LOCAL IMMUNOSUPPRESSION WITH BUDESONIDE AFTER LIVER-TRANSPLANTATION IN THE RAT - A PRELIMINARY HISTOMORPHOLOGICAL ANALYSIS

Background. In this study we have analyzed the local immunosuppression with budesonide, a topically selective glucocorticosteroid, in rats a fter orthotopic liver transplantation. Because of its high first-pass hepatic clearance budesonide can be given orally, achieving high intra hepatic and low systemic concentrations. Methods. Using an acute rejec tion model from Dark Agouti (DA) to Lewis rats, the histomorphological degree of rejection was assessed on histological sections at the nint h postoperative day. Results. Livers of the DA to Lewis study group wi thout immunosuppression revealed severe allograft rejection with vast cellular infiltrates, massive endothelialitis, and hepatocyte necrosis . In the three budesonide study groups (250 mu g, 500 mu g, and 1 mg/k g/day) a moderate to mild liver allograft rejection was seen. Rejectio n was most prominent in the 250 mu g group, whereas the 1 g group show ed almost no signs of rejection, similar to the Lewis to Lewis control group. Aspartate and alanine transaminase (sGOT, sGPT) as well as alk aline phosphatase serum levels correlated with the degree of rejection , achieving highest levels in the DA to Lewis group without immunosupp ression. Animals treated with 1 g of budesonide had serum levels simil ar to Lewis to Lewis control animals. Conclusions. These results impli cate a beneficial effect of local immunosuppression with budesonide in rats based on the histomorphological degree of liver allograft reject ion.