Additive effects of phosphodiesterase-4 inhibition on effects of rSP-C surfactant

We have tested the effects of combined treatment with a recombinant surfact ant protein C based surfactant (rSP-C surfactant) containing a phosphodiest erase-4 (PDE-4) inhibitor, roflumilast, in a lung lavage model of acute lun g injury. The following groups were tested: (1) controls receiving sham exp osure; (2) PDE-4 inhibitor (6.0 mg/kg body weight, intratracheally) alone; (3, 4) rSP-C surfactant (25 and 100 mg phospholipids [PL] per kg body weigh t) atone; and (5, 6) treatment with rSP-C surfactant (25 and 100 mg PL per kg body weight) combined with the PDE-4 inhibitor at a dose of 6.0 mg/kg bo dy weight. The different groups were compared with respect to improving oxy genation and histopathologic changes, e.g., hyaline membrane (HM) formation . Both doses of rSP-C surfactant improved oxygenation while even this high dose of the PDE-4 inhibitor alone did not influence oxygenation compared wi th untreated control animals. Addition of the PDE-4 inhibitor led to improv ed oxygenation based on both doses of rSP-C surfactant. The PDE-4 inhibitor atone prevented further HM formation and infiltration of neutrophil leukoc ytes. The rSP-C surfactant was able to prevent further HM formation. Based on both doses of rSP-C surfactant, addition of the PDE-4 inhibitor showed a dditional effects on oxygenation and inhibition of HM formation. The effect s of combined treatment were superior to each treatment alone, leading to t he conclusion that a rSP-C surfactant containing a PDE-4 inhibitor may act synergistically in this animal model of acute lung injury. We conclude that combined treatment with rSP-C surfactant and a PDE-4 inhibitor may be an e ffective treatment for patients with acute lung injury.