Abstract
Chronic idiopathic pulmonary fibrosis (IPF) is a progressive, fatal, and untreatable disease with unclear etiology. There are few models of this chronic pathology, and although delivery of bleomycin to induce acute lung injury is the most common animal model of pulmonary fibrosis, there is considerable uncertainty about whether this acute injury resolves in those animals that survive. In this report, we have systematically followed groups of mice for up to 6 months following a single insult of bleomycin. We assessed changes in lung function and pathology over this time course, with measurements of the diffusion capacity for carbon monoxide, lung mechanics, quantitative stereology, and collagen. Our results show that, while there is some repair over this extended time course, the injury in the lung never fully resolves. This persistent degree of fibrosis may have similarities to many features of human IPF. Thus, these chronic fibrotic changes in mouse lungs could be a useful model to evaluate potential therapeutic interventions to accelerate repair and possible treat this debilitating disease.
Highlights
The most common animal model of pulmonary fibrosis involves a single intratracheal or intranasal delivery of bleomycin to lung
Perhaps the most relevant one is that idiopathic pulmonary fibrosis (IPF) is a chronic disease that develops over a long time span, whereas the conventional single insult bleomycin model is generally studied less than a month following an acute lung insult
Despite much evidence to the contrary in murine models (Phan et al 1981; Izbicki et al 2002; Gharaee-Kermani et al 2005; Lawson et al 2005), the mice we studied do not recover from the initial bleomycin injury, and that the chronic fibrosis that develops involves decreased lung volumes, increased lung stiffness, impaired gas exchange, and increased inflammatory cell a 2014 The Authors
Summary
The most common animal model of pulmonary fibrosis involves a single intratracheal or intranasal delivery of bleomycin to lung. This insult generally results in a dose-dependent damage to the lung, characterized by inflammatory cell infiltrates, collagen deposition, and parenchymal consolidation. The lungs are generally studied 7–14 days following a single insult, and there is often an implicit assumption that if the mice do not die, the lungs will recover and the mice will return to normal While this bleomycin model has some gross similarities to human idiopathic pulmonary fibrosis (IPF), there are several obvious and substantial differences (Thrall and Scalise 1995; Chua et al 2005).
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