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.
CONCLUSION: 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.