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.[1]References
- Effects of phosphodiesterase inhibitors on interleukin-4 and interleukin-13 generation from human basophils. Eskandari, N., Wickramasinghe, T., Peachell, P.T. Br. J. Pharmacol. (2004) [Pubmed]
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