MARKED ANTINEPHRITIC ACTION AND LESS ADVERSE-EFFECTS OF METHYLPREDNISOLONE SULEPTANATE BY INTERMITTENT ADMINISTRATION IN RATS

To establish the regimen for beneficial prolonged treatment with gluco corticoids on nephritis, we investigated the antinephritic effect of m ethylprednisolone suleptanate (MPS) and its influence on adrenal funct ion by intermittent administration (IA) in comparison with daily admin istration (DA) in crescentic-type anti-GBM nephritic rats. In IA, MPS (0.25, 1.0 and 3.0 mg/kg) was injected for 3 successive days followed by a 3-day withdrawal during a 40-day period. MPS inhibited the elevat ion of urinary protein and serum cholesterol and glomerular alteration s by both IA and DA. The effect of MPS on these parameters was more po tent by IA than by DA. MPS significantly suppressed the increment of t he number of ED-1(+) cells and TH-1(+) cells in nephritic glomeruli. D A, but not IA, caused atrophy of the adrenal glands. IA prevented the remarkable decrease in corticosterone level provoked in nephritic rats . In conclusion, for the treatment of nephritis, IA seems to be a bett er regimen for the administration of MPS. MPS may exert an antinephrit ic action by inhibiting mesangial cell proliferation and infiltration of monocytes/macrophages into glomeruli in addition inhibiting antibod y production.