Effects of phosphodiesterase 4 inhibitor on cough response in guinea pigs sensitized and challenged with ovalbumin
Lü, H-Jing.; Qiu, Z-Min.; Wei, W-Li.; Yu, L.; Liu, R-Lin.; Zhang, M.
Chinese Medical Journal 117(11): 1620-1624
2004
ISSN/ISBN: 0366-6999 PMID: 15569475 Document Number: 570122
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) mug/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) mug/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) mug/ml (P < 0.05), which differed significantly from (18 +/- 2) times/3 minutes and (400 +/- 86) mug/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) x 106/ml and (20 +/- 5)% respectively, which were significantly different from (3.2 +/- 0.5) x 106/ml and (29 +/- 5)% in the aminophylline group (P < 0.05, respectively) or (4.2 +/- 0.7) x 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.