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Inhibition by the immunosuppressive agent FK‐506 of antigen‐induced airways eosinophilia and bronchial hyperreactivity in mice
Author(s) -
Eum SeokYong,
ZuanyAmorium Claudia,
Lefort Jean,
Pretolani Marina,
Vargaftig B Boris
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0700860
Subject(s) - bronchoconstriction , eosinophil , methacholine , eosinophilia , immunology , ovalbumin , bronchoalveolar lavage , bronchial hyperresponsiveness , medicine , antigen , immunoglobulin e , asthma , lung , respiratory disease , antibody
The effect of the immunosuppressive agent, FK‐506, on allergen‐induced airways eosinophilia and bronchial hyperreactivity (BHR) in hyper IgE mice (BP2 selection) was investigated. Administration of FK‐506 at 2 mg kg −1 s.c., 1 h before and 5 h after the first of four ovalbumin challenges, reduced the recruitment of eosinophils into the bronchoalveolar lavage fluid (BALF) from 1.36±0.22×10 5 to 0.53±0.24×10 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. The antigen‐induced interleukin (IL)‐5 formation in the BALF and serum was inhibited by FK‐506 by 75% in both instances. FK‐506 failed to modify the bronchoconstriction in BP2 mice, suggesting that different mechanisms are involved in acute bronchoconstriction and BHR. The increased number of CD4+, CD8+, CD3+ T lymphocytes in the BALF of antigen‐challenged mice was unaffected by FK‐506. 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.British Journal of Pharmacology (1997) 120 , 130–136; doi: 10.1038/sj.bjp.0700860