Virchows Archiv

, Volume 424, Issue 5, pp 459–464 | Cite as

Cellular localization of inflammatory cytokines in human glomerulonephritis

  • T. Takemura
  • K. Yoshioka
  • K. Murakami
  • N. Akano
  • M. Okada
  • N. Aya
  • S. Maki
Original Article

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.

Key words

Interleukin Tumour necrosis factor Glomerulonephritis Monocytes Macrophages 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Atkins R, Glasgow E, Holdworth S, Matthews F (1976) The macrophage in human rapidly progressive glomerulonephritis. Lancet 1: 830–832Google Scholar
  2. 2.
    Baud L, Fouqueray B, Philippe C, Amrani A (1992) Tumor necrosis factor alpha and mesangial cells. Kidney Int 41: 600–603Google Scholar
  3. 3.
    Boswell J, Yui M, Burt D, Kelley V (1988a) Novel and enhanced interleukin 1 gene expression in autoimmune mice with lupus. J Immunol 141: 118–124Google Scholar
  4. 4.
    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: 3050–3054Google Scholar
  5. 5.
    Coleman D, Ruef C (1992) Interleukin-6: An autocrine regulator of the mesangial cell growth. Kidney Int 41: 604–606Google Scholar
  6. 6.
    Diamond J, Pesek I (1991) Glomerular tumor necrosis factor and interleukin 1 during acute aminonucleoside nephrosis. An immunohischemical study. Lab Invest 64 21–28Google Scholar
  7. 7.
    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: 887–894Google Scholar
  8. 8.
    Dinarello C (1989) Interleukin-1 and biologically related cytokines. Adv Immunol 44: 153–205Google Scholar
  9. 9.
    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: 513–519Google Scholar
  10. 10.
    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: 65–66Google Scholar
  11. 11.
    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: 3949–3955Google Scholar
  12. 12.
    Main IW, Nikolic-Paterson DJ, Atkins RC (1992) T cells and macrophages and their role in renal injury. Semin Nephrol 12: 395–407Google Scholar
  13. 13.
    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: 682–692Google Scholar
  14. 14.
    Sedor J R, Nakazato Y, Konieczkowski M. (1992) Interleukin-1 and the mesangial cell. Kidney Int 41: 595–599Google Scholar
  15. 15.
    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: 102–111Google Scholar
  16. 16.
    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 37–51Google Scholar
  17. 17.
    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: 272–279Google Scholar
  18. 18.
    Tipping P, Lowe M, Holdworth SR (1991b) Glomerular interleukin 1 production is dependent on macrophage infiltration in anti-GBM glomerulonephritis. Kidney Int 39: 103–110Google Scholar
  19. 19.
    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: 471–478Google Scholar
  20. 20.
    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: 3207–3212Google Scholar
  21. 21.
    Wilson C (1991) The renal response to immunologic injury. In: Brenner B, Rector F (eds) The Kidney. W. B. Saunders, Philadelphia pp 1062–1181Google Scholar
  22. 22.
    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: 107–112Google Scholar
  23. 23.
    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: 154–163Google Scholar
  24. 24.
    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: 825–833Google Scholar

Copyright information

© Springer Verlag 1994

Authors and Affiliations

  • T. Takemura
    • 1
  • K. Yoshioka
    • 1
  • K. Murakami
    • 1
  • N. Akano
    • 1
  • M. Okada
    • 1
  • N. Aya
    • 1
  • S. Maki
    • 1
  1. 1.Department of PediatricsKinki University School of MedicineOsaka-sayamaJapan

Personalised recommendations