title: Host response to mechanical ventilation for viral respiratory tract infection.
abstract: Respiratory syncytial virus (RSV) bronchiolitis causes severe respiratory tract infection in infants, frequently necessitating mechanical ventilatory support. However, life-saving, mechanical ventilation aggravates lung inflammation. We set up a model to dissect the host molecular response to mechanical ventilation in RSV infection. Furthermore, the response to induced hypercapnic acidosis, reported to dampen the inflammatory response to mechanical ventilation in non-infectious models, was assessed. BALB/c mice were inoculated with RSV or mock-suspension and ventilated for 5 h on day 5 post inoculation. Mechanical ventilation of infected mice resulted in enhanced cellular influx and increased concentrations of pro-inflammatory cytokines in the bronchoalveolar space. Microarray analysis showed that enhanced inflammation was associated with a molecular signature of a stress response to mechanical ventilation with little effect on the virus-induced innate immune response. Hypercapnic acidosis during mechanical ventilation of infected mice did not change host transcript profiles. We conclude that mechanical ventilation during RSV infection adds a robust but distinct molecular stress response to virus-induced innate immunity activation, emphasising the importance of lung-protective mechanical ventilation strategies. Induced hypercapnic acidosis has no major effect on host transcription profiles during mechanical ventilation for RSV infection, suggesting that this is a safe approach to minimise ventilator-induced lung injury.
authors.affiliation: Dept of Pediatric Intensive Care, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marije P
authors.initials: MP
authors.lastname: Hennus
authors.forename: Riny
authors.initials: R
authors.lastname: Janssen
authors.forename: Jeroen L A
authors.initials: JL
authors.lastname: Pennings
authors.forename: Hennie M
authors.initials: HM
authors.lastname: Hodemaekers
authors.forename: Debby
authors.initials: D
authors.lastname: Kruijsen
authors.forename: Nicolaas J
authors.initials: NJ
authors.lastname: Jansen
authors.forename: Linde
authors.initials: L
authors.lastname: Meyaard
authors.forename: Adrianus J
authors.initials: AJ
authors.lastname: van Vught
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Bont
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016000:Cluster Analysis; D006439:Hemodynamics; D006935:Hypercapnia / Q000378:metabolism; D007249:Inflammation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012121:Respiration, Artificial / Q000379:methods*; D018357:Respiratory Syncytial Virus Infections / Q000628:therapy*; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000502:physiology; D013997:Time Factors; D055397:Ventilator-Induced Lung Injury / Q000175:diagnosis