Therapeutic effect of glucocorticoid on experimental crescentic glomerulonephritis.
Crescentic glomerulonephritis shows active and progressive glomerular changes with rapid deterioration in kidney function. A large dose of glucocorticoid (pulse therapy) is clinically used for the treatment, but its efficacy has not been fully estimated. In this study we assessed the therapeutic effect of a large dose of methyl-prednisolone (MP) on a rat model of crescentic glomerulonephritis that had been induced in WKY rats by an injection of anti-glomerular basement membrane antibody. The infiltration of CD8+ cells and monocytes was manifest by day 3, proteinuria appeared on days 4 and 5, and cellular crescents were diffusely formed by day 7. The gene expression of MCP-1, a chemokine for monocytes and T lymphocytes, was enhanced within 4 hours and peaked on day 3. Daily administration of MP (30 mg/kg/d) from day 3 through day 6 reduced the gene expression of MCP-1 and the numbers of glomerular leukocytes and largely prevented both crescent formation and proteinuria. When daily MP treatment started on day 7, the numbers of glomerular CD8+ cells and monocytes, crescents, and urinary protein were significantly reduced by day 11. In addition, continuing treatment with a small dose of MP (3 mg/kg/d) begun on day 11 completely prevented the increase in blood urea nitrogen and serum creatinine levels. These results indicate that treatment with a large dose of MP histologically and clinically ameliorates crescentic glomerulonephritis in a rat model, supporting the efficacy of pulse MP therapy for the treatment of the disease in human subjects.
Yamamoto-Shuda
Y
Y
Research Institute, International Medical Center of Japan, Tokyo.
Nakayama
K
K
Saito
T
T
Natori
Y
Y
D000818:Animals; D001806:Blood Urea Nitrogen; D015152:Blotting, Northern; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology; D007958:Leukocyte Count; D008775:Methylprednisolone / Q000494:pharmacology*; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D020551:Pulse Therapy, Drug; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY
D018932:Chemokine CCL2; D005938:Glucocorticoids; D012333:RNA, Messenger; D003404:Creatinine; D008775:Methylprednisolone