title: Mechanical ventilation induces inflammation, lung injury, and extra-pulmonary organ dysfunction in experimental pneumonia.
abstract: Mechanical ventilation (MV) is frequently employed for the management of critically ill patients with respiratory failure. A major complication of mechanical ventilation (MV) is the development of ventilator-associated pneumonia (VAP), in which Staphylococcus aureus is a prominent pathogen. Moreover, previous studies suggest that MV may be an important cofactor in the development of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). S. aureus pulmonary infection was induced in spontaneously breathing mice (C57Bl/6) or mechanically ventilated mice to determine whether MV contributes to the development of ALI and/or systemic inflammation. The combination of MV and bacteria significantly increased the influx of neutrophils into bronchoalveolar lavage fluid (BALF), augmented pulmonary production of the proinflammatory cytokines KC, MIP-2, TNF-alpha, and IL-6, and increased alveolar-capillary permeability to proteins. MV also induced proinflammatory cytokine expression in peripheral blood, associated with extrapulmonary hepatic and renal dysfunction. Surprisingly, bacterial clearance in the lungs and extrapulmonary bacterial dissemination was not affected by MV. These data indicate that MV exacerbates both pulmonary and systemic inflammation in response to bacteria and contributes to the pathogenesis of both ALI and the multiple organ dysfunction syndrome, without necessarily affecting bacterial clearance or extra-pulmonary bacterial dissemination.
authors.affiliation: Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98103, USA. sdhanir@u.washington.edu
authors.forename: Shireesha
authors.initials: S
authors.lastname: Dhanireddy
authors.forename: William A
authors.initials: WA
authors.lastname: Altemeier
authors.forename: Gustavo
authors.initials: G
authors.lastname: Matute-Bello
authors.forename: D Shane
authors.initials: DS
authors.lastname: O'Mahony
authors.forename: Robb W
authors.initials: RW
authors.lastname: Glenny
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Martin
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004926:Escherichia coli / Q000302:isolation & purification; D007249:Inflammation / Q000209:etiology*; D017093:Liver Failure / Q000209:etiology*; D055370:Lung Injury; D051379:Mice; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000503:physiopathology*; D051437:Renal Insufficiency / Q000209:etiology*; D012121:Respiration, Artificial / Q000009:adverse effects*; D013211:Staphylococcus aureus / Q000302:isolation & purification