Anti-inflammatory and anti-fibrotic effects of sirolimus on bleomycin-induced pulmonary fibrosis in rats

Purpose: 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-beta 1 (p=0.001) and an increase in IFN-beta 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. Conclusion: Sirolimus was effective in BLM-induced pulmonary fibrosis model, especially in the early phases of the disease.