AN ANIMAL-MODEL OF LATE PULMONARY RESPONSES TO ALTERNARIA CHALLENGE

Abstract

The pathogenesis of the late asthmatic response to allergen inhalation in unknown; IgE and IgE- and IgG-dependent mechanisms are proposed. A study was undertaken to determine whether rabbits immunized to produce only IgE to A. tenuis 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 A. 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 changes in lung function, as assessed by changes in pulmonary resistance and dynamic compliance, whereas rabbits with anti-Alternaria IgG and IgE had blunted biphasic pulmonary responses. Isoproterenol administered i.v. 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 challege, both early and late phase responses in pulmonary mechanics, which were lost in retesting 4 wk later. In this system IgE-allergen interaction can apparently result in both the immediate and late pulmonary responses. The presence of IgG results in blunting rather than in enhancing of the responsiveness, and the response can be seen in the absence of cellular immune mechanisms.