Abstract
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)-1α, IL-1β, IL-6, tumour necrosis factor (TNF)-α, and TNF-β 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-1α, IL-6, and TNF-α mRNA in monocytes-macrophages infiltrating the glomeruli and interstitium. Occasionally, there was weak or moderate immunostaining for IL-1α, IL-6, and TNF-α 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.
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References
Atkins R, Glasgow E, Holdworth S, Matthews F (1976) The macrophage in human rapidly progressive glomerulonephritis. Lancet 1: 830–832
Baud L, Fouqueray B, Philippe C, Amrani A (1992) Tumor necrosis factor alpha and mesangial cells. Kidney Int 41: 600–603
Boswell J, Yui M, Burt D, Kelley V (1988a) Novel and enhanced interleukin 1 gene expression in autoimmune mice with lupus. J Immunol 141: 118–124
Boswell J, Yui M, Burt D, Kelley V (1988b) Increased tumor necrosis factor and IL-1β gene expression in the kidneys of mice with lupus nephritis. J Immunol 141: 3050–3054
Coleman D, Ruef C (1992) Interleukin-6: An autocrine regulator of the mesangial cell growth. Kidney Int 41: 604–606
Diamond J, Pesek I (1991) Glomerular tumor necrosis factor and interleukin 1 during acute aminonucleoside nephrosis. An immunohischemical study. Lab Invest 64 21–28
Diamond J, Ding G, Frye J, Diamond I-P (1992) Glomerular macrophages and the mesangial proliferative response in the experimental nephrotic syndrome. Am J Pathol 141: 887–894
Dinarello C (1989) Interleukin-1 and biologically related cytokines. Adv Immunol 44: 153–205
Ferrario F, Castiglione A, Colasanti G, di Belgioso G, Bertoli S, D'Amico G (1985) The detection of monocytes in human glomerulonephritis. Kidney Int 28: 513–519
Fukatsu A, Matsuo S, Tamai H, Sakamoto N, Matsuda T, Hirano T (1991) Distribution of interleukin-6 in normal and diseased human kidney. Lab Invest 65: 65–66
Horii Y, Muraguchi, Iwano M, Matsuda T, Hirayama Y, Yamada H, Fujii Y, Dohi K, Ishikawa H, Ohmoto Y, Yoshizaki K, Hirano T, Kishimoto T (1987) Involvement of IL-6 in mesangial proliferative glomerulonephritis. J Immunol 143: 3949–3955
Main IW, Nikolic-Paterson DJ, Atkins RC (1992) T cells and macrophages and their role in renal injury. Semin Nephrol 12: 395–407
Noronh I, Kruger C, Andrassy K, Ritz E, Waldherr R, (1993) In situ production of TNF-α, IL-1β and IL-2R in ANCA-positive glomerulonephritis. Kidney Int 43: 682–692
Sedor J R, Nakazato Y, Konieczkowski M. (1992) Interleukin-1 and the mesangial cell. Kidney Int 41: 595–599
Takemura T, Yoshioka K, Akano N, Miyamoto H, Matsumono K, Maki S (1987) Glomerular deposition of cross-linked fibrin in human kidney diseases. Kidney Int 32: 102–111
Terenghi G, Polak J (1992) Use of comparative in situ hybridization and immunohistochemistry for the study of reguratory peptides. In: Coulton G, De Belleroche J (eds) In situ hybridization: Medical applications. Academic Publishers, Boston, pp 37–51
Tipping P, Leong TW, Holdworth SR (1991a) Tumor necrosis factor production by glomerular macrophage in anti-glomerular basement membrane glomerulonephritis in rabbits. Lab Invest 65: 272–279
Tipping P, Lowe M, Holdworth SR (1991b) Glomerular interleukin 1 production is dependent on macrophage infiltration in anti-GBM glomerulonephritis. Kidney Int 39: 103–110
Waldherr R, Noronha I, Niemir Z, Kruger C, Stein H, Stumm G (1993) Expression of cytokines and growth factors in human glomerulonephritis. Pediatr Nephrol 7: 471–478
Weber H, Emancipator S, Tykocinski M, Sedor J (1987) The interleukin 1 gene is expressed by rat glomerular mesangial cells and is augmented in immune complex glomerulonephritis. J Immunol 138: 3207–3212
Wilson C (1991) The renal response to immunologic injury. In: Brenner B, Rector F (eds) The Kidney. W. B. Saunders, Philadelphia pp 1062–1181
Yoshioka K, Takemura T, Aya N., H M, Maki S (1989) Monocyte infiltration and cross-linked fibrin deposition in IgA nephritis and Henoch-Schoenlein purpura nephritis. Clin nephrol 32: 107–112
Yoshioka K, Takemura T, Murakami K, Aya N, Hino S, Miyazato H, Akano N, Maki S (1993a) Transforming growth factor-β protein and mRNA in glomeruli in normal and diseased human kidneys. Lab Invest 68: 154–163
Yoshioka K, Takemura T, Murakami K, Okada M, Yagi K, Miyazato H, Matsushima K, Maki S (1993b) In situ expression of cytokines in IgA nephritis. Kidney Int 44: 825–833
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Takemura, T., Yoshioka, K., Murakami, K. et al. Cellular localization of inflammatory cytokines in human glomerulonephritis. Vichows Archiv A Pathol Anat 424, 459–464 (1994). https://doi.org/10.1007/BF00191429
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DOI: https://doi.org/10.1007/BF00191429