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An in vivo experimental model of BPP was used to characterize the pulmonary expression kinetics of tumor necrosis factor alpha (TNF\u03b1), interleukin-1 beta (IL-1\u03b2), and interleukin-8 (IL-8) genes and proteins during the acute phase of disease development. Cytokine expression in bronchoalveolar lavage (BAL) fluid, BAL cells, and pneumonic lung parenchyma was quantitated by northern blot analysis, enzyme-linked immunosorbent assay (ELISA), and in situ hybridization at 2, 4, 8, 16, and 24 hours after endobronchial inoculation of Pasteurella (Mannheimia) haemolytica. Expression of TNF\u03b1, IL-1\u03b2, and IL-8 was significantly increased in the airways and lung lesions of infected calves as compared with mock-infected controls. Although kinetic patterns varied, peak levels of cytokine mRNA occurred within 8 hours postinfection (PI), and peak cytokine concentrations occurred within 16 hours PI. In all samples, IL-8 was expressed to the greatest extent and TNF\u03b1 was least expressed. Expression of TNF\u03b1 was restricted to alveolar macrophages. Alveolar and interstitial macrophages produced IL-1\u03b2 and IL-8 in the first 4 hours; bronchial and bronchiolar epithelial cells were also significant sources of IL-8 during this period. By 8 hours PI, neutrophils were the dominant source of both IL-1\u03b2 and IL-8. These findings demonstrate a spatial and temporal association between pulmonary expression of inflammatory cytokines and acute lung pathology, supporting the hypothesis that cytokines contribute to inflammatory lung injury in BPP. <\/jats:p>","DOI":"10.1354\/vp.38-3-297","type":"journal-article","created":{"date-parts":[[2003,4,24]],"date-time":"2003-04-24T20:18:12Z","timestamp":1051215492000},"page":"297-310","source":"Crossref","is-referenced-by-count":67,"title":["Pulmonary Expression of Tumor Necrosis Factor Alpha, Interleukin-1 Beta, and Interleukin-8 in the Acute Phase of Bovine Pneumonic Pasteurellosis"],"prefix":"10.1177","volume":"38","author":[{"given":"C.","family":"Malazdrewich","sequence":"first","affiliation":[{"name":"Departments of Clinical and Population Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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