Effects of carbocysteine on antigen-induced increases in cough sensitivity and bronchial responsiveness in guinea pigs.
Carbocysteine is a mucoactive drug and is being used for both acute and chronic infectious airway diseases. Although carbocysteine can repair the damage of epithelial cells caused by exposure to various agents, the effects of this agent on allergic airway diseases such as asthma and eosinophilic bronchitis with an isolated chronic cough, in both of which epithelial damage may be characteristic, is not clear. We investigated the effects of carbocysteine on antigen-induced cough hypersensitivity to inhaled capsaicin at 48 h and bronchial hyperresponsiveness to inhaled methacholine at 72 h after challenge with an aerosolized antigen in actively sensitized guinea pigs. After measuring bronchial responsiveness, we examined neutral endopeptidase (NEP) activity in the tracheal tissue. Carbocysteine (10, 30, or 100 mg/kg) was given intraperitoneally every 12 h for 3 days after antigen challenge. The number of coughs elicited by an aerosol of capsaicin (10(-4) M) was significantly (p < 0.01) decreased in carbocysteine groups (6.13 +/- 0.59 at 10 mg/kg, 4.88 +/- 0.67 at 30 mg/kg, and 4.50 +/- 0.33 at 100 mg/kg during 3 min measurement) compared with the control group (9.75 +/- 0.53). Furthermore, carbocysteine dose dependently repaired the antigen-induced decrease of NEP activity in the tracheal tissue, but it did not influence the bronchial hyperresponsiveness or bronchoalveolar lavage cell component. These findings suggest that carbocysteine promotes the repair of damaged epithelium by allergic reaction and may be useful in allergic airway diseases accompanied by isolated chronic coughing, especially eosinophilic bronchitis without asthma and tracheobronchitis with cough hypersensitivity.
Katayama
N
N
The Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan. katabon@skyblue.ocn.ne.jp
Fujimura
M
M
Ueda
A
A
Kita
T
T
Abo
M
M
Tachibana
H
H
Myou
S
S
Kurashima
K
K
D000280:Administration, Inhalation; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002211:Capsaicin / Q000008:administration & dosage* / Q000276:immunology; D002233:Carbocysteine / Q000008:administration & dosage*; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D015260:Neprilysin / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000201:enzymology
D000941:Antigens; D016210:Methacholine Chloride; D002233:Carbocysteine; D015260:Neprilysin; D002211:Capsaicin