Dexamethasone reduces lung inflammation induced by alveolar stretch in mice

Background: Although mechanical ventilation is a lifesaving procedure, the associated alveolar stretch can provoke lung injury (ventilator-induced lung injury, VILI). At present, it is thought that ventilator-induced lung inflammation may precede lung injury. Activated granulocytes are known to induce oxidative stress and protease activity in alveoli, causing alveolar-capillary barrier disruption and lung dysfunction. Aim: To study the anti-inflammatory action of dexamethasone, a widely used glucocorticoid, in mice exposed to either low or high alveolar stretch. Methods: C57Bl6 mice were mechanically ventilated for 5 hours with either an inspiratory pressure of 10 cmH 2 O (“low” tidal volumes (V T ) ∼7.5 ml/kg; LV T ) or 18 cmH 2 O (“high” V T ∼15 ml/kg; HV T ). Dexamethasone was intravenously administered at initiation of ventilation. Non-ventilated mice served as controls. Inflammatory mediator expression and granulocyte influx were determined in lung homogenates. Differential cell counts were done on BALf cytospin preparations. Results: Both LV T and HV T -ventilation increased inflammatory mediator expression in lung tissue which was accompanied by granulocyte influx (p T -ventilated mice compared to LV T -ventilated mice (p T or HV T -ventilation (p Conclusion: Dexamethasone prevents inflammatory mediator expression and granulocyte influx in lungs of mice exposed to low or high alveolar stretch. Dexamethasone treatment may be considered as a potential therapeutic strategy to inhibit the inflammatory response during mechanical ventilation.