Suppression of experimental crescentic glomerulonephritis by the interleukin-1 receptor antagonist

Kidney Int. 1993 Feb;43(2):479-85. doi: 10.1038/ki.1993.70.


The role of interleukin-1 (IL-1) in the pathogenesis of experimental crescentic glomerulonephritis was investigated. Administration of the interleukin-1 receptor antagonist (IL-1ra) was used to block the action of IL-1 during disease development. Two groups of six rats were primed with rabbit IgG, followed five days later by injection of rabbit anti-GBM serum (day 0). Animals were treated with a constant infusion of recombinant human IL-1ra (plasma level approximately 100 to 200 ng/ml) or saline (untreated) from day -1 until being killed on day 14. Untreated animals exhibited severe proteinuria and development renal dysfunction shown by increased serum urea and serum creatinine and reduced creatinine clearance. In contrast, IL-1ra treated animals had significantly reduced proteinuria (IL-1ra vs. untreated, P < 0.05) and maintained normal renal function (IL-1ra vs. untreated, P < 0.05). Histologically, IL-1ra treatment markedly reduced glomerular hypercellularity, glomerular necrosis and crescent formation and almost completely abrogated tubular atrophy and fibrosis. IL-1ra treatment suppressed glomerular macrophage accumulation by 57% (P < 0.01), while macrophage accumulation in the interstitium was completely abrogated and immune activation of the interstitial T cell infiltrate was prevented. This study demonstrates that IL-1 plays a key role in the pathogenesis of anti-GBM glomerulonephritis, and blocking its effects may provide a novel therapeutic approach to the treatment of human progressive glomerulonephritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / immunology
  • Complement C3 / metabolism
  • Glomerulonephritis / immunology
  • Glomerulonephritis / pathology
  • Glomerulonephritis / prevention & control*
  • Immunoglobulin G / metabolism
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / physiology
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Leukocytes / pathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Sialoglycoproteins / pharmacology*


  • Complement C3
  • IL1RN protein, human
  • Immunoglobulin G
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Receptors, Interleukin-1
  • Sialoglycoproteins