Abstract for presentation at Australia and New Zealand Society of Nephrology Annual Scientific Conference

Endogenous IL-1/IL-1R1 interactions are Profibrotic in Experimental Renal Fibrosis in vivo

  • Ms Lynelle Jones, Monash University Department of Medicine, Australia
  • Mr Timothy Semple, Monash University Department of Medicine, Australia
  • Ms Kim O'Sullivan, Monash University Department of Medicine, Australia
  • Dr Kei Fukami, The Baker Heart Research Insititute, Australia
  • Prof Stephen Holdsworth, Monash University Department of Medicine, Australia
  • A/Prof A Richard Kitching, Monash University Department of Medicine, Australia

    • IL-1b possesses profibrotic effects in models of renal fibrosis in vitro, and is pathogenetic in progression of injury resulting from adaptive immune responses targeting the kidney. The in vivo role of endogenous IL-1b and the IL-1 type I receptor in renal fibrosis was studied using WT C57BL/6 mice, IL-1b-/- and IL-1R1-/- mice developing unilateral ureteric obstruction (UUO). Seven days after UUO, IL-1R1-/- mice (functionally deficient in IL-1a and IL-1b signaling), were protected from histological injury, and collagen accumulation. IL-1b-/- mice were protected, but to a lesser degree. There was at least a trend (in some cases significant) to reduced expression of TGF-b1, TGF-b2 and TGF-b3 mRNA in both IL-1b-/- and IL-1R1-/- mice. CTGF mRNA expression was decreased in IL-1R1-/- mice. IL-1R1-/- mice expressed less aSMA mRNA, although the proportion of the tubulointerstitium covered by aSMA-expressing cells (as a marker for myofibroblasts) was similar in all groups. Macrophage infiltration (scoring of F4/80+ cells) was unchanged in IL-1b-/- or IL-1R1-/- mice. Other proinflammatory cytokines were assessed. IFN-g mRNA expression was reduced in IL-1b-/- and IL-1R1-/- mice, but TNF and MIF mRNA expression were similar to C57BL/6 mice. IL-1R1-/- mice at two weeks showed a catch-up in indices of fibrosis compared with WT mice such that values were not significantly reduced. These studies demonstrate that IL-1/IL-1R1 interactions are profibrotic in experimental interstitial fibrosis in vivo, independent of adaptive immune responses. IL-1R1-/- mice were more protected; related to changes in TGF-b and downstream mediators, but independent of the presence of infiltrating macrophages.

    Conference Organiser - ICMS Pty Ltd