Dexamethasone reduces lung inflammation induced by alveolar stretch in mice

Abstract

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 cmH₂O (“low” tidal volumes (V_T) ∼7.5 ml/kg; LV_T) or 18 cmH₂O (“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<0.05). BALf neutrophil numbers and inflammatory mediator expression (KC, IL-1β, IL-6, E-selectin) were enhanced in HV_T-ventilated mice compared to LV_T-ventilated mice (p<0.05). Dexamethasone inhibited lung inflammation caused by LV_T or HV_T-ventilation (p<0.05).

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.