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, on 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 of four ovalbumin challenges, reduced the recruitment of eosinophils into the bronchoalveolar lavage fluid (BALF) from 1.36+/-0.22x10(5) to 0.53+/-0.24x10(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 of 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.