Enhanced susceptibility to immune nephritis in DBA/1 mice is contingent upon IL-1 expression.
The DBA/1 mouse strain is particularly sensitive to experimental immune-mediated nephritis. Previous studies have indicated that various chemokines/cytokines are elevated in strains of mice susceptible to immune-mediated glomerulonephritis. One of the many elevated cytokines is IL-1. This study was designed to determine if IL-1 is essential for the development of immune-mediated nephritis in the DBA/1 mouse strain that is particularly sensitive to this disease. Both male and female DBA/1 mice and DBA/1.IL-1R1(-/-) mice were challenged with anti-GBM sera. We then compared DBA/1 mice to DBA/1.IL-1R1(-/-) mice to determine the influence of IL-1 on immune-mediated nephritis. Compared to DBA/1 mice, DBA/1.IL-1R1(-/-) mice excreted significantly less protein post anti-GBM serum challenge. None of the DBA/1.IL-1R1(-/-) mice, male or female, had a BUN higher than 22 mg/dl post-challenge whereas wild-type DBA/1 mice had significantly elevated BUN. Wild-type DBA/1 mice exhibited pronounced glomerulonephritis, with crescent formation, as well as tubulo-interstitial disease compared to DBA/1.IL1R1(-/-) mice. These findings indicate that IL-1 is necessary for the development of nephritis in DBA/1 mice and suggest that the elevated IL-1 levels in these mice may be one reason why the DBA/1 strain is particularly sensitive to multiple end organ diseases.
Xie
Chun
C
Division of Rheumatology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8884, USA.
Qin
Xiangmei
X
Jonnala
Geetha
G
Gong
Yimei
Y
Yan
Mei
M
Zong
Peijun
P
Zhou
Xin J
XJ
Mohan
Chandra
C
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D004198:Disease Susceptibility / Q000378:metabolism*; D005260:Female; D005921:Glomerulonephritis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007375:Interleukin-1 / Q000172:deficiency* / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011507:Proteinuria / Q000276:immunology; D013045:Species Specificity; D014511:Uremia / Q000235:genetics / Q000276:immunology
D015415:Biomarkers; D007375:Interleukin-1