Effects of phosphodiesterase inhibitors on interleukin-4 and interleukin-13 generation from human basophils.
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.
Eskandari
Nahid
N
Academic Unit of Molecular Pharmacology and Pharmacogenetics, University of Sheffield, Royal Hallamshire Hospital (Floor L), Sheffield S10 2JF.
Wickramasinghe
Thulani
T
Peachell
Peter T
PT
D001491:Basophils / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*
D018793:Interleukin-13; D010726:Phosphodiesterase Inhibitors; D015847:Interleukin-4