Anti-inflammatory effects of clarithromycin in ventilator-induced lung injury

Respir Res. 2013 May 10;14(1):52. doi: 10.1186/1465-9921-14-52.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Clarithromycin / therapeutic use*
  • Inflammation Mediators / blood
  • Levofloxacin / therapeutic use
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration / drug effects
  • Ventilator-Induced Lung Injury / drug therapy*
  • Ventilator-Induced Lung Injury / pathology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Inflammation Mediators
  • Levofloxacin
  • Clarithromycin