K YOSHIOKA; T TAKEMURA; K MURAKAMI; M OKADA; K YAGI; H MIYAZATO; K MATSUSHIMA; S MAKI
KIDNEY INTERNATIONAL 44 4 825 - 833 1993年10月
[査読有り] We studied mRNA and protein expression of interleukins (IL) and tumor necrosis factor (TNF) in renal tissues biopsied from 40 patients with IgA nephritis. Immunofluorescent staining with antibodies to IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha, and TNF-beta was intense in the cytoplasm of cells in glomeruli, which were dual-stained with an anti-monocyte-macrophage antibody. In addition, moderate immunofluorescence for TNF-alpha, and weak staining for IL-1alpha and IL-6 were occasionally found in resident glomerular cells. Immunoperoxidase-in situ hybridization dual-labeling revealed that IL-1alpha, IL-6, and TNF-alpha mRNA signals were present in intraglomerular cells reactive with anti-monocyte-macrophage antibody, which further supported the immunofluorescent findings. Cells expressing IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha, and TNF-beta were also observed in the interstitium. Most of these cells were also labeled with the anti-monocyte-macrophage antibody. The number of IL-1alpha, IL-6, and TNF-alpha-positive cells infiltrating the glomerulus significantly correlated with mesangial hypercellularity. IL-8 and TNF-alpha-positive intraglomerular cells were correlated with the magnitude of proteinuria. The population of interstitial cells positive for IL-1alpha, IL-6, IL-8, and TNF-alpha was associated with the grade of tubulointerstitial changes and proteinuria. There was no correlation between local IL-1alpha, IL-6, and TNF-alpha expression in glomeruli or interstitium and serum or urinary levels of the respective cytokines. These results indicate that several cytokines were simultaneously expressed by infiltrating monocyte/macrophages and, to a lesser extent by resident glomerular cells, and that IL-1alpha, IL-6, and TNF-alpha may be important as promoters of mesangial proliferation in human IgA nephritis.