Suppression of experimental glomerulonephritis by the interleukin-1 receptor antagonist: inhibition of intercellular adhesion molecule-1 expression.
Interleukin-1 is a proinflammatory cytokine produced in glomerulonephritis. Blocking the action of interleukin-1 by the administration of the interleukin-1 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/CD18). 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, In 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 tubulo-interstitium--a process associated with focal leukocyte infiltration and tubulointerstitial damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Nikolic-Paterson
D J
DJ
Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
Lan
H Y
HY
Hill
P A
PA
Vannice
J L
JL
Atkins
R C
RC
D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D007106:Immune Sera / Q000276:immunology; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012016:Reference Values; D013194:Staining and Labeling
D015815:Cell Adhesion Molecules; D007106:Immune Sera; D017472:Receptors, Interleukin-1; D018799:Intercellular Adhesion Molecule-1