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.
ASJC Scopus subject areas
- Immunology and Allergy