03 BR TULEK.indd

Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-infl ammatory properties of statins. The purpose of this study was to evaluate the anti-infl ammatory eff ect of simvastatin on bleomycin (BLM)-induced pulmonary fi brosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate-buff ered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The eff ect of simvastatin on pulmonary fi brosis was studied by measurements of IL-13, PDGF, IFN-γ, TGF-β1 levels in bronchoalveolar lavage (BAL) fl uid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused signifi cant change in BAL fl uid cytokine levels and increased both HPL content and histopathological score (p<0.001 for all). While LD simvastatin had no eff ect on cytokine levels, HD signifi cantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05) and TGF-β1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05). Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no eff ect on a BLMinduced pulmonary fi brosis model, while the high dose caused partial improvement in profi brotic cytokine levels.