title: Impaired pulmonary inflammatory responses are a prominent feature of streptococcal pneumonia in mice with experimental emphysema.
abstract: Little is known about why patients with chronic obstructive pulmonary disease are susceptible to bacterial infections. Using an animal model of pulmonary emphysema, we investigated the inflammatory responses to bacterial infection. After intratracheal infection with Streptococcus pneumoniae (10(3)-10(7) cfu/mouse), the control mice did not die. However, the mice with emphysema died in a dose-dependent manner. Bronchoalveolar lavage fluid, examined 24 hours after infection showed that the numbers of total cells and neutrophils, in addition to murine tumor necrosis factor-alpha and macrophage inflammatory protein-2 concentrations, were significantly less in the mice with emphysema compared with the control mice. Histopathologic findings revealed that the alveoli were filled with inflammatory cells and exudate in the control mice but not in the mice with emphysema. Seventy-two hours after infection, serum cytokine levels were significantly higher in the mice with emphysema, and significant numbers of S. pneumoniae were detected in both the whole lung tissues and the blood of mice with emphysema. These findings suggest that the inflammatory response in mice with emphysema was impaired at the site of bacterial infection despite the bacteremia, which accelerated severe systemic inflammatory responses. Accordingly, intra-alveolar but not systemic immune responses to bacterial infection were impaired in the presence of experimental emphysema.
authors.affiliation: First Department of Internal Medicine, Yamagata University School of Medicine, Iida-Nishi, Yamagata, Japan. BYC04033@nifty.ne.jp
authors.forename: Sumito
authors.initials: S
authors.lastname: Inoue
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nakamura
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Otake
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Kyoko
authors.initials: K
authors.lastname: Terashita
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeda
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D016207:Cytokines / Q000032:analysis / Q000097:blood; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D008168:Lung / Q000382:microbiology / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D011656:Pulmonary Emphysema / Q000150:complications* / Q000276:immunology / Q000401:mortality; D013296:Streptococcus pneumoniae / Q000302:isolation & purification; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha