Damage of alveolar-capillary barrier, inflammation, oxidative
injury, and lung cell apoptosis represent the key features of acute
lung injury (ALI). This study evaluated if selective
phosphodiesterase (PDE)-4 inhibitor roflumilast can reduce the
mentioned changes in lavage-induced model of ALI. Rabbits with
ALI were divided into 2 groups: ALI without therapy (A group)
and ALI treated with roflumilast i.v. (1 mg/kg; A+R group). One
group of healthy animals without ALI served as ventilated
controls (C group). All animals were oxygen-ventilated for further
4 h. At the end of experiment, total and differential counts of
cells in bronchoalveolar lavage fluid (BALF) and total and
differential counts of white blood cells were estimated. Lung
edema formation was assessed from determination of protein
content in BALF. Pro-inflammatory cytokines (TNFα, IL-6 and
IL-8) and markers of oxidation (3-nitrotyrosine, thiobarbituricacid reactive substances) were detected in the lung tissue and
plasma. Apoptosis of lung cells was investigated
immunohistochemically. Treatment with roflumilast reduced leak
of cells, particularly of neutrophils, into the lung, decreased
concentrations of cytokines and oxidative products in the lung
and plasma, and reduced lung cell apoptosis and edema
formation. Concluding, PDE4 inhibitor roflumilast showed potent
anti-inflammatory actions in this model of ALI.