Effects of macrolides on antigen-induced increases in cough reflex sensitivity in guinea pigs

Abstract

Hence, they are used for both acute and chronic inflammatory airway diseases.However, the effects of these agents on allergic airway disorders presenting with an isolated chronic cough, such as non-asthmatic eosinophilic bronchitis and eosinophilic tracheobronchitis with cough hypersensitivity (atopic cough), still remain to be elucidated.Objective: To determine if macrolides are effective in the management of chronic cough caused by eosinophilic airway inflammation. Methods:The cough reflex sensitivity to inhaled capsaicin was measured at 48 h after challenge with an aerosolized antigen in actively sensitized guinea pigs.The 14-, 15-or 16-membered macrolides (erythromycin, azythromycin, or josamycin, respectively) were given intraperitoneally every 12 h after the antigen challenge. Bronchoalveolar lavage and the resection of the tracheal tissue were performed immediately after the measurement of the cough response to capsaicin. Results:The antigen-induced increase in the number of coughs elicited by capsaicin inhalation was significantly reduced by treatments with erythromycin and azythromycin, but not with josamycin. Erythromycin dose-dependently inhibited the increases in the substance P, prostaglandin E 2 and leukotriene B 4 levels, but not the histamine levels, in the bronchoalveolar lavage fluid. However, erythromycin did not influence the antigen-induced decrease in the neutral endopeptidase (NEP) activity in the tracheal tissue.Conclusions: Both 14-and 15-membered, but not 16-membered, macrolides 3 could reduce the antigen-induced cough reflex hypersensitivity by inhibiting the antigen-induced release of the afferent sensory nerve sensitizers. These macrolides may be therapeutically useful for the treatment of isolated chronic cough based on cough reflex hypersensitivity in allergic airway diseases such as non-asthmatic eosinophilic bronchitis and atopic cough.

Therapeutic effects of naringin in a guinea pig model of ovalbumin-induced cough-variant asthma

“…Several findings have suggested that the capsaicin-induced cough is mediated mainly by the activation of the transient receptor potential vanilloid type channel-1 (TRPV1), a capsaicin receptor on the terminal of the nonmyelinated C-fibers and thin myelinated Ad-fibers [30]. Several studies have also reported that immunosensitization may facilitate the release of tachykinins from C-fiber endings by the stimulation of capsaicin.…”