AIRWAY EOSINOPHILS, T-CELLS, TH2-TYPE CYTOKINE MESSENGER-RNA, AND HYPERREACTIVITY IN RESPONSE TO AEROSOL CHALLENGE OF ALLERGIC MICE WITH PREVIOUSLY ESTABLISHED PULMONARY INFLAMMATION

Asthma is characterized by acute episodes of nonspecific airway hyperr eactivity and chronic pulmonary inflammation exacerbated by stimuli in cluding allergen exposure. In order to reproduce the physiologic and i mmunologic responses that occur in asthmatic patients, we have charact erized a model of antigen-induced inflammation in which allergic mice (B6D2F1) that had been challenged once with aerosolized ovalbumin and had developed a pulmonary cellular infiltrate were rechallenged 1 wk l ater. Pulmonary inflammation in rechallenged mice was substantially gr eater than that in single-challenged mice. Eosinophils and activated-m emory T cells (CD44(+), CD45RB(lo)) in bronchoalveolar lavage (BAL) fl uid accumulated to higher levels and with faster kinetics in response to the second challenge than in response to the first challenge. Eosin ophils in lung tissue also accumulated to higher levels but with simil ar kinetics in response to the second challenge than in response to th e first challenge. Similarly, interleukin (IL)-4 and IL-5 steady-state mRNA levels in lung tissue increased after the second challenge and w ere higher than those measured after a single challenge. Furthermore, treatment of mice with an anti-IL-5 monoclonal antibody 2 h prior to r echallenge inhibited antigen induced eosinophil accumulation in the lu ngs. In mice challenged twice, peak in vivo bronchoconstrictor respons iveness to acetylcholine was increased following the second challenge compared with that observed following the initial challenge. In contra st, ex vivo tracheal smooth muscle contractile responsiveness to acety lcholine was not altered. Although mucus accumulation and epithelial d amage in pulmonary tissue were evident in mice challenged twice, these parameters were slightly reduced compared with those seen at similar times in mice challenged once. Therefore, although these mice exhibit only slight bronchial epithelial damage, the presence of significant i nflammation and airway hyperreactivity to acetylcholine as well as sli ghtly increased baseline reactivity demonstrate important similarities with the pathophysiology of asthma.