title: Mechanical ventilation enhances lung inflammation and caspase activity in a model of mouse pneumovirus infection.
abstract: Severe infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury (ALI). Accumulating evidence suggests that mechanical ventilation (MV) is an important cofactor in the development of ALI by modulating the host immune responses to bacteria. This study investigates whether MV enhances the host response to pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for RSV infection in humans. BALB/c mice were inoculated intranasally with diluted clarified lung homogenates from mice infected with PVM strain J3666 or uninfected controls. Four days after inoculation, the mice were subjected to 4 h of MV (tidal volume, 10 ml/kg) or allowed to breathe spontaneously. When compared with that of mice inoculated with PVM only, the administration of MV to PVM-infected mice resulted in increased bronchoalveolar lavage fluid concentrations of the cytokines macrophage inflammatory protein (MIP)-2, MIP-1alpha (CCL3), and IL-6; increased alveolar-capillary permeability to high molecular weight proteins; and increased caspase-3 activity in lung homogenates. We conclude that MV enhances the activation of inflammatory and caspase cell death pathways in response to pneumovirus infection. We speculate that MV potentially contributes to the development of lung injury in patients with RSV infection.
authors.affiliation: Pediatric Intensive Care Unit, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Reinout A
authors.initials: RA
authors.lastname: Bem
authors.forename: Job B M
authors.initials: JB
authors.lastname: van Woensel
authors.forename: Albert P
authors.initials: AP
authors.lastname: Bos
authors.forename: Amy
authors.initials: A
authors.lastname: Koski
authors.forename: Alex W
authors.initials: AW
authors.lastname: Farnand
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Domachowske
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Martin
authors.forename: Gustavo
authors.initials: G
authors.lastname: Matute-Bello
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000276:immunology / Q000821:virology; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D020169:Caspases / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D029122:Murine pneumonia virus; D010539:Permeability; D011014:Pneumonia / Q000209:etiology / Q000276:immunology / Q000821:virology*; D011024:Pneumonia, Viral / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018186:Pneumovirus Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods; D019562:Viral Load
chemical_list: D016207:Cytokines; D020169:Caspases