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Histopathology of the lungs revealed chronic inflammation, severe alveolar air space enlargement and septal destruction, and bronchiolitis. However, pulmonary fibrosis was very limited and only seen in the subpleural, peribronchiolar, and perivascular regions. Physiological assessment showed an increase in lung volumes and a decrease in elastic recoil characteristic of emphysema; there was no evidence of restrictive lung disease characteristic of pulmonary fibrosis. In addition, the mice raised in ambient conditions in Denver developed pulmonary hypertension. Gelatinase activity was increased in the lavage fluid from these lungs. These results suggest that in these mice TNF-\u03b1 contributed to the development of pulmonary emphysema through chronic lung inflammation and activation of the elastolytic enzymes but by itself was unable to produce significant pulmonary fibrosis.<\/jats:p>","DOI":"10.1152\/ajplung.2001.280.1.l39","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T20:49:41Z","timestamp":1514062181000},"page":"L39-L49","source":"Crossref","is-referenced-by-count":188,"title":["Overexpression of tumor necrosis factor-\u03b1 produces an increase in lung volumes and pulmonary hypertension"],"prefix":"10.1152","volume":"280","author":[{"given":"Masaki","family":"Fujita","sequence":"first","affiliation":[{"name":"Department of Medicine, National Jewish Medical and Research Center, Denver 80206; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Shannon","sequence":"additional","affiliation":[{"name":"Department of Medicine, National 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