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Exposure of BALB/c mice to Aspergillus fumigatus (Af), the antigen responsible for causing allergic bronchopulmonary aspergillosis in humans, caused elevated levels of serum immunoglobulin E (IgE) and peripheral blood and lung eosinophilia similar to that observed in the human disease. We have investigated the role of interleukin-4 (IL-4), IL-5 and interferon-gamma in regulating IgE and eosinophilia in the mouse model. Animals were immunized by intraperitoneal injections of soluble Af antigens adsorbed to alum. These animals developed elevated IgE and Af specific IgG1 and were then treated with anticytokine monoclonal antibodies before the final exposure to particulate Af antigens by the intranasal route. The results showed that anti-IL-5 abrogated eosinophilia in mice, while those treated with anti-IL-4 retained the same or reduced IgE levels compared to pretreatment levels. All anti-IL-5, anti-IFN-gamma, and control antibody-treated animals showed enhanced IgE levels. Anti-IFN-gamma treatment of mice resulted in marked enhancement of eosinophilia compared to all other groups. Eosinophil numbers observed in the histological sections of the lungs confirmed the eosinophilia detected in the peripheral blood. These results indicate that the increase in IgE and eosinophils after exposure to Af antigens in BALB/c mice are due to Af-induced production of IL-4 and IL-5 and that both IgE and eosinophilia are independently regulated.

The effect of multiple divided doses compared with single-dose injections of antibodies to murine interleukin (IL)-4 and IL-5 in their respective downregulation of IgE and eosinophilia developing in a model of allergic aspergillosis is investigated. BALB/c mice were exposed to Aspergillus fumigatus antigens (Af) before and along with anticytokine antibodies. The kinetics of blood eosinophils, eosinophil peroxidase (EPO) in bone-marrow cells, serum levels of IgE and Af-specific antibodies, Af-induced cytokine production and mRNA, and lung histology were studied. The results indicate that only multiple anti-IL-5 antibodies were effective in maintaining baseline levels of blood eosinophils. Multiple anti-IL-4 antibodies also downregulated eosinophils in the bone marrow, lung, and peripheral blood, although to a lesser extent than in anti-IL-5 antibody-injected mice. Significant correlation between the EPO activity and the eosinophil numbers in anticytokine antibody-treated mice was observed. The different anti-IL-4 antibody treatments downregulated IgE to the same extent. We conclude that multiple divided doses of anti-IL-5 antibodies are required to sustain normal eosinophil levels in murine allergic aspergillosis. This information may be significant in the therapy of pulmonary allergic diseases.

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