In vivo airway eosinophil accumulation induced by polymyxin-B reduces bronchial responsiveness in guinea pigs.
BACKGROUND
Chronic desquamative eosinophilic bronchitis and bronchial hyperresponsiveness have been considered essential for bronchial asthma. However, it has not been studied whether airway eosinophils enhance or inhibit bronchial responsiveness in vivo.


OBJECTIVE
This study was conducted to elucidate the influence of airway eosinophil accumulation on bronchial responsiveness in vivo.


METHODS
Guinea pigs were transnasally treated with 75 microg/kg of polymyxin-B or vehicle twice a week for a total of 3 weeks. Guinea pigs were surgically cannulated and artificially ventilated 24 h after the last administration of polymyxin-B or vehicle. Ten minutes after the installation of artificial ventilation, ascending doses of methacholine, acetylcholine or histamine were inhaled for 20 s at intervals of 5 min. Subsequent study was conducted 20 min after treatment of 60 mg/kg of indomethacin in the same manner. Final study was conducted in naive guinea pigs after single inhalation of 75 microg/mL of polymyxin B.


RESULTS
The proportion of eosinophils in bronchoalveolar lavage fluid significantly increased in guinea pigs treated with polymyxin-B compared with vehicle. Bronchial responsiveness to inhaled methacholine, acetylcholine and histamine was significantly decreased by the polymyxin-B treatment. This protective effect induced by polymyxin B was abolished by pretreatment of indomethacin. A significant increase in bronchial responsiveness was observed after a single inhalation of polymyxin B.


CONCLUSIONS
These results suggest that in vivo airway eosinophils may reduce non-specific bronchial responsiveness through inhibitory or bronchoprotective prostanoids.
Ishiura
Y
Y
Third Department of Internal Medicine, Kanazawa University School of Medicine, Takara-machi, Kanazawa, Japan. ishiura-@p2322nsk.ne.jp
Fujimura
M
M
Myou
S
S
Nobata
K
K
Liu
Q
Q
Yamamori
C
C
Amemiya
T
T
D000109:Acetylcholine / Q000008:administration & dosage; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D023421:Models, Animal; D011112:Polymyxin B / Q000008:administration & dosage* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D016210:Methacholine Chloride; D006632:Histamine; D011112:Polymyxin B; D000109:Acetylcholine; D007213:Indomethacin