Abstract
Pulmonary fibrosis (PF) is characterized by remodeled lung structure and impaired respiratory function. Prostacyclin has been shown to exert antifibrotic properties, and the role of prostanoids in PF is under investigation. We aimed to examine the therapeutic effect of the synthetic prostacyclin analogue treprostinil in an animal model of PF. Adult C57BL6 mice (n=7-9/group) were challenged intratracheally with bleomycin sulfate (BLM; 2mg/mL) or saline (day 0). Treprostinil administration or vehicle started 24 hr prior BLM via orotracheal aspiration, (40µg/Kg/12 hr).Evaluation of lung mechanics, plus collection of bronchoalveolar lavage fluid (BALF) and lung tissue samples were performed at day 7, 14 and 21 post BLM to estimate lung pathology. BLM challenge resulted in increased lung elastance and decreased lung compliance, altered structural architecture, and increased cellular and protein content of the alveolar compartment observed already at day 7, denoting inflammation. Prophylactic treatment with treprostinil: i) improved lung mechanics in most time points, ii) decreased BALF cellularity at all time points and iii) starting at day 14, decreased protein BALF levels and attenuated lung inflammatory and fibrotic scores. Soluble collagen levels at day 21 post BLM were increased from 526.4±28.4 (controls; mean ±SEM) to 861.7±44.9 µg/mL denoting fibrosis, while they were decreased in treprostinil-treated animals (677.8±31.03 µg/mL; p Pretreatment with treprostinil in our BLM model maintained respiratory function, reduced airspace inflammation and lung pathology, and attenuated collagen deposition. Our results suggest that treprostinil may be an effective treatment of pulmonary fibrosis.
Published Version
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