Attenuation of immune complex nephritis in NZB/WF1 mice by a prostacyclin analogue.
Although prostaglandins have been shown to inhibit the evolution of the nephritis in NZB/W mice, the mechanisms of this effect are unknown. To characterize such inhibition, we injected the prostacyclin (PGI2) 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 the mice were 2 months old. Evaluation included measurement of urine albumin excretion, serological parameters and splenic T cell subset, as well as examination of renal histology by light and fluorescence microscopy. Mice given beraprost showed a marked decrease in urine albumin excretion and in glomerular hypercellularity compared with untreated controls. Maximal beneficial effects occurred when the dose was 5.0 mg/kg of beraprost. These effects correlated with a reduction of immune complex deposition in glomeruli. In addition, beraprost reduced serum levels of immunoglobulins and anti-double-stranded DNA antibodies, and decreased 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 autoantibodies and deposition of immune complexes in glomeruli.
Utsunomiya
Y
Y
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Ogura
M
M
Kawamura
T
T
Mitarai
T
T
Maruyama
N
N
Sakai
O
O
D000419:Albuminuria / Q000517:prevention & control; D000818:Animals; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D007105:Immune Complex Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005779:Immunodiffusion / Q000379:methods; D007668:Kidney / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D009393:Nephritis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
C048081:beraprost; D011464:Epoprostenol