Effects of (R)- and (S)-isomers of β-adrenergic agonists on eosinophil response to interleukin-5

Authors

  • G. W. Volcheck,

    1. Department of Internal Medicine, Division of Allergic Diseases
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  • P. Kelkar,

    1. Department of Internal Medicine, Division of Allergic Diseases
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  • K. R. Bartemes,

    1. Department of Immunology, The Allergic Diseases Research Laboratory, Mayo Clinic and Foundation, Mayo Graduate School of Medicine, Rochester, MN, USA
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  • G. J. Gleich,

    1. Department of Internal Medicine, Division of Allergic Diseases
    2. Department of Immunology, The Allergic Diseases Research Laboratory, Mayo Clinic and Foundation, Mayo Graduate School of Medicine, Rochester, MN, USA
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    • 1Current address: Department of Dermatology, 4B454 School of Medicine, University of Utah, 30 North 1900 East, Salt Lake City, UT 84132-2049, USA.

  • H. Kita

    1. Department of Internal Medicine, Division of Allergic Diseases
    2. Department of Immunology, The Allergic Diseases Research Laboratory, Mayo Clinic and Foundation, Mayo Graduate School of Medicine, Rochester, MN, USA
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Hirohito Kita, Mayo Clinic Rochester, Rochester, MN 55905, USA. E-mail: kita.hirohito@mayo.edu.

Summary

Background Racemic β2-adrenergic receptor agonists (β2-agonists) are used frequently to treat patients with asthma. Potential differences in the biological activities and clinical efficacies among racemic β2-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 β2-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 β2-adrenergic receptor antagonist, ICI 118, 551, verifying the involvement of both cAMP and the β2-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.

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