Suppression of experimental glomerulonephritis by the interleukin-1 receptor antagonist: Inhibition of intercellular adhesion molecule-1 expression

David J. Nikolic-Paterson, Hui Y. Lan, Prudence A. Hill, James L. Vannice, Robert C. Atkins

Research output: Contribution to journalArticleResearchpeer-review

54 Citations (Scopus)


Interleukin-1 is a proinflammatory cytokine produced in glomerulonephritis. Blocking the action of interleukin-1 by the administration of the interleukin1 receptor antagonist (IL-1ra) has been shown to prevent renal function impairment, reduce glomerular injury, inhibit leukocyte infiltration, and suppress tubulointerstitial damage in experimental antiglomerular basement membrane disease. A key mechanism in the entry of leukocytes into the kidney is the interaction between the interleukin-1 inducible intercellular adhesion molecule-1 (ICAM-1; CD54) and lymphocyte function-associated antigen-1 (CD11a/ CD 18). Therefore, this study investigated whether the inhibition of this mechanism was the means by which IL-1ra suppressed leukocyte infiltration in rat accelerated antiglomerular basement membrane glomerulonephritis. Disease was induced in two groups of six rats; animals were treated by constant sc infusion of recombinant human IL-1ra or saline from the initiation of disease until being euthanized 14 days later. In saline-treated animals, there was marked up-regulation of ICAM-1 in the glomerulus and interstitium, which was associated with leukocyte infiltration. In particular, focal accumulation of CD11a+ and CD18+ cells was apparent in areas of tubulointerstitial damage exhibiting intense ICAM-1 expression. IL-1ra treatment partially reduced glomerular ICAM-1 expression and leukocyte infiltration. However, IL-1ra treatment resulted in a dramatic inhibition of interstitial ICAM-1 expression, interstitial leukocyte infiltration, and tubulointerstitial damage. In conclusion, this study has shown that interleukin-1 is a major inducer of ICAM-1 expression within the renal tubulointerstitium - a process associated with focal leukocyte infiltration and tubulointerstitial damage. This is the first demonstration of a specific mechanism by which interleukin-1 participates in the pathogenesis of renal injury.

Original languageEnglish
Pages (from-to)1695-1700
Number of pages6
JournalJournal of the American Society of Nephrology
Issue number9
Publication statusPublished - 1 Mar 1994
Externally publishedYes


  • Adhesion molecules
  • Immunohistochemistry
  • Interteukin-1
  • Leukocytes
  • Lymphocyte function-associated antigen-1

Cite this