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

Respiratory Research

Guillermo M Albaiceta³  Emilio García-Prieto¹  Jorge Blazquez-Prieto⁴  Estefanía Batalla-Solís¹  Aurora Astudillo²  Alina Aguirre⁴  Inés López-Alonso⁴  Adrián González-López⁴  Laura Amado-Rodríguez¹ 

[1] Servicio de Medicina Intensiva, Hospital Universitario Central de Asturias, Oviedo, Spain;Departamento de Cirugía y Especialidades Médico-quirúrgicas, IUOPA, Universidad de Oviedo, Oviedo, Spain;CIBER-Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain;Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain

关键词: Neutrophil migration;    Macrolides;    E-selectin;    Mechanical ventilation;   

Others  :  794677
DOI  :  10.1186/1465-9921-14-52

 received in 2012-11-20, accepted in 2013-05-07,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Amado-Rodríguez et al.; licensee BioMed Central Ltd.

【 图 表 】

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