Resolution of bronchial hyperresponsiveness and pulmonary inflammation is associated with IL-3 and tissue leukocyte apoptosis

We have used two models of murine pulmonary inflammation to investigate the signals responsible for the resolution of bronchial hyperresponsiveness (B HR), Both protocols involved two sensitizations with OVA followed by serial aerosolized challenge with OVA, We determined that administration of the s econd sensitization by aerosol (model A) was associated with a transient re sponse, whereas administration by the i.p. route (model B) induced a sustai ned response, in the form of BHR and eosinophilia, This difference in kinet ics was due solely to the route of the second Ag administration and was not associated with Ag dose or adjuvant, Differences in kinetics of lung eosin ophilia/BHR were shown to be independent of IgE levels and IL-4 or IL-5, Ho wever, IL-3 levels in model A closely correlated with the rate of leukocyte clearance by apoptosis and were observed concomitant with a decline in BHR , Blockage of IL-3 in model B increased leukocyte apoptosis but reduced tis sue eosinophilia and BHR, The use of mouse models in which a single differe nt administration of allergen is associated with a failure/success to resol ve inflammation and BHR by 72 h postchallenge indicates a link between IL-3 production, leukocyte apoptosis, and BHR responses.