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Updated: Jun 22, 2026
Mouse Model of Acute to Chronic Kidney Disease Transition Induced by Renal Ischemia/Reperfusion Injury
Published on: February 10, 2026
IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis
Lynelle K Jones1, Kim M O'Sullivan, Timothy Semple
1Department of Medicine, Centre for Inflammatory Diseases, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
Background:
IL-1beta has the potential to promote progressive renal disease by effects on macrophage recruitment and activation or by effects mediated through tubular cell transforming growth factor (TGF)-beta production, previously demonstrated in vitro.
Methods:
The in vivo roles of endogenous IL-1beta and its type I receptor (IL-1RI) in renal fibrosis were studied using wild-type C57BL/6 mice, IL-1beta(-/-) and IL-1RI(-/-) mice with unilateral ureteric obstruction.
Results:
After 7 days, IL-1RI(-/-) mice (IL-1alpha and IL-1beta deficient) were protected from injury and collagen accumulation. IL-1beta(-/-) mice demonstrated some histological protection, but no reduction in alpha1(1) procollagen mRNA or biochemically measured collagen accumulation. Compared with obstructed kidneys from wild-type mice, TGF-beta1 mRNA was reduced in IL-1RI(-/-) mice (with trends to reduced TGF-beta2 and TGF-beta3). Expression of a downstream TGF-beta effector, connective tissue growth factor, was decreased in IL-1RI(-/-) mice. IL-1RI(-/-) mice exhibited less tubulointerstitial apoptosis compared with wild-type mice. Macrophage infiltration and adhesion molecule mRNA expression was unchanged in IL-1beta(-/-) or IL-1RI(-/-) mice. While TNF expression was similar to wild-type mice, IFN-gamma expression was reduced in both IL-1beta(-/-) and IL-1RI(-/-) mice. IL-1RI(-/-) mice at 14 days showed a catch-up in fibrosis compared with wild-type mice.
Conclusion:
IL-1/IL-1RI interactions are profibrotic in renal fibrosis. IL-1RI(-/-) mice were more protected at an early stage, associated with changes in TGF-beta and downstream mediators of fibrosis, but independent of the presence of infiltrating macrophages.
