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

Kenji Kuwabara, Shingo Furue, Yasuhiko Tomita, Masahiko Ueno, Takashi Ono, Akihiro Matsukawa, Masaru Yoshinaga, Katsuya Mikawa, Kahoru Nishina, Makoto Shiga, Hidefumi Obara, Yozo Hori

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13 Citations (Scopus)

Abstract

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 A2 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 A2 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 A2 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 A2 activity and the surfactant degradation in the lung, which might also account for its clinical ineffectiveness against early acute respiratory distress syndrome.

Original languageEnglish
Pages (from-to)209-216
Number of pages8
JournalEuropean Journal of Pharmacology
Volume433
Issue number2-3
DOIs
Publication statusPublished - Dec 21 2001
Externally publishedYes

Keywords

  • Acute
  • Lung injury
  • Methylprednisolone
  • Oleic acid
  • Secretory phospholipase A
  • Surfactant

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Kuwabara, K., Furue, S., Tomita, Y., Ueno, M., Ono, T., Matsukawa, A., Yoshinaga, M., Mikawa, K., Nishina, K., Shiga, M., Obara, H., & Hori, Y. (2001). Effect of methylprednisolone on phospholipase A2 activity and lung surfactant degradation in acute lung injury in rabbits. European Journal of Pharmacology, 433(2-3), 209-216. https://doi.org/10.1016/S0014-2999(01)01507-2