Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA076

Poster Communications

Effects of olprinone on airway reactivity and inflammation in ovalbumin-sensitized guinea pigs

J. Mokrý1,2, M. Kertys1, A. Urbanova2,1, P. Kosutova2,3, D. Mokra3,2

1. Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, SR, Slovakia. 2. Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. 3. Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.


The effectiveness of selective phosphodiesterase (PDE) 4 inhibitors, e.g. roflumilast, has been confirmed previously in chronic obstructive pulmonary disease associated with neutrophil as well as eosinophilic inflammation. As the selective inhibition of PDE3 (present predominantly in airway smooth muscle and responsible for degradation of cAMP and cGMP), the aim of this study was to evaluate effects of olprinone (selective PDE3 inhibitor) in two different doses and dosing regimens on in vivo and in vitro airway smooth muscle reactivity to histamine, changes in blood cells count in blood and bronchoalveolar lavage (BAL) fluid, and some inflammatory mediators (interleukin (IL)-4 and IL-5) in ovalbumin sensitized guinea pigs with experimentally induced eosinophil inflammation (Mokry et al. 2017). Sensitized animals were administered 0.5 or 1.0 mg/kg b.w. of olprinone intraperitoneally as a single dose or once daily for 7 days. Sensitization with ovalbumin led to a significant increase in in vivo and in vitro airway reactivity (both p<0.01). Similarly, increased plasmatic levels of IL-4, and IL-5 in blood were observed (p<0.01), with significant increase in differential counts of eosinophils both in blood (p<0.05) and BAL fluid (p<0.01). The administration of olprinone suppressed significantly in vivo airway reactivity to histamine (p<0.01), and in vitro airway reactivity in tracheal tissue strips to cumulative doses of histamine (p<0.05). However, the IL-4 and IL-5 levels and changes in relative counts of inflammatory cells were only mild (p>0.05), suggesting that PDE3 inhibition has preferentially bronchorelaxing effects over anti-inflammatory action in guinea pigs with ovalbumin induced eosinophil inflammation. Inhibition of PDE3 could be considered as a potentially useful therapeutic tool for bronchodilation in obstructive airways diseases associated with allergic inflammation.

Where applicable, experiments conform with Society ethical requirements