IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis

Abstract

Background. IL-1β 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)-β production, previously demonstrated in vitro.Methods. The in vivo roles of endogenous IL-1β and its type I receptor (IL-1RI) in renal fibrosis were studied using wild-type C57BL6 mice, IL-1β - and IL-1RI - mice with unilateral ureteric obstruction.Results. After 7 days, IL-1RI - mice (IL-1α and IL-1β deficient) were protected from injury and collagen accumulation. IL-1β - mice demonstrated some histological protection, but no reduction in α1(1) procollagen mRNA or biochemically measured collagen accumulation. Compared with obstructed kidneys from wild-type mice, TGF-β1 mRNA was reduced in IL-1RI - mice (with trends to reduced TGF-β2 and TGF-β3). Expression of a downstream TGF-β 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-1β - or IL-1RI - mice. While TNF expression was similar to wild-type mice, IFN-γ expression was reduced in both IL-1β - and IL-1RI - mice. IL-1RI - mice at 14 days showed a catch-up in fibrosis compared with wild-type mice.Conclusion. IL-1IL-1RI interactions are profibrotic in renal fibrosis. IL-1RI - mice were more protected at an early stage, associated with changes in TGF-β and downstream mediators of fibrosis, but independent of the presence of infiltrating macrophages.