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

Abstract

BackgroundMechanical 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.MethodsAdult 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.ResultsThere 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.ConclusionsClarithromycin 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.

Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum

“…The beneficial effects of fidaxomicin in CDI and the ability of other macrolides to possess anti-inflammatory responses in nongastrointestinal organs (14,15) led us to hypothesize that fidaxomicin may affect inflammatory responses against C. difficile toxin A by modulating signaling pathways that regulate the mucosal inflammation activated by this toxin. We were unable to test the ability of these drugs to inhibit the effects of toxin B in ileal loops in vivo, .…”

“…It has been reported that several 14-or 15-membered antibiotic macrolides, such as clarithromycin and azithromycin, which inhibit bacterial ribosome activity, possess anti-inflammatory effects (14,15). Other, nonantibiotic macrolides, including tacrolimus and sirolimus, are used predominantly as immunomodulators.…”

Recent advances in our understanding of Streptococcus pneumoniae infection

“…These effects appear to be achieved via interference with mechanisms involved in the transcription of genes encoding these pro-inflammatory proteins [40-43]. …”

Lung inflammatory pattern and antibiotic treatment in pneumonia

“…Sanz et al [ 30 ], reported in respect of an animal study in vivo that erythromycin exerts anti-inflammatory activity and inhibits leukocyte recruitment in the lung. In in vitro studies, results suggest that macrolides exhibit a suppressive effect on cytokines in models of acute inflammation [ 25 ], viral bronchiolitis [ 31 ] and ventilator-induced lung injury [ 32 ]. Anderson et al [ 33 ], have reported that the production of pneumolysin, a key virulence factor of the pneumococcus, is attenuated by exposure of this microbial pathogen to clarithromycin.…”