A short course of methylprednisolone immunosuppression inhibits both rejection and spontaneous acceptance of rat liver allografts

Background The effects of immunosuppressive drugs on transplant tolerance h ave not been extensively studied, although their effect on rejection is wel l established. Methods. We examined the effects of a short course of treatment with the im munosuppressive drug methylprednisolone (MP) on the survival of PVG; liver allografts in Dark Agouti (DA) recipients that accepted the livers and in L ewis recipients that rejected the livers. Infiltration of liver allografts was examined by immunohistochemical staining of liver sections, and apoptos is was measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling. Results. A S-day course of MP (days 0 to 4) led to rejection of four of six livers (mean survival time [MST] 99 days) in DA recipients compared with l ongterm survival (MST >100 days) in untreated animals. Delayed administrati on of MP (days 3 to 7) exacerbated rejection in DA recipients, and all eigh t animals rejected the graft (MST 68.5 days). Treatment of Lewis recipients with MP did not significantly prolong survival when administered from days 0 to 4 (MST 13 days), although delay of administration improved the outcom e. Treatment from days 3 to 7 resulted in an MST of 21 days, whereas treatm ent from days 7 to 11 resulted in an MST of 41.5 days. MP treatment from da y 3 to day 7 reduced T cells and interleukin 2 receptor-expressing cells bu t increased the numbers of apoptotic cells infiltrating both DA and Lewis s train allografts. Conclusions. These results show that immunosuppression with MP inhibits bot h spontaneous tolerance and rejection of liver allografts in a rat model an d question the efficacy of administering MP to all liver allograft recipien ts from the time of transplantation.