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Journal of Medical Sciences
Year: 2010  |  Volume: 10  |  Issue: 3  |  Page No.: 59 - 65

Effect of Theophylline and Cyclic AMP Analogue 8-Br-cAMP on Dermatophagoides Farinae induced IL-5 mRNA of Peripheral Blood Mononuclear Cells

T.P. Markova, Y. Aragane, A. Niwa, M. Tabuchi, M. Orita, K. Ooshima and H. Higashino    

Abstract: Phosphodiesterases (PDE) catalyze the breakdown of cAMP and thus, may have potent immunomodulatory activity. Theophyllin is a non-selective PDE inhibitor and has long been used to treat atopic diseases such as asthma, based on its well-known effects of the bronchodilative and anti-inflammatory effects, although the immune modulatory activities are not completely clear yet. Because it is believed that Th2-immnuity plays a pathogenic role in asthma, we were interested to study the mechanisms of how it modulates mite-allergen-induced activation of Th2-like immunity. To address this issue, peripheral blood mononuclear cells (PBMC) were prepared from human healthy volunteers, stimulated with mite-allergen dermatophagoides farinae (Der-f), RNA prepared and semi-quantitative RT-PCR was performed using primers specific for IL-5, a representative Th2 cytokine. Consequently, it was found that theophylline at a concentration of 10-6 to 10-5 M significantly downregulated Der-f-induced expression of IL-5 mRNA. Intriguingly, theophylline (10-5 M) inhibited the expression of IL-5 mRNA of PBMCs from patients allergic to house dust mite. To further explore the mechanisms involved, a PKA type I inhibitor Rp-8-Br-cAMPS was added, resulting in restoration of theophylline-downregulated expression of Der-f-induced IL-5 mRNA, indicating the involvement of PKA in this event. Together, the present study demonstrates that theophylline prevents allergen-induced PKA activation and thus may, at least in part, inhibit Th2-like immune responses.

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