We evaluated the expression of inflammatory cytokines in renal tissues obtained from 45 patients with several types of glomerulonephritis. Immunofluorescence studies with specific antibodies to interleukin (IL)-1 alpha, IL-1 beta, IL-6, tumour necrosis factor (TNF)-alpha, and TNF-beta showed intense cytoplasmic staining in the glomeruli and interstitium. Cells positive for these cytokines were found frequently in tissue from patients with lupus nephritis (WHO Class IV) and membranoproliferative glomerulonephritis, and, to a lesser extent, in tissue from patients with mesangial proliferative glomerulonephritis, Henoch-Schönlein purpura nephritis, and minimal change nephrotic syndrome. Most of these cells were dual-stained with a monoclonal antibody to monocytes-macrophages. In situ hybridization for cytokine mRNA, combined with immunoperoxidase staining for monocytes-macrophages, detected IL-1 alpha, IL-6, and TNF-alpha mRNA in monocytes-macrophages infiltrating the glomeruli and interstitium. Occasionally, there was weak or moderate immunostaining for IL-1 alpha, IL-6, and TNF-alpha in the glomerular mesangial and epithelial cells, but in situ hybridization signals were rarely found in these loci. These findings suggest that infiltrating monocytes-macrophages, rather than resident glomerular cells, are the major source of inflammatory cytokines in human glomerulonephritis.

Results. The primary analysis was conducted on 99 mizori-A multicenter trial of mizoribine compared with placebo in bine-and 98 placebo-treated patients. The relapse rate was children with frequently relapsing nephrotic syndrome.lower in the mizoribine group than in the placebo group (0.0055 Background. The use of corticosteroids or cytotoxic/immuvs. 0.0067; ratio 0.81, 95% CI, 0.61 to 1.05, P ϭ 0.12). The nosuppressive agents such as cyclophosphamide, chlorambucil, hazard ratio of the cumulative remission rate between the two and cyclosporine for the treatment of frequently relapsing negroups was 0.79 (95% CI, 0.57 to 1.08). In the subgroups conphrotic syndrome (FRNS) is limited because of their adverse sisting of patients 10 years old or younger, the relapse rate effects. This study was conducted to evaluate the efficacy and ratio between the mizoribine subgroup (54 patients) and the safety of mizoribine, a relatively new immunosuppressive drug placebo subgroup (57 patients) was 0.66 (95% CI, 0.44 to 0.94, developed in Japan, in children with FRNS.P ϭ 0.017). The hazard ratio of the cumulative remission rate Methods. A double-blind, placebo-controlled, multicenter between the two subgroups was 0.56 (95% CI, 0.37 to 0.85, trial was carried out in children, from 2 to 19 years old, with P ϭ 0.007). Hyperuricemia was the most common adverse FRNS. At relapse, patients were treated with prednisolone. event with mizoribine (16%), but was transient. According to a dynamic allocation, mizoribine or a placebo Conclusions. Compared with the placebo, mizoribine significantly decreased the relapse rate and prolonged the remission was concurrently administered to each patient. Prednisolone period in the subgroup consisting of patients 10 years old or was gradually tapered and discontinued within 12 weeks. The younger. This drug may be useful in young children with FRNS test drug was maintained for 48 weeks. The primary end point who generally relapse more frequently than older children. was the relapse rate (the total number of relapses/the total treatment days for all patients). Analyses were performed according to the intention-to-treat principle.