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Eosinophils are recruited to the airways during allergic reactions, but animal models have shown that their mere presence is not sufficient for the development of bronchopulmonary hyperreactivity. Other factors, such as immunoglobulin (Ig)E, seem to be required. Using mice selected for the production of large amounts of IgE, the effects of antibody neutralization of IgE on antigen-induced lung recruitment of eosinophils and induction of bronchopulmonary hyperreactivity and of other indicators of inflammation were studied. A monoclonal non-anaphylactogenic rat anti-mouse IgE (mAb1-5), given within 24 h of the challenge with antigen, reduced tissue eosinophilia, the recruitment of IgE-bearing cells identified as basophils, mucous cell metaplasia, anaphylactic bronchoconstriction and bronchopulmonary hyperreactivity. mAb1-5 inhibited interleukin (IL)4 titres in the bronchoalveolar lavage fluid, but not those of I1-5. Inhibition by mAb1-5 may result from competitive displacement of immunoglobulin E from its different receptors, thus preventing cell stimulation. Moreover, the inhibition of the massive recruitment of immunoglobulin E-bearing basophils into the lungs within hours after challenge and of interleukin4 production by mAb1-5 may be important factors leading to the reduction of pulmonary eosinophilia and bronchopulmonary hyperreactivity. Thus, immunoglobulin (Ig)E and allergic IgE-bearing cells seem to play an essential role in the initial development of the late allergic airway responses.

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.

Background: Infiltration of inflammatory cells in the airways is a constant characteristic of asthma and is considered to result in bronchial hyperreactivity (BHR). We have recently developed a model of BHR using a selection of mice, named BP2, which display eosinophil-dependent BHR following antigen challenges. An anti-IL-5 antibody suppressed antigen-induced eosinophil recruitment to the airways and BHR in BP2 mice., Objective: To investigate the implication of infiltrated inflammatory cells in the induction of BHR in mice., Methods: The effects of glucocorticosteroid dexamethasone on airways eosinophilia and BHR were observed., Results: Administration of dexamethasone at the dose of 1.25 mg/kg i.p. 1 h before each of four antigen provocations suppressed the airways eosinophilia and BHR in response to intravenous 5-HT and to aerosolized methacholine, as well as IL-5 production in the BALF and in the serum. By contrast, dexamethasone failed to reduce anaphylactic bronchoconstriction., Conclusions: These results suggest that dexamethasone exerts its inhibitory effects on antigen-induced airways eosinophilia in mice by inhibiting IL-5 production, but that it does not block the liberation of anaphylactic mediators in mice.