title: Inhaled IL-10 reduces biotrauma and mortality in a model of ventilator-induced lung injury.
abstract: BACKGROUND
  High-pressure ventilation induces barotrauma and pulmonary inflammation, thus leading to ventilator-induced lung injury (VILI). By limiting the pulmonal inflammation cascade the anti-inflammatory cytokine interleukin (IL)-10 may have protective effects. Via inhalation, IL-10 reaches the pulmonary system directly and in high concentrations.
  
  
  METHODS
  Thirty six male, anesthetized and mechanically ventilated Sprague-Dawley rats were randomly assigned to the following groups (n=9, each): SHAM: pressure controlled ventilation with p(max)=20cmH(2)O, PEEP=4; VILI: ventilator settings were changed for 20min to p(max)=45cmH(2)O, PEEP=0; IL-10(high): inhalation of 10microg/kg IL-10 prior to induction of VILI; and IL-10(low): inhalation of 1microg/kg IL-10 prior to induction of VILI. All groups were ventilated and observed for 4h.
  
  
  RESULTS
  High-pressure ventilation increased the concentrations of macrophage inflammatory protein (MIP)-2 and IL-1beta in bronchoalveolar lavage fluid (BALF) and plasma. This effect was reduced by the inhalation of IL-10 (10microg/kg). Additionally, IL-10 increased the animal survival time (78% vs. 22% 4-h mortality rate) and reduced NO-release from ex vivo cultured alveolar macrophages. Moreover, VILI-induced pulmonary heat shock protein-70 expression was reduced by IL-10 aerosol in a dose-dependent manner. Similarly, the activation of matrix metalloproteinase (MMP)-9 in BALF was reduced dose-dependently by IL-10. IL-10-treated animals showed a lower macroscopic lung injury score and less impairment of lung integrity and gas exchange.
  
  
  CONCLUSIONS
  Prophylactic inhalation of IL-10 improved survival and reduced lung injury in experimental VILI. Results indicate that this effect may be mediated by the inhibition of stress-induced inflammation and pulmonary biotrauma.
authors.affiliation: University Hospital of Ludwig-Maximilians-University, Munich, Germany. sandra.hoegl@med.uni-muenchen.de
authors.forename: Sandra
authors.initials: S
authors.lastname: Hoegl
authors.forename: Kim A
authors.initials: KA
authors.lastname: Boost
authors.forename: Holger
authors.initials: H
authors.lastname: Czerwonka
authors.forename: Andrea
authors.initials: A
authors.lastname: Dolfen
authors.forename: Patrick
authors.initials: P
authors.lastname: Scheiermann
authors.forename: Heiko
authors.initials: H
authors.lastname: Muhl
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zwissler
authors.forename: Christian
authors.initials: C
authors.lastname: Hofstetter
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054426:Chemokine CXCL2 / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000032:analysis / Q000097:blood; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D011175:Positive-Pressure Respiration / Q000009:adverse effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055397:Ventilator-Induced Lung Injury / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*
chemical_list: D015415:Biomarkers; D054426:Chemokine CXCL2; D018840:HSP70 Heat-Shock Proteins; D053583:Interleukin-1beta; D016753:Interleukin-10; D020780:Matrix Metalloproteinase 9