Interleukin-1 receptor antagonist halts the progression of established crescentic glomerulonephritis in the rat

Kidney Int. 1995 May;47(5):1303-9. doi: 10.1038/ki.1995.185.


The pathogenic role of interleukin-1 (IL-1) in the progression of established rat crescentic glomerulonephritis was investigated by administration of the interleukin-1 receptor antagonist (IL-1ra). Passive accelerated antiglomerular basement membrane (GBM) disease was induced in three groups of six rats. One group was killed on day 7 with no treatment. The other groups received a constant infusion of IL-1ra or saline from day 7 until being killed on day 21. All animals developed moderate glomerular injury, a significant loss of renal function and marked histological damage including crescent formation by day 7. Saline treated animals showed a significant deterioration in these parameters over days 7 to 21. In contrast, animals treated with the IL-1ra over this period showed stabilization of glomerular injury (protein-uria; P < 0.001) and a recovery of normal renal function (creatinine clearance; P < 0.05). Histologically, IL-1ra treatment suppressed glomerular cell proliferation (PCNA expression; P < 0.001) and significantly inhibited crescent formation (P < 0.005), glomerular sclerosis (P < 0.005), tubular atrophy (P < 0.05) and interstitial fibrosis (P < 0.05). A key finding was that IL-1ra treatment not only stopped renal leukocyte accumulation over days 7 to 21 (P < 0.01), but that treatment also suppressed immune activation of the infiltrate (P < 0.01). In conclusion, this study provides direct evidence that IL-1 plays a key role in the progressive/chronic phase of renal injury in experimental crescentic glomerulonephritis and indicates that IL-1ra treatment may be of therapeutic benefit in human rapidly progressive crescentic glomerulonephritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cell Division
  • Creatinine / blood
  • Disease Progression
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / metabolism
  • Glomerulonephritis / pathology
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / physiology*
  • Leukocytes / physiology
  • Male
  • Proteinuria
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Sialoglycoproteins / pharmacology*
  • Urea / blood


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Receptors, Interleukin-1
  • Sialoglycoproteins
  • Urea
  • Creatinine