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Effects of phosphodiesterase 4 inhibitor on cough response in guinea pigs sensitized and challenged with ovalbumin

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Author:
No author available
Journal Title:
CHINESE MEDICAL JOURNAL
Issue:
11
DOI:
No doi available
Key Word:
phosphodiesterase inhibitor;airway responsiveness;eosinophilic airway inflammation

Abstract: Background There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin. Methods Forty sensitized guinea pigs were randomly divided into four groups: control (n=10), challenge (n=10), SB207499 (n=10) and aminophylline (n=10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed. Results The cough frequency per 3 minutes and PC150 in the challenge group were (22±4) times/3 minutes and (198±54) μg/ml, which were significantly different from (6±2) times/3 minutes and (691±81) μg/ml in the control group (P<0.05, respectively). The injection of 25 mg/kg SB207499 significantly inhibited the increased cough response and airway hyperresponsiveness, the cough frequency and PC150 in guinea pigs were (13±2) times/3 minutes and (680±81) μg/ml (P<0.05), which differed significantly from (18±2) times/3 minutes and (400±86) μg/ml after the administration of the same dose of aminophylline (P<0.05). The inhibition of SB207499 on cough response was dose-dependent. Similarly, SB207499 decreased the total cell number and percentage of eosinophils in bronchoalveolar lavage fluid to (2.1±0.5)×106/ml and (20±5)% respectively, which were significantly different from (3.2±0.5)×106/ml and (29±5)% in the aminophylline group (P<0.05, respectively) or (4.2±0.7)×106/ml and (35±4)% in the challenge group (P<0.05, respectively). Conclusion Phosphodiesterase 4 inhibitor may be more useful than aminophylline for cough associated with eosinophilic airway inflammation via inhibiting airway inflammation and airway hyperresponsiveness.

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