Effects of roflumilast, a phosphodiesterase-4 inhibitor, on the lung functions in a saline lavage-induced model of acute lung injury.

摘要

Acute lung injury (ALI) is associated with deterioration ofalveolar-capillary lining and transmigration and activation ofinflammatory cells. Whereas a selective phosphodiesterase-4(PDE4) inhibitor roflumilast has exerted potent anti-inflammatoryproperties, this study evaluated if its intravenous delivery caninfluence inflammation, edema formation, and respiratoryparameters in rabbits with a lavage-induced model of ALI. ALIwas induced by repetitive saline lung lavage (30 ml/kg). Animalswere divided into 3 groups: ALI without therapy (ALI), ALItreated with roflumilast i.v. (1 mg/kg; ALI+Rofl), and healthyventilated controls (Control), and were ventilated for following4 h. Respiratory parameters (blood gases, ventilatory pressures,lung compliance, oxygenation indexes etc.) were measured andcalculated regularly. At the end of experiment, animals wereoverdosed by anesthetics. Total and differential counts of cells inbronchoalveolar lavage fluid (BAL) were estimatedmicroscopically. Lung edema was expressed as wet/dry lungweight ratio. Treatment with roflumilast reduced leak of cells(P<0.01), particularly of neutrophils (P<0.001), into the lung,decreased lung edema formation (P<0.01), and improvedrespiratory parameters. Concluding, the results indicate a futurepotential of PDE4 inhibitors also in the therapy of ALI.