IgE and eosinophil regulation in a murine model of allergic aspergillosis

Abstract

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.

Second‐Hand Smoke Increases Bronchial Hyperreactivity and Eosinophilia in a Murine Model of Allergic Aspergillosis

“…IL5, known to increase eosinophilic leukocytes (Galli et al, 1991;Kurup et al, 1994b;Hogaboam et al, 1999) was detected from anti-CD3 stimulated cells. However, additional sources of IL5 from smoke stimulated mast cells were not measured in vitro, which may explain the lack of enhancement of IL5, after in vitro stimulation of lung cells from the Af þ ETS group when compared to the Af þ AIR group.…”

“…ABPA is prevalent among patients with cystic fibrosis (Laufer et al, 1984) and is characterized by elevated levels of serum IgE and eosinophils indicating a Th2 response (Kauffman et al, 1995). Indeed, in a murine model of ABPA, Th2 cytokines, particularly IL4 and IL5, were detected in cell cultures from the lungs (Kurup et al, 1992;Kurup et al, 1994a) and BAL (Grunig et al, 1997) of Af sensitized mice and administration of antibodies to IL4 and IL5 abrogated the IgE and eosinophilia in these animals (Kurup et al, 1994b).…”

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

“…In contrast to OVA, immunity to type II allergens derived from A. fumigatus is distinctly allergic, dominated by the presence of lung parenchymal and airway eosinophils and Th cells type 2 (Th2 cells), 4 elevated serum titers of IgE, and the physiologic sequelae of this inflammation including airway hyperresponsiveness and airway mucus overproduction (13,14,(21)(22)(23). T and/or B cell tolerance is not observed and robust inflammation is induced without the need for extrapulmonary Ag challenge or additional adjuvants.…”

Interleukin-5-mediated Allergic Airway Inflammation Inhibits the Human Surfactant Protein C Promoter in Transgenic Mice

“…Most experimental allergen challenges were conducted utilizing A. fumigatus as an antigen. It should be noted that this antigen was selected because it represents a model antigen that has already been extensively analyzed (33)(34)(35). To prove that the results were not strictly related to this allergen, an unrelated antigen (OVA) was used to demonstrate that the effect was not allergen-specific.…”