In situ expression of cytokines in IgA nephritis

Abstract

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-1α, IL-1β, IL-6, IL-8, TNF-α, and TNF-β 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-α, and weak staining for IL-1α and IL-6 were occasionally found in resident glomerular cells. Immunoperoxidase-in situ hybridization dual-labeling revealed that IL-1α, IL-6, and TNF-α mRNA signals were present in intraglomerular cells reactive with anti-monocyte-macrophage antibody, which further supported the immunofluorescent findings. Cells expressing IL-1α, IL-1β, IL-6, IL-8, TNF-α, and TNF-β were also observed in the interstitium. Most of these cells were also labeled with the antimonocyte-macrophage antibody.The number of IL-1α, IL-6, and TNF-α-positive cells infiltrating the glomerulus significantly correlated with mesangial hypercellularity. IL-8 and TNF-α-positive intraglomerular cells were correlated with the magnitude of proteinuria. The population of interstitial cells positive for IL-1α, IL-6, IL-8, and TNF-α was associated with the grade of tubulointerstitial changes and proteinuria. There was no correlation between local IL-1α, IL-6, and TNF-α 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-1α, IL-6, and TNF-α may be important as promoters of mesangial proliferation in human IgA nephritis.