Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis

Administration of bleomycin into the lungs of experimental animals has been utilized as a model to understand human pulmonary fibrosis. Most of the st udies, however, have focused on early stages of the lung reaction. We hypot hesized that chronic stages of the model may not mimic idiopathic pulmonary fibrosis, since in preliminary studies, lung volume and compliance were no t decreased. Eight male Sprague-Dawley rats receiving intratracheal bleomyc in (0.5 U/100 g body weight) underwent measurement of FRC, inspiratory capa city, and lung compliance 120 d later. Lung histologic changes were evaluat ed using light microscopy. Eight rats without intervention served as contro ls. Results show that our model, in early stages, has histologic changes no different from those previously described elsewhere. In chronic stages, ho wever, the model does not behave as a restrictive syndrome: FRC is normal o r increased, whereas lung compliance is normal. Focal peribronchiolar infla mmation and fibrosis associated with paracicatricial emphysematous changes are the main histologic features of long-term lung remodeling after bleomyc in. We conclude that while the chronic stages of the model may be informati ve in understanding mechanisms of fibrosis, care should be taken not to ext rapolate to human idiopathic pulmonary fibrosis. We speculate that the mode l might resemble a particular subgroup of human interstitial lung disease, namely, those involving peribronchiolar structures.