Effect of IL-11 on Glomerular Expression of TGF-beta and Extracellular Matrix in Nephrotoxic Nephritis in Wistar Kyoto Rats.

BACKGROUND:The effect of interleukin-11 (IL-11) on transforming growth factor-ß (TGF-ß) is controversial and has not been examined in renal diseases. In this study, we (i) characterised the up-regulation of TGF-ß1, phospho-p38 MAPK (p-p38 MAPK) and extracellular matrix during pathogenesis of glomerulonephritis and (ii) examined the effect of rhIL-11 on these processes in vivo.METHODS:Following induction of nephrotoxic nephritis, expression of TGF-ß1, alpha-smooth muscle actin (alpha-SMA), fibronectin and p-p38 MAPK was detected in the kidney. Rats were treated either with vehicle or rhIL-11 at a high or low dose and culled on day 6.RESULTS:A high dose of rhIL-11 resulted in a significant reduction in the glomerular expression of TGF-ß1 (0.4 ± 0.1 vs. 2.04 ± 0.4 semiquantitative score, p<0.005), alpha-SMA (0.6 ± 0.2 vs. 1.5 ± 0.3, p<0.01) and fibronectin (0.6 ± 0.1 vs. 1.5 ± 0.1, p<0.02). The periglomerular expression of alpha-SMA and fibronectin was significantly reduced in rats treated with the high dose of rhIL-11 (9.6% ± 2% vs. 92% ± 2.5% of glomeruli, p<0.01; and 26% ± 4.9% vs. 94% ± 1.9% of glomeruli, p<0.005, respectively). There was a slight but insignificant reduction of p-p38 MAPK in IL-11 treated rats. Treatment with low-dose rhIL-11 did not reduce expression of these molecules.CONCLUSION:IL-11 suppresses glomerular expression of TGF-ß1 and extracellular matrix deposition in experimental glomerulonephritis.