The immunosuppressive effects of a leukotriene B4 receptor antagonist on liver allotransplantation in rats.

The immunosuppressive effects of a leukotriene B4 (LTB4) receptor antagonist, ONO4057, on liver allotransplantation in rats were evaluated, and the levels of prostaglandin E2 (PGE2) in the liver tissue during rejection of the allografts examined. The rats were divided into four groups: group 1: Lewis rats (LEW) given a sham operation with dimethyl sulfoxide (DMSO); group 2: LEW given syngenic orthotopic liver transplantation (OLT) from LEW, with DMSO; group 3: LEW given allogenic OLT from ACI rats (ACI), with DMSO; and group 4: LEW given allogenic OLT from ACI, with ONO4057 as 10, 30, or 100 mg/kg per day dissolved in DMSO to subgroups 4a, 4b, and 4c, respectively. Histological examinations were performed, survival times monitored, and liver tissue PGE2 levels 3, 5, 7, and 14 days after transplantation measured. The mean graft survival times in groups 4a, b, and c, at 37.5 +/- 10.4, 52.2 +/- 24.4, and 34.0 +/- 4.9 days (mean +/- SEM), respectively, were significantly longer than that in group 3 (at 13.0 +/- 3.2 days). Moreover, the levels of tissue PGE2 in the liver allografts in group 4a were significantly higher than those in group 3 on days 5 and 7. These results suggest that ONO4057 has an immunosuppressive effect on liver allotransplantation since it reduces the activities of LTB4 which augments immune responses, and also because it indirectly increases the PGE2 level.