High-dose dexamethasone induced LPS-stimulated rat alveolar macrophages apoptosis

Drug Des Devel Ther. 2017 Oct 25:11:3097-3104. doi: 10.2147/DDDT.S147014. eCollection 2017.

Abstract

Prolonged administration of an excessive dose of corticosteroids proved to be harmful for patients with acute lung injury (ALI). A previous study has found that repeated administration of an excessive dose of methylprednisolone reduced alveolar macrophages (AMs) in bronchoalveolar lavage fluid (BALF) with an unknown mechanism. This study aimed to investigate the effect of excessive use of dexamethasone (Dex) on BALF AMs in vitro. Transmission electron microscopy and DNA fragmentation analysis demonstrated that 10-4 and 10-5 M Dex induced lipopolysaccharide-stimulated rat AMs apoptosis with downregulation of tumor necrosis factor-α, interleukin (IL)-12 and upregulation of IL-10, transforming growth factor-β. These results indicated that apoptosis might be a novel contribution involved in the detrimental effect of excessive dose of Dex clinically used to treat ALI.

Keywords: acute lung injury; alveolar macrophage; apoptosis; dexamethasone; inflammatory cytokines; lipopolysaccharide.

MeSH terms

  • Acute Lung Injury / drug therapy
  • Animals
  • Apoptosis / drug effects*
  • Bronchoalveolar Lavage Fluid
  • DNA Fragmentation / drug effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / toxicity*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / toxicity*
  • Interleukin-10 / genetics
  • Interleukin-12 / genetics
  • Lipopolysaccharides / pharmacology
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / pathology
  • Male
  • Microscopy, Electron, Transmission
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta / genetics
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Glucocorticoids
  • Lipopolysaccharides
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Dexamethasone