title: Pulmonary cytokine responses during mechanical ventilation of noninjured lungs with and without end-expiratory pressure.
abstract: BACKGROUND
  Positive end-expiratory pressure (PEEP) during mechanical ventilation may impose different degrees of stress on healthy lungs. On the assumption that stress is reflected by cytokine production, we performed a translational study investigating the effect of PEEP on bronchoalveolar and systemic mediator levels in isolated perfused mouse lungs (IPL) and in patients with healthy lungs.
  
  
  METHODS
  (Part I) IPL were ventilated with end-expiratory pressures of 0, 3, 6, or 10 cm H2O and end-inspiratory pressure (EIP) levels of 10 or 25 cm H2O. Interleukin (IL)-6 and macrophage inflammatory protein-2 concentrations in the venous effluate were monitored. (Part II) Patients (nonsmokers) scheduled for elective otorhinolaryngology surgery (duration>90 min) were randomized to receive either ventilation with zero end-expiratory pressure or PEEP (10 cm H2O). Mediators in bronchoalveolar lavage, nuclear factor kappaB, (NF-kappaB)-activation in alveolar macrophages and circulating systemic mediators were monitored. Control patients underwent bronchoalveolar lavage after intubation.
  
  
  RESULTS
  In the IPL, mediator concentrations increased with increasing end-expiratory pressure at an EIP of 10 cm H2O, but decreased at 25 cm H2O EIP. In patients, bronchoalveolar IL-6, monocyte chemoattractant protein-1, and granulocyte monocyte-colony stimulating factor were increased by ventilation regardless of the PEEP level. IL-6 and IL-8 levels were moderately increased by PEEP but not zero end-expiratory pressure. Nuclear factor kappaB DNA binding activity in alveolar macrophages and systemic mediator levels did not change.
  
  
  CONCLUSIONS
  On the basis of the premise that cytokine levels may indicate mechanical stress, our findings indicate that even low tidal volume ventilation causes some stress. PEEP is beneficial at high inspiratory pressure, but imposes moderate stress at low inspiratory pressure.
authors.affiliation: Department of Anesthesiology, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany. Torsten.Meier@uk-sh.de
authors.forename: Torsten
authors.initials: T
authors.lastname: Meier
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lange
authors.forename: Hilke
authors.initials: H
authors.lastname: Papenberg
authors.forename: Malte
authors.initials: M
authors.lastname: Ziemann
authors.forename: Christina
authors.initials: C
authors.lastname: Fentrop
authors.forename: Ulrike
authors.initials: U
authors.lastname: Uhlig
authors.forename: Peter
authors.initials: P
authors.lastname: Schmucker
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlig
authors.forename: Cordula
authors.initials: C
authors.lastname: Stamme
mesh_terms: D000328:Adult; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D054426:Chemokine CXCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D013517:Otorhinolaryngologic Surgical Procedures; D011175:Positive-Pressure Respiration; D012123:Pulmonary Ventilation; D012121:Respiration, Artificial; D013990:Tidal Volume
chemical_list: D054426:Chemokine CXCL2; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D016178:Granulocyte-Macrophage Colony-Stimulating Factor