title: Anti-inflammatory and anti-fibrotic effects of sirolimus on bleomycin-induced pulmonary fibrosis in rats.
abstract: OBJECTIVE
  Pulmonary fibrosis is a devastating disease with a poor prognosis. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. The aim of this study was to evaluate the anti-inflammatory and anti-fibrotic effects of sirolimus (SRL), which is a potential anti-fibrotic agent, by using bleomycin (BLM)-induced pulmonary fibrosis model in rats.
  
  
  METHODS
  A single intra-tracheal injection of BLM (2.5 U/kg) was administered and sirolimus (2.5 mg/kg/day) was given orally, beginning either one day before (early SRL) or nine days after (late SRL) the BLM administration. The effect of SRL on fibrosis was studied by analysis of cytokine levels in BAL fluid, measurement of lung tissue hydroxyproline (HPL) content and histopathological examination.
  
  
  RESULTS
  Both early and late SRL administrations caused a decrease in the levels of IL-13, PDGF-A and TGF-β1 (p=0.001) and an increase in IFN-γ levels (p=0.001) in BAL fluid. Early and late SRL also caused a decrease in HPL content (p=0.001). Early sirolimus caused a significant decrease in fibrosis score (p=0.001), while late SRL did not.
  
  
  CONCLUSIONS
  Sirolimus was effective in BLM-induced pulmonary fibrosis model, especially in the early phases of the disease.
authors: Department of Pulmonary Medicine, Selcuk University, Konya-Turkey. baykaltulek@yahoo.com
authors: Baykal
authors: B
authors: Tulek
authors: Esen
authors: E
authors: Kiyan
authors: Hatice
authors: H
authors: Toy
authors: Aysel
authors: A
authors: Kiyici
authors: Cuneyt
authors: C
authors: Narin
authors: Mecit
authors: M
authors: Suerdem
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018793:Interleukin-13; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; C075278:platelet-derived growth factor A; D001761:Bleomycin; D007371:Interferon-gamma; D020123:Sirolimus