The effect of anti-IL-4 monoclonal antibody, rapamycin and interferon-gamma on airway hyperreactivity to acetylcholine in mice.
BACKGROUND
The role of IgE in airway hyperreactivity is obscure.


OBJECTIVE
In order to clarify the role of IgE in airway hyperreactivity, we investigated the effect of anti-IL-4 monoclonal antibody, rapamycin and interferon-gamma on the antigen-induced IgE response, airway eosinophilia and hyperreactivity in mice.


METHODS
Mice were immunized with an antigen (ovalbumin; OA) at intervals of 12 days. OA was inhaled 10 days after the secondary immunization. Twenty-four hours after the last inhalation, airway reactivity to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was obtained.


RESULTS
Three inhalations of antigen caused an increase in the number of eosinophils in bronchoalveolar lavage fluid (BALF) and in airway hyperreactivity to acetylcholine with a significant elevation of serum IgE level. Anti-IL-4 at a dose of 1000 micrograms/animal and rapamycin at doses between 0.1 and 1 mg/kg inhibited the IgE production, but did not affect the airway eosinophilia or hyperreactivity to acetylcholine. In contrast, IFN-gamma clearly inhibited the antigen-induced airway eosinophilia and hyperreactivity, but did not affect the IgE antibody production.


CONCLUSIONS
These results suggest that the inhibition of IgE production does not suppress the onset of airway hyperreactivity and eosinophilia in mice, and that IFN-gamma inhibits the antigen-induced airway hyperreactivity, probably due to the inhibition of airway eosinophilia.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Maeda
Y
Y
Tanaka
H
H
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000209:etiology / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D015847:Interleukin-4 / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011090:Polyenes / Q000494:pharmacology*; D020123:Sirolimus
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011090:Polyenes; D015847:Interleukin-4; D007073:Immunoglobulin E; D000109:Acetylcholine; D020123:Sirolimus