Effects of phosphodiesterase inhibitors on interleukin-4 and interleukin-13 generation from human basophils

Authors

  • Nahid Eskandari,

    1. Academic Unit of Molecular Pharmacology and Pharmacogenetics, University of Sheffield, The Royal Hallamshire Hospital (Floor L), Sheffield S10 2JF
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  • Thulani Wickramasinghe,

    1. Academic Unit of Molecular Pharmacology and Pharmacogenetics, University of Sheffield, The Royal Hallamshire Hospital (Floor L), Sheffield S10 2JF
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  • Peter T Peachell

    Corresponding author
    1. Academic Unit of Molecular Pharmacology and Pharmacogenetics, University of Sheffield, The Royal Hallamshire Hospital (Floor L), Sheffield S10 2JF
      Academic Unit of Molecular Pharmacology and Pharmacogenetics, University of Sheffield, The Royal Hallamshire Hospital (Floor L), Sheffield S10 2JF. E-mail: p.t.peachell@shef.ac.uk
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Academic Unit of Molecular Pharmacology and Pharmacogenetics, University of Sheffield, The Royal Hallamshire Hospital (Floor L), Sheffield S10 2JF. E-mail: p.t.peachell@shef.ac.uk

Abstract

  • The aim of the present study was to determine whether inhibition of cyclic nucleotide phosphodiesterase (PDE) modulates the stimulated generation of the cytokines, interleukin-4 (IL-4) and IL-13, from human basophils. This was addressed by evaluating the effects of both nonselective and selective inhibitors of PDEs on the generation of cytokines from basophils.

  • The nonselective PDE inhibitors, isobutyl-methylxanthine (IBMX) and theophylline, attenuated the IgE-mediated generation of IL-4 and IL-13 and, also, the release of histamine from basophils.

  • The effects of the isoform-selective inhibitors, 8-methoxymethyl-IBMX (PDE 1 inhibitor), siguazodan (PDE3 inhibitor), rolipram (PDE4 inhibitor), denbufylline (PDE4 inhibitor), Org 30029 (mixed PDE3 and 4 inhibitor) and zaprinast (PDE5 inhibitor), were studied. Of these selective compounds, only rolipram, denbufylline and Org 30029 inhibited the IgE-dependent generation of IL-4, IL-13 and histamine from basophils to a statistically significant (P<0.05) degree.

  • The effects of isoform-selective inhibitors on basophils activated by IL-3 were evaluated. The IL-3-induced generation of IL-4, IL-13 and histamine was inhibited to a statistically significant (P<0.05) extent, only by compounds that act as inhibitors of PDE4.

  • These data suggest that inhibition of PDE4 can regulate the generation of cytokines from human basophils.

British Journal of Pharmacology (2004) 142, 1265–1272. doi:10.1038/sj.bjp.0705892

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