, survival times were significantly increased with higher doses of FK506. Rats in Group 3 and Group 4 (low and moderate FK506 doses) survived 16-18 weeks, while recipients in Group 5 (high dose) survived 24-27 weeks. CONCLUSION FK506 treatment (1.0 mg/kg/day, intramuscularly administrated to recipients on POD0-13, 20 and 27) can be used effectively to establish a rat OBST model of CR that will be useful for the study of the pathogenesis of CR and the effectiveness of various drugs.