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

Endogenous IL-4 does not Promote Renal Fibrosis induced by Unilateral Ureteric Ligation

  • 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
  • Prof Stephen Holdsworth, Monash University Department of Medicine, Australia
  • A/Prof A Richard Kitching, Monash University Department of Medicine, Australia

    • IL-4 has important effects on T cell immune responses to antigens. In addition to its effects on T cells, IL-4 has anti-inflammatory effects on macrophages. However, IL-4 has the capacity in vitro to increase collagen production by renal cells. The effects of IL-4 in renal fibrosis independent of adaptive immune responses are not known. The role of endogenous IL-4 in renal interstitial fibrosis was studied by using IL-4 deficient mice (BALB/c) developing unilateral ureteric obstruction (UUO). Studied at one and three weeks after UUO, the degree of fibrosis (point counting for interstitial collagen by picro-sirius red, biochemical measurement of collagen accumulation and mRNA for the a1 chain of Type 1 procollagen [one week]) were similar in the both the presence and the absence of IL-4. Macrophage infiltrates and a-smooth muscle actin (both by immunostaining) were similar. At one week, analysis of mRNA for intrarenal molecular mediators of inflammation showed no difference in TNF or MIF but a trend to reduced IFN-g expression. IL-4 did not affect mRNA for the TGF-b isoform TGF-b1, but TGF-b2 mRNA expression was reduced (WT 274±54, IL-4-/- 121±32 arbitrary units [AU]; P=0.04) and there was a trend to reduced TGF-b3 mRNA expression (WT 52±7, IL-4-/- 35±5AU; P=0.07) in the absence of IL-4. Therefore, while IL-4 may play some role in regulating expression of TGF-b isoforms, it does not play a significant profibrotic role in this model of interstitial fibrosis.

    Conference Organiser - ICMS Pty Ltd