We evaluated the effect of the novel immunosuppressive agent, FK506, which is known to inhibit T cell immunity, on the development of lupus nephritis in MRL/MpJ-lpr/lpr (MRL/l) mice. FK506 was administered subcutaneously (1 mg/kg body weight) from 12 to 20 weeks of age in 13 MRL/l mice with spontaneous lupus nephritis. Nine animals receiving no treatment were used as the control. FK506 significantly reduced the development of proteinuria, lowered the level of BUN, and suppressed the elevation of serum anti-dsDNA antibodies. Histopathological study showed that FK506 significantly inhibited the progression of glomerular hypercellularity and crescent formation. Glomerular deposition of C3 was significantly reduced in the FK506-treated mice compared to the nontreated controls. These findings suggest that FK506 may protect against progression of lupus nephritis in MRL/1 mice, an animal model of systemic lupus erythematosus.

Effect of the immunosuppressive agent, ciclosporin (CS), on bovine serum albumin (BSA) nephritis in rats was evaluated. Eight weeks after immunization, 19 male Wistar rats received a daily intravenous dose of BSA (2 mg). Two weeks later, 11 rats received BSA and an oral dose of CS (10 mg/kg), and 8 rats received only BSA for 2 weeks. Urinary protein was measured weekly and serum anti-BSA antibody was measured by passive hemagglutination biweekly. The animals were killed at the 12th experimental week and blood samples and kidney specimens were obtained. BUN and serum creatinine were measured at the time of sacrifice. Kidney specimens were processed for light and immunofluorescent microscopic examination. Urinary protein excretion was significantly less in CS-treated rats than in nontreated controls at the 2nd week after treatment (5.3 ± 1.3 vs. 25.6 ± 10.3 mg/day, p < 0.05). Anti-BSA antibody titers were lower in treated rats than in controls at the 2nd week after the treatment. There were no significant differences in the levels of BUN and serum creatinine between two groups. Glomerular hypercellularity and mesangial widening were milder in treated rats than in controls, and glomerular deposition of BSA was less intense in treated rats than in controls. These results suggest that CS suppressed the antibody production and the development of glomerular changes in rats with immune complex glomerulonephritis.

Platelet-activating factor (PAF) is known as an important mediator in the pathogenesis of glomerular injury. In the present study, we evaluated the effect of the specific PAF antagonists CV-6209 and CV-3988 on accelerated nephrotoxic serum nephritis (NTN) in the rat. The amount of urinary protein excretion was significantly less in the rats treated with CV-6209 or CV-3988 on the 5th and 7th day of treatment than in the nontreated controls. The results of light- and immunofluorescence-microscopic examination did not demonstrate any favorable effect on glomerular changes by these PAF antagonists. However, CV-6209 protected against the loss of glomerular anionic charges in rats with NTN. Thus, it is suggested that PAF is a potent mediator of protein excretion, and that the loss of glomerular anionic charges is an important mechanism for the mediation of PAF in glomerulonephritis.

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