Application of Microsphere Including Taclorimus-FK506 to Immunosuppression for Small Bowel Transplantation

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Rejection remains a major barrier to successful bowel transplantation, despite improved immunosuppressive techniques. New immunosuppressant which has more effect and less side effect is needed. New biodegeneradable microsphere containing Tacrolimus (FK506) was applied to experimental porcine whole small bowel transplantation in which allogenesity between donors and recipients were confirmed by mixed lymphocyte reaction. After transplantation, endoscopic biopsy for histology every 3 days and Tacrolimus (TAC) blood level test daily were performed. Study groups consisted of TAC-0.5mg/kg, TAC-0.2mg/kg, microsphere containing TAC(MS-TAC)0.5mg/kg, MS-TAC0.1mg/kg, MS-TAC0.4mg/kg and MS-TAC0.02mg/kg. Survival period was 9.7, 11.0, 12. 7. 5. 28.6 9.5 days, respectively. TAC trough level was 27.9, 10.9, 60.6, 40.3, 24.6, 10.5, 9.5 ng/ml, respectively. All animals with merely TAC had rejection and 40% of TAC0.5mg/kg had infection. All of MS-TAC0.1, 0.5, 1.0 had no rejection but had infection. Non of MS-TAC0.04 had rejection and infection. Half of MS-TAC0.02 had rejection but not infection. MS-TAC0.04 achieved longer survival and less side effects in this model. MS-TAC has a great potency in immunosuppression with less side effects for small bowel transplantation.