Pharmacological analysis of antigen-induced late airway response in rats.
The pharmacological and pathophysiological characteristics of rat antigen-induced late airway response (LAR) are not yet fully understood. In this study, the pharmacological properties of rat ovalbumin (OVA)-induced LAR and effects of the clinically used anti-asthmatic drugs salbutamol (beta2-agonist), ketotifen (antihistamine), pranlukast (anti-leukotriene C4/D4/E4), and prednisolone (steroid) were examined. In addition, a comparison was made of cell infiltration in bronchoalveolar lavage fluid (BALF) between immediate airway response (IAR) and LAR, and the edematous features of lung during LAR were also examined. Although infiltration of inflammatory cells into BALF was increased in both IAR and LAR, only the increase in eosinophils at 1, 3, and 6 h during LAR were significantly higher than those during IAR. Although beta2-agonist, antihistamine, and anti-leukotriene C4/D4/E4 exhibited no effects on rat LAR, steroid attenuated LAR and decreased eosinophil number in BALF. LAR and the percentage water content were both increased after antigen inhalation, suggesting that LAR is involved in pulmonary edema in rats. In conclusion, antigen-induced LAR was related to pulmonary edema and eosinophil infiltration rather than contraction of airway smooth muscle. This is the first comprehensive study of the profiles of rat antigen-induced LAR, and these analyses of LAR improve understanding of the diverse mechanisms underlying human asthmatic diseases.
Miyagawa
Naoki
N
Central Pharmaceutical Research Institute, Japan Tobacco, Inc., Osaka, Japan. naoki.miyagawa@ims.jti.co.jp
Iwasaki
Hidenori
H
Kato
Toshinobu
T
Tanaka
Masaru
M
Shibata
Tsutomu
T
Wakitani
Korekiyo
K
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002867:Chromones / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D007665:Ketotifen / Q000494:pharmacology; D007958:Leukocyte Count; D008297:Male; D010047:Ovalbumin / Q000276:immunology*; D011239:Prednisolone / Q000494:pharmacology; D011654:Pulmonary Edema / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
D018927:Anti-Asthmatic Agents; D002867:Chromones; D010047:Ovalbumin; D011239:Prednisolone; D000420:Albuterol; C047681:pranlukast; D007665:Ketotifen