CELLULAR-LOCALIZATION OF INFLAMMATORY CYTOKINES IN HUMAN GLOMERULONEPHRITIS

We evaluated the expression of inflammatory cytokines in renal tissues obtained from 45 patients with several types of glomerulonephritis. I mmunofluorescence 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 interst itium. Cells positive for these cytokines were found frequently in tis sue from patients with lupus nephritis (WHO Class IV) and membranoprol iferative glomerulonephritis, and, to a lesser extent, in tissue from patients with mesangial proliferative glomerulonephritis, Henoch-Schon lein 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 i mmunoperoxidase staining for monocytes-macrophages, detected IL-1 alph a, IL-6 and TNF-alpha mRNA in monocytes-macrophages infiltrating the g lomeruli and interstitium. Occasionally, there was weak or moderate im munostaining for IL-1 alpha, IL-6, and TNF-alpha in the glomerular mes angial and epithelial cells, but in situ hybridization signals were ra rely found in these loci. These findings suggest that infiltrating mon ocytes-macrophages, rather than resident glomerular cells, are the maj or source of inflammatory cytokines in human glomerulonephritis.