Glucocorticoids are the most potent and widely used
anti-inflammatory agents, but they are not particularly effective against early phase of
acute respiratory distress syndrome. We investigated whether
methylprednisolone, a synthetic
glucocorticoid, could inhibit increase of
phospholipase A(2) activity in the lung and lead to protection against a model of
acute respiratory distress syndrome in rabbits. Infusion of
oleic acid (0.1 ml/kg/h, i.v. for 2 h) provoked pulmonary
hemorrhage and
edema,
protein leakage and massive neutrophil infiltration, resulted in severe
hypoxemia and impaired lung compliance, accompanying the increase of
phospholipase A(2) activity and
interleukin-8, and degradation of
surfactant in the bronchoalveolar lavage fluid. Infusion of
methylprednisolone (60 mg/kg/h, i.v. for 30 min before the
oleic acid and then 0.5 mg/kg/h, i.v. for 6 h) did not improve the above described
lung injury induced by
oleic acid, nor did it suppress
phospholipase A(2) activity and degradation of
surfactant in bronchoalveolar lavage fluid, while it strongly reduced
interleukin-8 levels in both plasma and bronchoalveolar lavage fluid. We conclude that
methylprednisolone did not attenuate
oleic acid-induced
acute lung injury and this can be explained partly by its failure to reduce the increase of
phospholipase A(2) activity and the
surfactant degradation in the lung, which might also account for its clinical ineffectiveness against early
acute respiratory distress syndrome.