title: Bleomycin delivery by osmotic minipump: similarity to human scleroderma interstitial lung disease.
abstract: The interstitial lung diseases (ILD) include a large number of chronic, progressive, irreversible respiratory disorders involving pulmonary fibrosis, the most common of which are idiopathic pulmonary fibrosis and scleroderma lung disease (SSc ILD). Because bleomycin causes lung fibrosis when used in cancer chemotherapy, it is used to model human ILD in rodents. In most studies, bleomycin has been delivered directly into the lung by intratracheal or intraoral administration. Here we have compared the effects in mice of bleomycin delivered directly into the lungs (direct model) or systemically using osmotic minipumps (pump model) to determine which more closely resembles human ILD. The pump model is more similar to human SSc ILD in that: 1) lung injury/fibrosis is limited to the subpleural portion of the lung in the pump model and in SSc ILD, whereas the entire lung is affected in the direct model; 2) conversely, there is massive inflammation throughout the lung in the direct model, whereas inflammation is limited in the pump model and in SSc ILD; 3) hypertrophic type II alveolar epithelial cells are present at high levels in SSc ILD and in the pump model but not in the direct model; and 4) lung fibrosis is accompanied by dermal fibrosis. The pump model is also move convenient and humane than the direct model because there is less weight loss and mortality.
authors.affiliation: Division of Rheumatology and Immunology, Dept. of Medicine, Medical Univ. of South Carolina, STB 233, 114 Doughty St., Charleston, SC 29425. hoffmas@musc.edu.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lee
authors.forename: Charles
authors.initials: C
authors.lastname: Reese
authors.forename: Michael
authors.initials: M
authors.lastname: Bonner
authors.forename: Elena
authors.initials: E
authors.lastname: Tourkina
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Hajdu
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Riemer
authors.forename: Richard M
authors.initials: RM
authors.lastname: Silver
authors.forename: Richard P
authors.initials: RP
authors.lastname: Visconti
authors.forename: Stanley
authors.initials: S
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001761:Bleomycin / Q000008:administration & dosage*; D051242:Caveolin 1 / Q000378:metabolism; D016503:Drug Delivery Systems; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D007260:Infusion Pumps; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009995:Osmosis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D051242:Caveolin 1; D016326:Extracellular Matrix Proteins; D001761:Bleomycin
keywords: fibrosis; inflammation; type II pneumocytes