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Interleukin-1 receptor antagonist ameliorates experimental antiglomerular basement-membrane antibody-associated glomerulonephritis

Academic Article
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Overview

authors

  • Tang, W. W.
  • Feng, L.
  • Vannice, J. L.
  • Wilson, Curtis

publication date

  • January 1994

journal

  • Journal of Clinical Investigation  Journal

abstract

  • The contribution of IL-1 to leukocyte infiltration in anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was examined by the administration of a specific IL-1 receptor antagonist (IL-1ra). Lewis rats received anti-GBM Ab or normal rabbit serum and were treated with either 0.9% saline or 6 mg IL-1ra over a 24-h time period. Plasma IL-1ra concentration was 2,659 +/- 51 ng/ml 4 h after anti-GBM Ab and IL-1ra administration. PMN and monocyte/macrophage infiltration declined 39% (9.8 +/- 1.9 to 6.0 +/- 1.5 PMN/glomerulus, P < 0.001) and 29% (4.9 +/- 0.8 to 3.5 +/- 0.8 ED-1 cells/glomerulus, P = 0.002) with IL-1ra treatment at 4 h, respectively. Similarly, the number of glomerular cells staining for lymphocyte function-associated molecule-1 beta (CD18) declined 39% from 16.7 +/- 1.9 to 10.7 +/- 1.6 cells/glomerulus at 4 h (P = 0.0001). This was associated with a decrease in glomerular intracellular adhesion molecule-1 expression. The mean glomerular intracellular adhesion molecule-1 score in anti-GBM Ab GN rats treated with IL-1ra was less than that of rats administered anti-GBM Ab and 0.9% saline at 4 (2.0 +/- 0.2 vs 2.5 +/- 0.2, P < 0.05) and 24 (2.5 +/- 0.1 vs 3.1 +/- 0.2, P = 0.0001) h. These immunopathologic changes correlated with a 50% reduction in proteinuria from 147 +/- 34 to 75 +/- 25 mg/d (P < 0.002). Treatment with IL-1ra did not affect the steady state mRNA expression of either IL-1 beta or TNF alpha. An increase in the IL-1ra dose to 30 mg given within the initial 4 h provided no additional benefit. The decline in PMN and monocyte/macrophage infiltration of the glomerulus at 4 h was similar to that found in the initial study. Furthermore, the protective benefit of IL-1ra was abrogated by doubling the dose of the anti-GBM Ab GN, despite administering high dose IL-1ra (30 mg). In these studies, detectable IL-1ra was found in the serum of untreated anti-GBM Ab GN controls. These data suggest a positive yet limited role for IL-1ra in the therapeutic intervention of anti-GBM Ab GN.

subject areas

  • Animals
  • Antibodies
  • Basement Membrane
  • Cell Adhesion Molecules
  • Female
  • Glomerulonephritis
  • Inflammation
  • Intercellular Adhesion Molecule-1
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Kidney Glomerulus
  • Leukocytes
  • RNA, Messenger
  • Rats
  • Rats, Inbred Lew
  • Receptors, Interleukin-1
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
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Research

keywords

  • INTRACELLULAR ADHESION MOLECULE-1
  • LYMPHOCYTE FUNCTION-ASSOCIATED MOLECULE-1
  • MACROPHAGE
  • NEUTROPHIL
  • PROTEINURIA
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci116956

PubMed ID

  • 7904269
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Additional Document Info

start page

  • 273

end page

  • 279

volume

  • 93

issue

  • 1

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