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

Abstract

BACKGROUND:

Macrolides are antibiotics that have anti-inflammatory activities. 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 48h 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 12h 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 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.

• Authors: Akira Tokuda, Noriyuki Ohkura, Masaki Fujimura, Shiho Furusho, Miki Abo, Nobuyuki Katayama
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 23 Issue 1 Pg. 55-61 (Feb 2010) ISSN: 1522-9629 [Electronic] England
• PMID: 19835975 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Antigens
• Macrolides
• Leukotriene B4
• Substance P
• Erythromycin
• Dinoprostone

Topics

• Animals
• Anti-Bacterial Agents (therapeutic use)
• Antigens (immunology)
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Cough (drug therapy, physiopathology)
• Dinoprostone (analysis)
• Erythromycin (therapeutic use)
• Guinea Pigs
• Leukotriene B4 (analysis)
• Macrolides (therapeutic use)
• Male
• Reflex (drug effects)
• Substance P (analysis)