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Effects of ( R )‐ and ( S )‐isomers of β‐adrenergic agonists on eosinophil response to interleukin‐5
Author(s) -
Volcheck G. W.,
Kelkar P.,
Bartemes K. R.,
Gleich G. J.,
Kita H.
Publication year - 2005
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2005.02347.x
Subject(s) - superoxide , ibmx , chemistry , pharmacology , phosphodiesterase inhibitor , phosphodiesterase , agonist , salbutamol , antagonist , receptor , endocrinology , medicine , biochemistry , biology , asthma , enzyme , forskolin
Summary Background Racemic β 2 ‐adrenergic receptor agonists (β 2 ‐agonists) are used frequently to treat patients with asthma. Potential differences in the biological activities and clinical efficacies among racemic β 2 ‐agonists and their isomers are controversial, and research into these possible differences is limited. Objective We hypothesized that the ( S )‐ and the ( R )‐isomers of β 2 ‐agonists have opposing effects on the activation of inflammatory cells. Methods Isolated human eosinophils were pretreated with 1 : 1 racemic ( R , S )‐, ( R )‐ or ( S )‐albuterol, isobutyl methylxanthine (IBMX), and stimulated with IL‐5. The kinetics of superoxide production were examined by reduction of cytochrome c , and the effects of pharmacological agents on superoxide production were monitored for 180 min. Results ( R , S )‐albuterol inhibited IL‐5‐induced superoxide production. This inhibition was enhanced by a cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor, IBMX, and was reversed by the selective β 2 ‐adrenergic receptor antagonist, ICI 118, 551, verifying the involvement of both cAMP and the β 2 ‐adrenergic receptor. In addition, ( R )‐albuterol alone, similarly to ( R , S )‐albuterol, significantly inhibited IL‐5‐induced superoxide production up to 60 min ( P <0.05, n =4), but the inhibition was lost with longer incubation. In contrast, ( S )‐albuterol with IBMX did not inhibit IL‐5‐induced superoxide production before 60 min, but it significantly enhanced IL‐5‐mediated superoxide production after 60 min ( P <0.05, n =4). When both were present as racemic ( R , S )‐albuterol, the inhibitory effect of ( R )‐albuterol was not affected by ( S )‐albuterol. Conclusion When incubated with IL‐5‐activated eosinophils, ( R )‐albuterol shows anti‐inflammatory effects and ( S )‐albuterol shows pro‐inflammatory effects in the presence of IBMX. The kinetics of these effects are different, and when used simultaneously, ( R )‐albuterol predominates. When marked usage of the ( S )‐isomer is anticipated, racemic ( R , S )‐albuterol should be used clinically with caution.