An animal model of late pulmonary responses to Alternaria challenge

The pathogenesis of the late asthmatic response to allergen inhalation is unknown; IgE as well as IgE- and IgG-dependent mechanisms have been proposed. This study was undertaken to determine whether rabbits immunized to produce only IgE to Alternaria tenius would develop immediate and late phase pulmonary responses to Alternaria aerosol challenge, and to compare this response in "IgE only" rabbits with the response in rabbits producing multiple antibody isotypes to the allergen. Neonatal rabbits immunized with Alternaria tenius extract produced only IgE to that allergen, whereas rabbits first immunized at 7 days of age made multiple antibody isotypes. After aerosol challenge, the rabbits with only IgE antibody to the Alternaria developed biphasic change in lung function, as assessed by changes in pulmonary resistance and dynamic compliance, whereas rabbits with anti-Alternaria IgG as well as IgE had blunted biphasic pulmonary responses. Intravenously administered isoproterenol did not reverse the late phase response. Transfusion with serum containing anti-Alternaria IgG into "IgE only" rabbits reduced both the early and late phase changes in pulmonary mechanics. Transfusion of plasma containing anti-Alternaria IgE into nonimmunized control rabbits produced, upon challenge, both early and late phase responses in pulmonary mechanics, which were lost in retesting 4 wk later. We conclude that in this system IgE-allergen interaction can result in both the immediate and late pulmonary responses, that the presence of IgG results in blunting rather than in enhancing of this responsiveness, and that the response can be seen in the absence of cellular immune mechanisms.