An in vivo mouse model of allergic
bronchial asthma was developed to investigate the effects of a
platelet activating factor antagonist
ONO-6240 on eosinophil (EOS) recruitment into the mouse airway. In the present study, no EOS could be found in bronchoalveolar lavage fluid (BALF) from normal control mice. However, chronic
ovalbumin challenge of sensitized mice induced significant bronchoalveolar
eosinophilia (9.68 +/- 0.72 x 10(8)/L). In three groups of mice treated intraperitoneally with different doses of
ONO-6240 (0.1, 1.0, 10.0 mg/kg), the medication produced 42.1% (5.60 +/- 0.97 x 10(8)/L, P < 0.01), 58.8% (3.99 +/- 0.84 x 10(8)/L, P < 0.01), and 72.6% (2.65 +/- 0.71 x 10(8)/L, P < 0.01) inhibition, respectively, of the
antigen-induced influx of EOS into BALF. It was found that the prevention of EOS infiltration into airway with
ONO-6240 was accompanied by decrements of both
interleukin (IL)-5 and
IL-2 levels. These data indicated that
ONO-6240 prevented airway
eosinophilia by inhibiting production of
IL-5 and
IL-2. Our results suggested that
ONO-6240 may be of value in treating human asthmatic patients.