Role of mast cells, eosinophils and IL-5 in the development of airway hyperresponsiveness in sensitized mice

Authors


H. Nagai, Department of Pharmacology, Gifu Pharmaceutical University, 5–6–1 Mitahora-higashi, Gifu 502, Japan.

Summary

Background and objective In order to study the role of mast cells and IL-5 in allergen-induced airway hyperreactivity in mice, airway responsiveness in WBB6F1-W/Wv mice (mast cell deficient) and the effects of anti-IL-5 monoclonal antibody (NC-17) and three anti-allergic drugs (N-556, ketotifen and amlexanox) on airway hyperreactivity in Balbc mice were studied.

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 acetyleholine was measured and broncho-alveolar lavage fluid (BALF) was obtained.

Resutls Three inhalations of OA caused an increase in leucocytes (including eosinophils). accompanied by increases in IL-5 in BALF, and airway hyperreaetivity to acetylcholine in Balb/c and WBB6F1- +/+ mice. In WBB6F1-W/Wv mice, antigen inhalation resulted in increases in leucocytes and IL-5 in BALF but did not result in airway hyperreactivity. NC-17 at doses between 10 and 20μg (intratracheal injection) inhibited the antigen-induced eosinophilia but did not affect airway hyperreaetivity in Balb/c mice. Three ‘anti-allergie’ drugs clearly inhibited antigen-induced increases in IL-5 levels and the number of eosinophils in BALF, but did not alTect airway hyperreactivity in Balb/c mice.

Conclusions These data suggest that mast cells play an important role in the onset of airway hyperreactivity but do not play a role in the production of IL-5 and eosinophilia. Furthermore., indicate that the inhibition of IL-5 is not always associated with a reduetion in antigen-induced airway hyperreactivity in mice.

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