The role of interleukin-5 (IL-5) in allergic airway hyperresponsiveness in mice.
In order to investigate the role of IL-5 in allergic airway inflammation and hyperresponsiveness, the effects of rat anti-IL-5 monoclonal antibody (NC-17), recombinant soluble murine IL-5 receptor, and some immunosuppressors were studied in mice model. Three inhalations of an antigen by actively sensitized animals resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (mononuclear cells and eosinophils) and the amount of IL-4 and IL-5 in bronchoalveolar lavage fluid (BALF) increased significantly. NC-17 and soluble IL-5 receptor inhibited the antigen-induced increase of eosinophils with little effect on bronchial hyperreactivity. Cyclosporin A, FK-506, and cyclophosphamide clearly inhibited the antigen-induced increase of IL-5 and eosinophils in BALF. Airway hyperreactivity is inhibited by cyclosporine A and FK-506 but not by cyclophosphamide. Furthermore, to investigate the role of mast cells in the onset of allergic airway hyperreactivity, we have examined the effect of repeated antigen provocation in WBB6F1-W/Wv mice (W/Wv), mast-cell-deficient mice. Whereas significant elevation of IL-5 level and the number of eosinophils on BALF was observed, airway reactivity to acetylcholine was not changed at all. These results indicate that IL-5 may play an important role for the antigen-induced eosinophilia in BALF but not in airway hyperresponsiveness in mice.
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
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Nagai
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Yamaguchi
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Tanaka
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D003520:Cyclophosphamide / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019081:O Antigens / Q000494:pharmacology; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology
D015848:Interleukin-5; D019081:O Antigens; D015847:Interleukin-4; D003520:Cyclophosphamide; D000109:Acetylcholine; D016559:Tacrolimus