[Effects of a platelet-activating factor antagonist ONO-6240 on antigen induced eosinophil infiltration into the...

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.