Rapamycin inhibits airway leukocyte infiltration and hyperreactivity in guinea pigs

The effect of rapamycin on cell infiltration to the lung and on bronchial hyperreactivity induced by an intravenous injection of sephadex beads to guinea pigs was investigated. One day following the injection of sephadex the total cell number in bronchoalveolar lavage (BAL) fluid was significantly increased from 24.77 to 83.45 x 10(6) cells. This was reflected in an increase in eosinophils, neutrophils, macrophages and lymphocytes. In addition, there was an increase in the reactivity of isolated bronchial strips to histamine. Rapamycin (5 mg/kg), administered two hours before the injection of sephadex, reduced the eosinophil, neutrophil, lymphocyte and macrophage number by 64%, 55%, 50% and 19%, respectively, and also inhibited the increased reactivity of isolated bronchial strips to histamine. These results suggest that rapamycin may reduce bronchial reactivity by the inhibition of leukocyte migration into the airways.