Effects of Selective Inhibition of PDE4 by YM976 on Airway Reactivity and Cough in Ovalbumin-Sensitized Guinea Pigs
Phosphodiesterases (PDEs) are enzymes involved in the degradation of cAMP and cGMP. Selective PDE4 inhibitors (e.g., roflumilast) are effective in therapy of chronic obstructive pulmonary disease associated with neutrophil inflammation. The aim of this study was to evaluate the effects of a selective PDE4 inhibitor, YM976, on citric acid-induced cough, in vivo and in vitro airway smooth muscle reactivity to histamine, and on inflammatory mediators in ovalbumin-sensitized guinea pigs, with experimentally induced eosinophil inflammation. The YM976 was administered intraperitoneally at a dose of 1.0 mg/kg once daily for 7 days. Sensitization with ovalbumin led to a significant increase in the number of coughs, and in vivo and in vitro airway reactivity. Also, increased plasma levels of IL-4, IL-5, and PAF were observed, with a significant increase in the differential count of eosinophils in both blood and bronchoalveolar lavage fluid. The YM976 suppressed the number of coughs, the airway reactivity in tracheal tissue strips, and the IL-4 level. The findings indicate that PDE4 inhibition by YM976 exerts antitussive and anti-inflammatory effects in guinea pigs with ovalbumin-induced eosinophilic inflammation.
KeywordsAirway reactivity Animal model Citric acid Histamine Inflammation Interleukins Organ bath Phosphodiesterase inhibitors
We thank K. Jesenska for technical assistance. This study was supported in parts by VEGA grant 1/0260/14, Slovak Research and Development Agency under the contract no. APVV-0305-12, grant MZ2012/35-UKMA-12, and by the project “Biomedical Center Martin” ITMS code: 26220220187, the project is co-financed from EU sources.
Conflicts of Interest
The authors declare no conflicts of interest in relation to this article.
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