Comparison of the Effects of Selective and Non-selective Beta-adrenoreceptor Agonists on the Pro-inflammatory Activities of Human Neutrophils in Vitro

The objective of this study was to measure and compare the effects of 4 selective (fenoterol, formoterol, salbutamol, salmeterol) and 3 non-selective (epinephrine, norepinephrine, isoproterenol), -adrenoreceptor agonists, at a fixed, final concentration of 1 M, on intracellular cyclic AMP levels in human neutrophils in vitro and to relate alterations in these to the effects of the test agents on the production of superoxide and release of elastase following activation of the cells with the chemoattractant, FMLP. Intracellular cAMP was measured by radioimmunoassay, while superoxide and elastase were assayed using lucigenin-enhanced chemiluminescence and colorimetric procedures respectively. Of the 7 agents tested, fenoterol, formoterol, epinephrine and isoproterenol caused a substantial increase in neutrophil cAMP levels, which correlated well with the inhibitory effects of these agents on superoxide production and elastase release. The other agents were either inactive (salmeterol), or weakly active (norepinephrine, salbutamol). Pretreatment of neutrophils with the non-selective -adrenoreceptor blockading agent, propranolol (2 M), attenuated the cAMP-mediated, anti-inflammatory interactions of formoterol, epinephrine and isoproterenol with neutrophils, while atenolol, a selective ₁-blockading agent, as well as ₁- and ₂-adrenoreceptor antagonists were ineffective. These findings demonstrate that some, but not all, currently used -agonists suppress the proinflammatory activity of human neutrophils through interaction with ₂-adrenoreceptors on these cells and activation of adenylyl cyclase. If operative in vivo, these anti-inflammatory properties may contribute, albeit in a secondary manner, to the therapeutic activity of fenoterol, formoterol, epinephrine and isoproterenol.