IL-9 Blockade Suppresses Silica-induced Lung Inflammation and Fibrosis in Mice

Recapitulative animal models of idiopathic pulmonary fibrosis (IPF) and related diseases are lacking, which inhibits our ability to fully clarify the pathogenesis of these diseases. Although lung fibrosis in mouse models is often induced by bleomycin, silica-induced lung fibrosis is more sustainable and more progressive. Therefore, in this study, we sought to elucidate the mediator(s) responsible for the pathogenesis of lung fibrosis, through the use of a mouse model of silica-induced lung fibrosis. With a single nasal administration of 16 mg of silica, lung inflammation (assessed by elevated cellular components in the BAL fluids [BALFs]) and lung fibrosis (assessed by lung histology and lung hydroxyproline levels) were induced and sustained for as long as 24 weeks. Of the mediators measured in the BALFs, IL-9 was characteristically elevated gradually, and peaked at 24 weeks after silica administration. Treatment of silica-challenged mice with anti–IL-9–neutralizing antibody inhibited lung fibrosis, as as...