Effect of eotaxin and platelet-activating factor on airway inflammation and hyperresponsiveness in guinea pigs in vivo

Although eotaxin causes selective infiltration of eosinophils into the lung , its role in airway hyperresponsiveness remains unclear. We studied the ef fects of local administration of eotaxin on airway inflammation and hyperre sponsiveness in guinea pigs in vivo. Airway responsiveness to inhaled hista mine and differential cell counts in bronchoalveolar lavage fluid (BALF) we re evaluated 12 h, 24 h, 3 d, and 7 d after intratracheal instillation of e otaxin. Significant eosinophilia in BALF was observed between 6 h and 7 d a fter eotaxin administration. Histologically, eosinophil accumulation was ob served in the airways but not in the alveoli. In contrast, eotaxin did not affect airway responsiveness between 12 h and 7 d after its administration. We then studied the effects on airway responsiveness of subthreshold doses of interleukin 5, leukotriene D-4 (LTD4), and platelet-activating factor ( PAF) combined with eotaxin. Neither interleukin 5 nor LTD4 affected airway responsiveness. After eotaxin treatment, PAF significantly enhanced airway responsiveness without further increases in eosinophil counts. Eotaxin plus PAF significantly increased in eosinophil peroxidase activity in BALF comp ared with control and with eotaxin alone. These data indicate that eotaxin alone causes eosinophil accumulation in the airways but not hyperresponsive ness, and that additional factors such as PAF are needed to activate eosino phils for the development of airway hyperresponsiveness.