The beta-2-adrenoreceptor agonists, formoterol and indacaterol, but not salbutamol, effectively suppress the reactivity of human neutrophils in vitro

Mediators Inflamm. 2014;2014:105420. doi: 10.1155/2014/105420. Epub 2014 Mar 6.


The clinical relevance of the anti-inflammatory properties of beta-2 agonists remains contentious possibly due to differences in their molecular structures and agonist activities. The current study has compared the effects of 3 different categories of β 2-agonists, namely, salbutamol (short-acting), formoterol (long-acting) and indacaterol (ultra-long-acting), at concentrations of 1-1000 nM, with human blood neutrophils in vitro. Neutrophils were activated with either N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP, 1 µM) or platelet-activating factor (PAF, 200 nM) in the absence and presence of the β 2-agonists followed by measurement of the generation of reactive oxygen species and leukotriene B4, release of elastase, and expression of the β 2-integrin, CR3, using a combination of chemiluminescence, ELISA, colorimetric, and flow cytometric procedures respectively. These were correlated with alterations in the concentrations of intracellular cyclic-AMP and cytosolic Ca(2+). At the concentrations tested, formoterol and indacaterol caused equivalent, significant (P < 0.05 at 1-10 nM) dose-related inhibition of all of the pro-inflammatory activities tested, while salbutamol was much less effective (P < 0.05 at 100 nM and higher). Suppression of neutrophil reactivity was accompanied by elevations in intracellular cAMP and accelerated clearance of Ca(2+) from the cytosol of activated neutrophils. These findings demonstrate that β 2-agonists vary with respect to their suppressive effects on activated neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Antagonists / pharmacology*
  • Albuterol / pharmacology*
  • Calcium / metabolism
  • Cell Survival
  • Cyclic AMP / metabolism
  • Cytosol / metabolism
  • Ethanolamines / pharmacology*
  • Flow Cytometry
  • Formoterol Fumarate
  • Humans
  • Indans / pharmacology*
  • Leukotriene B4 / metabolism
  • Neutrophils / drug effects*
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Oxygen Consumption
  • Pancreatic Elastase / metabolism
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Quinolones / pharmacology*
  • Reactive Oxygen Species / metabolism


  • Adrenergic beta-2 Receptor Antagonists
  • Ethanolamines
  • Indans
  • Quinolones
  • Reactive Oxygen Species
  • Leukotriene B4
  • indacaterol
  • Cyclic AMP
  • Pancreatic Elastase
  • Albuterol
  • Calcium
  • Formoterol Fumarate