title: Anti-inflammatory effects of clarithromycin in ventilator-induced lung injury.
abstract: BACKGROUND
  Mechanical ventilation can promote lung injury by triggering a pro-inflammatory response. Macrolides may exert some immunomodulatory effects and have shown significant benefits over other antibiotics in ventilated patients. We hypothesized that macrolides could decrease ventilator-induced lung injury.
  
  
  METHODS
  Adult mice were treated with vehicle, clarithromycin or levofloxacin, and randomized to receive mechanical ventilation with low (12 cmH2O, PEEP 2 cmH2O) or high (20 cmH2O, ZEEP) inspiratory pressures for 150 minutes. Histological lung injury, neutrophil infiltration, inflammatory mediators (NFκB activation, Cxcl2, IL-10) and levels of adhesion molecules (E-selectin, ICAM) and proteases (MMP-9 and MMP-2) were analyzed.
  
  
  RESULTS
  There were no differences among groups after low-pressure ventilation. Clarithromycin significantly decreased lung injury score and neutrophil count, compared to vehicle or levofloxacin, after high-pressure ventilation. Cxcl2 expression and MMP-2 and MMP-9 levels increased and IL-10 decreased after injurious ventilation, with no significant differences among treatment groups. Both clarithromycin and levofloxacin dampened the increase in NFκB activation observed in non-treated animals submitted to injurious ventilation. E-selectin levels increased after high pressure ventilation in vehicle- and levofloxacin-treated mice, but not in those receiving clarithromycin.
  
  
  CONCLUSIONS
  Clarithromycin ameliorates ventilator-induced lung injury and decreases neutrophil recruitment into the alveolar spaces. This could explain the advantages of macrolides in patients with acute lung injury and mechanical ventilation.
authors.forename: Laura
authors.initials: L
authors.lastname: Amado-Rodríguez
authors.forename: Adrián
authors.initials: A
authors.lastname: González-López
authors.forename: Inés
authors.initials: I
authors.lastname: López-Alonso
authors.forename: Alina
authors.initials: A
authors.lastname: Aguirre
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.forename: Estefanía
authors.initials: E
authors.lastname: Batalla-Solís
authors.forename: Jorge
authors.initials: J
authors.lastname: Blazquez-Prieto
authors.forename: Emilio
authors.initials: E
authors.lastname: García-Prieto
authors.forename: Guillermo M
authors.initials: GM
authors.lastname: Albaiceta
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017291:Clarithromycin / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D064704:Levofloxacin / Q000627:therapeutic use; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D055397:Ventilator-Induced Lung Injury / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D064704:Levofloxacin; D017291:Clarithromycin