Inhibition by the immunosuppressive agent FK-506 of antigen-induced airways eosinophilia and bronchial hyperreactivity in mice.
1. The effect of the immunosuppressive agent, FK-506, an allergen-induced airways eosinophilia and bronchial hyperreactivity (BHR) in hyper IgE mice (BP2 selection) was investigated. 2. Administration of FK-506 at 2 mg kg-1 s.c., 1 h before and 5 h after the first four ovalbumin challenges, reduced the recruitment of eosinophils into the bronchoalveolar lavage fluid (BALF) from 1.36 +/- 0.22 x 10(5) to 0.53 +/- 0.24 x 10(5) cells ml-1 (n = 5-6, P < 0.05; 60% inhibition), inhibited by 80% BHR in response to i.v. 5-HT and practically suppressed BHR in response to inhaled methacholine. 3. The antigen-induced interleukin (IL)-5 formation in the BALF and serum was inhibited by FK-506 by 75% in both instances. 4. FK-506 failed to modify the bronchoconstriction in BP2 mice, suggesting that different mechanisms are involved in acute bronchoconstriction and BHR. 5. The increased number of CD4+, CD8+, CD3+ T lymphocytes in the BALF to antigen-challenged mice was unaffected by FK-506. 6. These findings indicate that antigen-induced in vivo IL-5 release and eosinophil, but not T-cell, infiltration into the bronchial lumen of sensitized BP2 mice are targets for the anti-allergic activities of FK-506.
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Unité de Pharmacologie Cellulaire, Institut Pasteur 25, France.
Zuany-Amorim
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Lefort
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Pretolani
M
M
Vargaftig
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BB
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004802:Eosinophilia / Q000503:physiopathology*; D019084:Fluorescent Antibody Technique, Indirect; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology; D012129:Respiratory Function Tests; D013601:T-Lymphocytes / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D015848:Interleukin-5; D010047:Ovalbumin; D016559:Tacrolimus