IgE and eosinophil regulation in a murine model of allergic aspergillosis.
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.
Department of Medicine, Medical College of Wisconsin, Milwaukee.
V P
VP
Kurup
H
H
Choi
P S
PS
Murali
R L
RL
Coffman
D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000946:Antigens, Fungal / Q000008:administration & dosage / Q000276:immunology; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000097:blood / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D004802:Eosinophilia / Q000097:blood / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000502:physiology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D007074:Immunoglobulin G; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma