Chronic administration of IL-6 enhanced fibrotic response after IR. WT mice were subjected to sham surgery or IR. Three days after IR, mice received either vehicle (0.1% BSA) or IL-6 (10 ng·animal−1·day−1) for 2 wk. Fibrosis was determined by Masson's trichrome staining, and fibrotic gene expression was quantified by RT-PCR. A: sham-operated WT kidney does not show any fibrosis. B: IR induced a large increase in interstitial fibrosis (blue staining). C: IL-6 administration enhanced fibrosis. D: quantification of collagen I, collagen IV, and transforming growth factor (TGF)-β1 gene expression by RT-PCR. IR induced a significant increase in collagen I, collagen IV, and TGF-β1 expression. IL-6 administration enhanced collagen I mRNA expression. *P < 0.05 vs. sham control. #P < 0.05 vs. vehicle-treated IR. E: kidney function was determined by measuring serum creatinine. IL-6 administration does not alter serum creatinine levels compared with vehicle-treated IR. *P < 0.001 vs. sham control. F: Western blot analysis of collagen IV, α-SMA, and phospho-STAT3 by Western blot analysis. IL-6 administration enhanced IR-induced collagen and SMA expression. G: densitometric quantification of Western blot analysis of collagen IV, α-SMA, and phospho-STAT3. *P < 0.001 vs. sham control. #P < 0.05 vs. IR+vehicle treated; n = 4–6.