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 studies, however, have focused on early stages of the lung reaction. We hypothesized that chronic stages of the model may not mimic idiopathic pulmonary fibrosis, since in preliminary studies, lung volume and compliance were not decreased. Eight male Sprague-Dawley rats receiving intratracheal bleomycin (0.5 U/100 g body weight) underwent measurement of FRC, inspiratory capacity, and lung compliance 120 d later. Lung histologic changes were evaluated using light microscopy. Eight rats without intervention served as controls. Results show that our model, in early stages, has histologic changes no different from those previously described elsewhere. In chronic stages, however, the model does not behave as a restrictive syndrome: FRC is normal or increased, whereas lung compliance is normal. Focal peribronchiolar inflammation and fibrosis associated with paracicatricial emphysematous changes are the main histologic features of long-term lung remodeling after bleomycin. We conclude that while the chronic stages of the model may be informative in understanding mechanisms of fibrosis, care should be taken not to extrapolate to human idiopathic pulmonary fibrosis. We speculate that the model might resemble a particular subgroup of human interstitial lung disease, namely, those involving peribronchiolar structures.
Borzone
G
G
Department of Respiratory Diseases and Medical Research Center, Pontificia Universidad Católica de Chile, and Program of Pathology, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile. gborzone@med.puc.cl
Moreno
R
R
Urrea
R
R
Meneses
M
M
Oyarzún
M
M
Lisboa
C
C
D000818:Animals; D001761:Bleomycin; D002908:Chronic Disease; D004195:Disease Models, Animal; D005652:Functional Residual Capacity; D006801:Humans; D008168:Lung / Q000473:pathology; D008170:Lung Compliance; D008176:Lung Volume Measurements; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001761:Bleomycin