Effect of methylprednisolone on phospholipase A2 activity and lung surfactant degradation in acute lung injury in rabbits

Autor: Yasuhiko Tomita, Kahoru Nishina, Yozo Hori, Masahiko Ueno, Kenji Kuwabara, Takashi Ono, Katsuya Mikawa, Shingo Furue, Akihiro Matsukawa, Masaru Yoshinaga, Hidefumi Obara, Makoto Shiga
Rok vydání: 2001
Předmět:
Zdroj: European Journal of Pharmacology. 433:209-216
ISSN: 0014-2999
Popis: 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.
Databáze: OpenAIRE