title: Enhanced susceptibility to immune nephritis in DBA/1 mice is contingent upon IL-1 expression.
abstract: 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.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8884, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Xie
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Qin
authors.forename: Geetha
authors.initials: G
authors.lastname: Jonnala
authors.forename: Yimei
authors.initials: Y
authors.lastname: Gong
authors.forename: Mei
authors.initials: M
authors.lastname: Yan
authors.forename: Peijun
authors.initials: P
authors.lastname: Zong
authors.forename: Xin J
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
mesh_terms: 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
chemical_list: D015415:Biomarkers; D007375:Interleukin-1