The inhaled administration of KF19514, a phosphodiesterase 4 and 1 inhibitor, prevents antigen-induced lung inflammation in guinea pigs.
We examined in this study the effect of KF19514, a phosphodiesterase 4 and 1 inhibitor, on antigen-induced lung inflammation by inhaled administration in guinea-pigs. It was previously reported that inhaled KF19514 prevented antigen-induced bronchoconstriction and platelet-activating factor (PAF)-induced lung inflammation. In fact, a variety of factors other than PAF are related to lung inflammation in real subjects with asthma. Guinea-pigs were actively sensitized by exposure to ovalbumin (OA). Fifteen to 20 days later, the guinea pigs were challenged by exposure to aerosols of five successively increasing concentrations of OA (0.01, 0.1, 0.5, 1 and 5 mg/ml). Bronchoalveolar lavages (BALs) were performed 24 h after the antigen challenge, and airway hyperresponsiveness to acetylcholine (ACh) was studied 24 h after the challenge by measuring lung resistance and dynamic compliance. Ovalbumin antigen challenge produced a marked and significant eosinophil accumulation in the BAL fluids and airway hyperresponsiveness to ACh 24 h after the challenge. Inhaled KF19514 (0.01-0.1%) inhibited the eosinophil accumulation significantly and dose-dependently but inhaled rolipram (0.01-0.1%) and aminophylline (0.1-1%) did not. In addition, the development of airway hyperresponsiveness was prevented by inhaled KF19514 (0.01%) but not by inhaled rolipram (0.01%) and aminophylline (0.1%). Based on these data, KF19514 was suggested to be a promising drug in the treatment of asthma by local administration to the lung.
Manabe
H
H
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co. Ltd, 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka, 411, Japan.
Akuta
K
K
Kawasaki
H
H
Ohmori
K
K
D000109:Acetylcholine; D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects*; D000628:Aminophylline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D009287:Naphthyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010972:Platelet Activating Factor; D011014:Pneumonia / Q000517:prevention & control; D020889:Rolipram / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D014665:Vasodilator Agents
D001993:Bronchodilator Agents; C106878:KF 19514; D009287:Naphthyridines; D010726:Phosphodiesterase Inhibitors; D010972:Platelet Activating Factor; D014665:Vasodilator Agents; D000628:Aminophylline; D020889:Rolipram; D000109:Acetylcholine