Dissociation of airway hyperresponsiveness from immunoglobulin E and airway eosinophilia in a murine model of allergic asthma

Nonspecific airway hyperresponsiveness (AHR) is a hallmark of human asthma, Both airway eosinophilia and high serum levels of total and antigen-specif ic immunoglobulin E (IgE) are associated with AHR. It is unclear, however, whether either eosinophilia or increased IgE levels contribute directly to, or predict, the development of AHR. Investigations conducted with various murine models of asthma and different mouse strains have resulted in confli cting evidence about the roles that IgE and airway eosinophilia play in the manifestation of AHR. We show that systemic priming with ovalbumin (OVA) i n alum, followed by a single day of OVA aerosol challenge, is sufficient to induce AHR, as measured by increased pulmonary resistance in response to i ntravenously delivered methacholine in BALB/c, but not C57BL/6 or B(6)D(2)F 1, mice. This was observed despite the fact that OVA-challenged BALB/c mice had less airway eosinophilia and smaller increases in total IgE than eithe r C57BL/G or B(6)D(2)F1 mice, and had less pulmonary inflammation and OVA-s pecific IgE than B(6)D(2)F1 mice. We conclude that airway eosinophilia, pul monary inflammation, and high serum levels of total or OVA-specific IgE are all insufficient to induce AHR in C57BL/6 and B(6)D(2)F1 mice, whereas BAL B/c mice demonstrate AHR in the absence of airway eosinophilia. These data confirm that the development of AHR is genetically determined, not only in naive mice, but also in actively immunized ones, and cannot be predicted by levels of airway eosinophilia, pulmonary inflammation, total IgE, or antig en-specific IgE.