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Systemic administration of E-selectin-directed dexamethasone liposomes attenuates pulmonary inflammation in a mouse model of ventilator-induced lung injury
Critical Care volume 13, Article number: P327 (2009)
Mechanical ventilation (MV) may evoke damage to healthy lungs leading to ventilator-induced lung injury (VILI). We hypothesized that downregulation of pulmonary inflammation may attenuate VILI. The present study investigated whether lung inflammation and injury can be restored by dexamethasone (Dex). To prevent the systemic negative side effects of free Dex, we targeted Dex by delivering anti-E-selectin Dex liposomes into activated endothelium of inflamed lungs.
Mice were tracheotomized and ventilated in the pressure control mode for 5 hours with 50% oxygen levels, 2 cmH2O positive end-expiratory pressure and 12 cmH2O peak inspiratory pressure (lung protective, LP-MV) or 20 cmH2O peak inspiratory pressure (lung injurious, LI-MV). Nonventilated mice were used as controls. Free Dex, anti-E-selectin or isotype IgG Dex liposomes were given systemically at initiation of MV. After 5 hours, lung injury was determined by arterial oxygen levels, tissue edema and bronchoalveolar lavage protein levels. Pulmonary inflammation was assessed by myeloperoxidase activity and IL-1β, keratinocyte-derived chemokine and E-selectin mRNA.
LI-MV decreased oxygenation levels, increased tissue edema and increased bronchoalveolar lavage protein levels as compared with LP-MV, suggesting that lung function was deteriorated by LI-MV. Both MV strategies enhanced pulmonary inflammation. Anti-E-selectin Dex liposomes and free Dex, but also IgG Dex liposomes, reduced ventilator-induced lung inflammation. However, Dex treatment did not diminish lung injury.
Systemic administration of targeted and free Dex attenuates VILI-associated pulmonary inflammation, but not lung injury.
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Hegeman, M., Cobelens, P., Hennus, M. et al. Systemic administration of E-selectin-directed dexamethasone liposomes attenuates pulmonary inflammation in a mouse model of ventilator-induced lung injury. Crit Care 13 (Suppl 1), P327 (2009). https://doi.org/10.1186/cc7491
- Mechanical Ventilation
- Lung Injury
- Lung Inflammation
- Pulmonary Inflammation
- Tissue Edema