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

Authors: Lan, HY  Nikolic-Paterson, DJ  Mu, W  Vannice, JL  Atkins, RC 
Citation: Lan HY, etal., Kidney Int. 1995 May;47(5):1303-9.
Pubmed: (View Article at PubMed) PMID:7637259

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.


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RGD Object Information
RGD ID: 8551712
Created: 2014-04-10
Species: All species
Last Modified: 2014-04-10
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.