Therapeutic effects of leflunomide, a new antirheumatic drug, on glomerulonephritis induced by the antibasement membrane antibody in rats

Abstract

Leflunomide is a new antirheumatic drug. It was evaluated, in comparison with azathioprine (AZA) and methylprednisolone acetate (MPA), for its therapeutic effects on the glomerulonephritis induced in rats by rabbit antiserum against the rat glomerular basement membrane. Its effect on body weight was also determined. Leflunomide (2 and 10 mg/kg/day, po), AZA (20 mg/kg/day, po), and MPA (2 mg/kg/day, sc) were administered for 28 days from 5 days after the intravenous injection of the rabbit antiserum. Leflunomide at both doses significantly decreased the urinary total protein, plasma total cholesterol, and plasma fibrinogen. On the other hand, neither AZA nor MPA affected the parameters except that they tended to reduce the urinary total protein. All three compounds decreased the plasma rat anti-rabbit IgG titer. Histologically, leflunomide at the high dose showed apparent therapeutic effects on the glomerulonephritis, as judged by light and electron microscopy and by immunofluorescence; the lesions were improved and deposits of rat IgG and C3 along the glomerular capillary wall decreased to a great extent. AZA and MPA exerted no therapeutic effects on the histological parameters except that MPA tended to reduce rat IgG and C3 deposits. Body weights increased favorably and slightly during leflunomide and AZA administration, respectively, but decreased during MPA treatment. Thus, leflunomide had more potent therapeutic effects on glomerulonephritis and less side effects than the already marketed drugs, suggesting that the compound is highly effective in improving immunologically mediated forms of glomerulonephritis, including membranous glomerulonephritis, at their early stages.