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

• Published in: Respiratory research 2013-05, Vol.14 (1), p.52-52, Article 52
• Main Authors: Amado-Rodríguez, Laura, González-López, Adrián, López-Alonso, Inés, Aguirre, Alina, Astudillo, Aurora, Batalla-Solís, Estefanía, Blazquez-Prieto, Jorge, García-Prieto, Emilio, Albaiceta, Guillermo M
• Format: Article
• Language: English
• Subjects: Acute respiratory distress syndrome; Animals; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antibiotics; Care and treatment; Clarithromycin; Clarithromycin - therapeutic use; Health aspects; High pressure; Inflammation Mediators - blood; Levofloxacin - therapeutic use; Lung - pathology; Lungs; Mice; Mice, Inbred C57BL; Mortality; Neutrophil Infiltration - drug effects; Proteins; Respiratory distress syndrome; Rodents; Ventilation; Ventilator-Induced Lung Injury - drug therapy; Ventilator-Induced Lung Injury - pathology; Ventilators
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/1465-9921-14-52

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. 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. 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. 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.