ATTENUATION OF IMMUNE-COMPLEX NEPHRITIS IN NZB W F1-MICE BY A PROSTACYCLIN ANALOG/

Although prostaglandins have been shown to inhibit the evolution of th e nephritis in NZB/W mice, the mechanisms of this effect are unknown. To characterize such inhibition, we injected the prostacyclin (PGI(2)) analogue, beraprost, into NZB/W mice, using 0.5 mg, 1.0 mg or 5.0 mg beraprost/kg body weight of test animals three times in 1 week when th e mice were 2 months old. Evaluation included measurement of urine alb umin excretion, serological parameters and splenic T cell subset, as w ell as examination of renal histology by light and fluorescence micros copy. Mice given beraprost showed a marked decrease in urine albumin e xcretion and in glomerular hypercellularity compared with untreated co ntrols. Maximal beneficial effects occurred when the dose was 5.0 mg/k g of beraprost. These effects correlated with a reduction of immune co mplex deposition in glomeruli. In addition, beraprost reduced serum le vels of immunoglobulins and anti-double-stranded DNA antibodies, and d ecreased the number of helper (L3T4(+)) T cells in splenocytes. These results indicate that beraprost attenuates the nephritis of NZB/W mice , and that the source of this effect is the reduced production of auto antibodies and deposition of immune complexes in glomeruli.