Treatment of pulmonary fibrosis through normalization of alveolar macrophages

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronically advanced interstitial lung disease with unclear etiology and poor prognosis. Despite numerous studies, the pathogenesis of IPF has not been completely understood. In this study, we searched for drug that can decrease chronic inflammation without deteriorating fibrosis. We found fenofibrate, PPARα agonist clinically used to control dyslipidemia, had therapeutic effects on through normalization alveolar macrophages. first showed 6 days oral administration fenofibrate blocked progression bleomycin-induced resolved inflammation. addition, suppressed LPS-induced pro-inflammatory mediators in bone marrow-derived macrophages PPARα-independent manner; however, it promoted expression tissue repair anti-inflammatory genes. Finally, examined pro-inflammatory, tissue-repair, genes at 2 or after mice advancing Administration resulted decreased proinflammatory cytokines increased day 2. However, gene pattern fenofibrate-treated became similar naïve Taken together, study suggests rapidly reprogram inflammatory macrophage polarization toward normal state transient resolving stage, which linked amelioration