Inhaled roflumilast and tadalafil supress airway reactivity and inflammation in ovalbumin-sensitized guinea pigs
Abstract
Introduction: Phosphodiesterases (PDEs) are enzymes involved in degradation of cAMP and cGMP. The clinical effectiveness of selective PDE4 inhibitors has been confirmed previously in chronic obstructive pulmonary disease associated with neutrophil inflammation. The aim of this study was to evaluate effects of roflumilast (selective PDE4 inhibitor) and tadalafil (selective PDE5 inhibitor) on in vivo and in vitro airway smooth muscle reactivity to histamine, changes in blood cells count in blood and bronchoalveolar lavage fluid, and some inflammatory mediators (IL-4 and IL-5) in ovalbumin sensitized guinea pigs with experimentally induced eosinophil inflammation. Sensitized animals were exposed to aerosol of roflumilast, tadalafil, or both for 3 minutes once daily for 7 days. Sensitization with ovalbumin led to a significant increase in in vivo and in vitro airway reactivity. Similarly, increased plasmatic levels of IL-4, and IL-5 in blood were observed, with significant increase in differential counts of eosinophils both in blood and BAL fluid. The administration of roflumilast and tadalafil suppressed significantly in vivo airway reactivity, in vitro airway reactivity in tracheal tissue strips, and IL-4 and IL-5 levels, suggesting that PDE4 and PDE5 inhibition has potent anti-inflammatory effects in guinea pigs with ovalbumin induced eosinophil inflammation. This work was supported by the project „Biomedical Center Martin“ ITMS code: 26220220187, the project is co-financed…
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