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.
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.
Sadowska
A M
AM
Department of Respiratory Medicine, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. anna.sadowska@ua.ac.be
Manuel-y-Keenoy
B
B
De Backer
W A
WA
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000473:pathology
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D016209:Interleukin-8; D019819:Budesonide; D010196:Pancreatic Elastase; D000420:Albuterol