TY - JOUR
T1 - Interleukin-1 receptor antagonist halts the progression of established crescentic glomerulonephritis in the rat
AU - Lan, Hui Y.
AU - Nikolic-Paterson, David J.
AU - Mu, Wei
AU - Vannice, James L.
AU - Atkins, Robert C.
PY - 1995/1/1
Y1 - 1995/1/1
N2 - The pathogenic role of interleukin-1 (IL-1) in the progression of established rat crescentic glomerulonephritis was investigated by administration of the interleukin-l 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 IL1ra over this period showed stabilization of glomerular injury (proteinuria; 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), hut 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.
AB - The pathogenic role of interleukin-1 (IL-1) in the progression of established rat crescentic glomerulonephritis was investigated by administration of the interleukin-l 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 IL1ra over this period showed stabilization of glomerular injury (proteinuria; 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), hut 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.
UR - http://www.scopus.com/inward/record.url?scp=0029045960&partnerID=8YFLogxK
U2 - 10.1038/ki.1995.185
DO - 10.1038/ki.1995.185
M3 - Article
C2 - 7637259
VL - 47
SP - 1303
EP - 1309
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 5
ER -
