Inhibition of in vitro neutrophil migration through a bilayer of endothelial and epithelial cells using beta2-agonists: concomitant effects on IL-8 and elastase secretion and impact of glucocorticosteroids

Pulm Pharmacol Ther. 2005;18(5):354-62. doi: 10.1016/j.pupt.2005.01.006.

Abstract

Background: Beta2-agonists and glucocorticosteroids are two common treatments for COPD and they are often used in combination. Glucocorticosteroids mediate the anti-inflammatory response through the glucocorticosteroid receptors (GRs). Beta2-agonists are potent bronchodilators but they can have some anti-inflammatory properties by elevating the level of intracellular cAMP. In this study we aimed to investigate the anti-inflammatory effect of combination therapy in vitro.

Methods: Neutrophils or the bilayer of endothelial and epithelial cells were preincubated with salbutamol, budesonide or budesonide followed by salbutamol. FMLP-induced IL-8, elastase release and neutrophil migration through the bilayer was measured.

Results: Salbutamol at concentrations of 10(-4), 10(-5) and 10(-9) M inhibited IL-8, elastase release and migration of neutrophils in an inverse bell-shaped concentration-response manner. When given after budesonide (10(-9) and 10(-8)M), the inhibitory effect on migration was additive. This additive effect was not observed for elastase and IL-8 release.

Conclusions: Salbutamol inhibits neutrophil migration and IL-8 and elastase release in a concentration-dependent manner. Preincubation with low concentration of budesonide enhanced the inhibition of migration achieved by low concentrations of salbutamol.

MeSH terms

  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / administration & dosage
  • Albuterol / pharmacology*
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacology
  • Budesonide / administration & dosage
  • Budesonide / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Humans
  • Interleukin-8 / metabolism*
  • Neutrophil Infiltration / drug effects
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Pancreatic Elastase / metabolism*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / pathology

Substances

  • Adrenergic beta-Agonists
  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • Interleukin-8
  • Budesonide
  • Pancreatic Elastase
  • Albuterol