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

G. W. Volcheck, P. Kelkar, K. R. Bartemes, G. J. Gleich, Hirohito Kita

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1341-1346
Number of pages6
JournalClinical and Experimental Allergy
Volume35
Issue number10
DOIs
StatePublished - Oct 2005

Fingerprint

Adrenergic Agonists
Albuterol
Interleukin-5
Eosinophils
Superoxides
Cyclic AMP
Adrenergic Antagonists
Phosphodiesterase Inhibitors
Cytochromes c
Adrenergic Receptors
Anti-Inflammatory Agents
Asthma

Keywords

  • β-agonist
  • Albuterol
  • Asthma
  • Eosinophils
  • IL-5
  • Inflammation
  • Isomer
  • Superoxide

ASJC Scopus subject areas

  • Immunology

Cite this

Effects of (R)- and (S)-isomers of β-adrenergic agonists on eosinophil response to interleukin-5. / Volcheck, G. W.; Kelkar, P.; Bartemes, K. R.; Gleich, G. J.; Kita, Hirohito.

In: Clinical and Experimental Allergy, Vol. 35, No. 10, 10.2005, p. 1341-1346.

Research output: Contribution to journalArticle

Volcheck, G. W. ; Kelkar, P. ; Bartemes, K. R. ; Gleich, G. J. ; Kita, Hirohito. / Effects of (R)- and (S)-isomers of β-adrenergic agonists on eosinophil response to interleukin-5. In: Clinical and Experimental Allergy. 2005 ; Vol. 35, No. 10. pp. 1341-1346.
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T1 - Effects of (R)- and (S)-isomers of β-adrenergic agonists on eosinophil response to interleukin-5

AU - Volcheck, G. W.

AU - Kelkar, P.

AU - Bartemes, K. R.

AU - Gleich, G. J.

AU - Kita, Hirohito

PY - 2005/10

Y1 - 2005/10

N2 - 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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