NOVEL ANIMAL-MODEL FOR INVESTIGATING PERSISTENT AIRWAY HYPERRESPONSIVENESS

The present study investigates the development and maintenance of airw ay hyperresponsiveness in neonatally immunized rabbits. Rabbits were i mmunized within 24 hr of birth with the antigen Alternaria tenuis toge ther with aluminum hydroxide as an adjuvant, followed by repeated anti gen and adjuvant administration up to 3 months of age. Anesthetized, s pontaneously breathing rabbits immunized according to this protocol ex hibited a 3.7- (p < 0.01) and 1.8-fold (p < 0.05) increase in airway r esponsiveness to inhaled histamine when compared with groups of naive or sham-immunized rabbits, respectively. In the absence of further ant igen challenge, these changes in airway responsiveness to histamine in a subpopulation of antigen-immunized rabbits persisted for up to 12 m onths of age. This hyperresponsiveness was not associated with an alte ration in either total or differential inflammatory cell numbers as as sessed by bronchoalveolar lavage (BAL), and no significant differences in isolated bronchial smooth muscle responsiveness to methacholine, h istamine, theophylline, or electrical field stimulation were observed. These results demonstrate that neonatal immunization of rabbits with Alternaria tenuis can lead to the development of persistent airway hyp erresponsiveness, and that the maintenance of this state is unrelated to either a detectable alteration in cellular infiltration within the airway lumen or changes in bronchial smooth muscle responsiveness. It is suggested that neonatal exposure to antigen and adjuvant may be imp ortant determinants for the development of persistent airway hyperresp onsiveness. This animal model may provide a useful way to investigate the effects of drugs on airway hyperresponsiveness.