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

摘要

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 (PC_(150)) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed. Results The cough frequency per 3 minutes and PC_(150) in the challenge group were (22 +-4) times/3 minutes and (198 +-54) ug/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 PC_(150) 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) x10~6/ml and (20 +-5)% respectively, which were significantly different from (3. 2 +-0. 5) x10~6/ml and (29 +-5)% in the aminophylline group (P < 0. 05, respectively) or (4. 2 +-0. 7) x10~6/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.