RAPAMYCIN INHIBITS AIRWAY LEUKOCYTE INFILTRATION AND HYPERREACTIVITY IN GUINEA-PIGS

The effect of rapamycin on cell infiltration to the lung and on bronch ial hyperreactivity induced by an intravenous injection of sephadex be ads to guinea pigs was investigated. One day following the injection o f sephadex the total cell number in bronchoalveolar lavage (BAL) fluid was significantly increased from 24.77 to 83.45 x 10(6) cells. This w as reflected in an increase in eosinophils, neutrophils, macrophages a nd lymphocytes. In addition, there was an increase in the reactivity o f isolated bronchial strips to histamine. Rapamycin (5 mg/kg), adminis tered two hours before the injection of sephadex, reduced the eosinoph il, neutrophil, lymphocyte and macrophage number by 64%, 55%, 50% and 19%, respectively, and also inhibited the increased reactivity of isol ated bronchial strips to histamine. These results suggest that rapamyc in may reduce bronchial reactivity by the inhibition of leukocyte migr ation into the airways.