Inhibition of allergic airways inflammation and airway hyperresponsiveness in mice by dexamethasone: Role of eosinophils, IL-5, eotaxin, and IL-13

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:111

Article

Eum, SY ; Maghni, K ; Hamid, G ; Eidelman, DH ; Campbell, H ; Isogai, S ; Martin, JG

关键词: asthma;    glucocorticoid;    eotaxin;    IL-5;    murine model;   

DOI  :  10.1067/mai.2003.1416

来源: Elsevier

【 摘 要 】

Background: Glucocorticoids inhibit allergen-induced airway eosinophilia and airway hyperresponsiveness (AHR). Whether gIucocorticoids mediate their effects on AHR by inhibiting eotaxin and IL-5, 2 of the principal mediators of eosinophilia, or through IL-13, an important mediator of AHR, has not been established. Objective: We sought to investigate the effects of glucocorticoids on airway eosinophilia and the expression of IL-5, eotaxin, and IL-13 in relation to the induction of AHR in a murine model of allergic asthma. Methods: Dexamethasone (4 mg/kg) and mAbs against eotaxin (80 mug/kg) and IL-5 (100 mug/kg) singly and in combination were administered to immunized mice before antigen challenge. Airway responsiveness to methacholine was measured in anesthetized and mechanically ventilated animals. Eotaxin, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), lung homogenates, or both were measured by means of ELISA. Results: A single antigen challenge induced AHR that lasted at least 10 days. Eotaxin protein and mRNA levels increased in lung tissue but not in BALF after challenge. IL-5 protein and mRNA levels increased both in BALF and in lung tissue. Dexamethasone reduced airway eosinophilia, AHR, and protein and mRNA for eotaxin and IL-5. Anti-murine eotaxin and anti-IL-5 antibodies alone and in combination reduced the ovalbumin-induced airway eosinophilia significantly but failed to inhibit AHR. Both dexamethasone and anti-IL-5/anti-eotaxin inhibited the increases in lung IL-13 levels after ovalbumin challenge to a similar extent. Conclusion: These findings suggest that the inhibition of AHR by the glueocorticoid dexamethasone does not appear to be explained by effects on eosinophilia, eotaxin, IL-5, or IL-13.

【 授权许可】

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