Acute hypersensitivity pneumonitis in the rabbit. I. An animal model with horseradish peroxidase as antigen.

An experimental model of acute hypersensitivity pneumonitis was developed in rabbits using horseradish peroxidase as antigen. The lesion, produced by aerosol challenge with horseradish peroxidase 21 days after a single parenteral immunization with horseradish peroxidase and complete Freund adjuvant, was characterized by diffuse infiltration of respiratory bronchioles and of alveolar ducts and walls with approxomately equal numbers of mononuclear cells (lymphocytes and macrophages) and polymorphonuclear cells. This lesion, which was specific for the antigen, was distinct from the variable granulomatous component that was directly attributable to the use of complete Freund adjubant. Development of the lesion did not correlate with the humoral immune response, as indicated by antigen-binding, precipitin, and homologous passive cutaneous anaphylaxis assays, by negative serum transfer studies, by lack of correlation with immediate and intermediate Arthuslike) skin reactivity, by absence of electron microscopic and immunofluorescent evidence for immune complex processes, and by lack of evidence for complement activation. Development of the lesion did correlate with delayed (12- to 48-hour) skin reactivity, although rigid identification of cell-mediated immunity was not possible on histologic examination.