Effective methylprednisolone dose in experimental crescentic glomerulonephritis.
Pulse methylprednisolone (MP) therapy improves the prognosis of crescentic glomerulonephritis, but the optimal dose is uncertain. We reported previously that treatment with MP at a dose of 30 mg/kg reduces glomerular crescents and infiltrating mononuclear cells and ameliorates the clinical abnormalities in an animal model of crescentic glomerulonephritis. In the present study, we assessed MP dose requirement for these beneficial effects in correlation with the effect on gene expression of chemokines, potential molecules responsible for recruitment and activation of leukocytes. Animals were treated with MP, 5 to 30 mg/kg/d, for 4 consecutive days after cellular crescents had been formed diffusely. The level of crescents and numbers of glomerular and interstitial monocytes/macrophages and T lymphocytes were reduced significantly by 5 mg/kg of MP, but maximal effect was obtained by 30 mg/kg of MP. Urinary protein was reduced significantly in a 30-mg/kg group but not in other groups. The gene expression of chemokines, MCP-1, MCP-3, TCA3, MIP-1alpha, MIP-1ss, RANTES, and lymphotactin, was enhanced in this model and was inhibited strongly by 5 mg/kg of MP. These results indicate that MP reduces the number of infiltrating mononuclear cells and crescents in the rat model in a dose-dependent fashion and that, despite the strong inhibition of chemokine expression at a lower dose, the beneficial effect of MP is maximal at a dose of 30 mg/kg.
Ou
Z L
ZL
Research Institute, International Medical Center of Japan, Tokyo, Japan.
Nakayama
K
K
Natori
Y
Y
Doi
N
N
Saito
T
T
Natori
Y
Y
D000818:Animals; D018925:Chemokines / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000209:etiology; D005938:Glucocorticoids / Q000008:administration & dosage*; D007678:Kidney Glomerulus / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes; D008775:Methylprednisolone / Q000008:administration & dosage*; D011507:Proteinuria; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018925:Chemokines; D005938:Glucocorticoids; D012333:RNA, Messenger; D008775:Methylprednisolone