A Preliminary Study On Diagnosis And Forecast Of Immune Tolerance In Rat Recipients After Allogeneic Liver Transplantation

Part oneInducement immune tolerance in rat recipients after allogeneic livertransplantationOrgan transplantation is the treatment of choice for patients with end-stage organ failure. Inducing persistent immune tolerance and controlling acute rejection and improving the ratio of long term survival of organ transplantational recipients are crucial problems. Liver is immune privilege organ. Clinical research have presented documents that clinical immune tolerance exists in liver transplantational recipients off immunosuppressor. The goals of this study was to analyze the possibility and effective methods of inducement immune tolerance with Cyclosporine in rat orthotopic liver transplantational (OLT) recipients.Materials and MethodsInbred male Lewis rats (RT1~1) were used as allogeneic donors and BN rats(RT1~n) were used as syngeneic and allogeneic recipients. All recipients were divided as follows: Group A: Syngeneic control (BN-to-BN) without any treatment; Group B: Acute rejection (LEW-to-BN) without any treatment; Group C: Acute rejection treated with lower dosage ofCsA 1 .Omg/kg/day from day 1-5 (LEW-to-BN+ CsA).Group D: Acute rejection treated with middle dosage of CsA 1.5mg/kg/day from day 1-5 (LEW-to-BN + CsA) Group E: Acute rejection treated with larger dosage of CsA 2.0mg/kg/day from day 1-5 (LEW-to-BN + CsA); Group F:Acute rejection treated with prolonged middle dosage of CsA 1.5mg/kg/day from day 1-7 (LEW-to-BN + CsA). All groups were subdivided into day 5, 7, 9 (n=3 each) post-transplantation respectively for harvesting peripheral blood and all animals did not killed and bred for observation of general situation and survival time. Serum were harvested at indicated time to determine the levels of IL-2 and IFN-yby ELISA.ResultsAll syngeneic liver transplants in group A survived more than 100 days, recipients in group B(LEW-to-BN without CsA) had a median survival time of 35 days. 1/9 recipients in group C (LEW-to-BN with lower dosage of CsA), 2/9 recipients in group D (LEW-to-BN with middle dosage of CsA), 0/9 recipients in group E (LEW-to-BN with larger dosage of CsA), and 5/9 recipients in group F (LEW-to-BN with prolonged middle dosage of CsA) survived more than 100 days. The pathological changes of liver grafts in died recipients off CsA was the same as acute rejection grafts in group B. After OLT, in group B, the level of serum IL-2 and IFN-y was the highest on day 7,then descended on day 9. Treated with CsA the level of serum IL-2 and IFN-yin group C,D,E,F was suppressed, nevertheless, it was rebounded off CsA. There was significant difference in group E (LEW-to-BN with larger dosage of CsA)(P<0.01), but there was no significant difference in group F (LEW-to-BN with prolonged middle dosage of CsA)(P>0.05).DiscussionIn this study, all recipients in group E (acute rejection with larger dosage of CsA) died off CsA, and their median survival time is shorter than in group B (acute rejection without CsA). Meanwhile, treatment with lower and middle dosage CsA, 1/9 and 2/9 got long time survival, prolonged treatment of CsA, the ratio of long time survival also rose in group F. This studyindicated prolonging the time of treatment with CsA in middle or lower dosage may rise the ratio of immune tolerance in rat liver transplantational recipients.After stoped short term treatment of CsA, the biomarker of acute rejection, serum level of IL-2 and IFN-γ, was higher than using CsA. It was the highest in the group with larger dosage of CsA, and the least in the group with lower dosage of CsA. It indicated if patients need to withdraw immunosuppressor, lower dosage of immunosuppressor is safer than larger dosage.Conclusions1. A short course of lower dosage of CsA can induce tolerance of rat liver allografts in acute rejection combination (LEW-BN).2. Withdrawing CsA should be performed when patients take lower dosage of CsA, otherwise, if patients are taking larger dosage of CsA, withdrawing CsA suddenly would result in allogeneic liver graft accelerated re...