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  • 11
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Blood levels of inhaled corticosteroids are significantly lower than those measured in the lung, but their concentration could still have anti-inflammatory effects. To determine whether budesonide, at concentrations similar to those obtained in blood after drug inhalation (10 −9 M), could downregulate the allergen-induced activation of mononuclear cells, we studied 21 atopic patients, sensitized to Dermatophagoides pteronyssinus (Der p). On blood mononuclear cells, isolated from these patients, incubated with Der p allergen extract and with or without budesonide, we evaluated: 1) the proliferative response of T cells; 2) the expression of two surface activation markers, the HLA-DR antigens and the interleukin (IL)-2 receptors; and 3) the release of cytokines known to modulate the allergic processes. Allergen-induced T-cell proliferation was associated with increased HLA-DR antigen and IL-2 receptor expression (P 〈 0.001), and with increased release of IL-2, interferon-gamma (IFN-γ), IL-1β, tumor necrosis factor-alpha (TNF-α), and granulocyte/macrophage colony-stimulating factor (GM-CSF). The addition of budesonide at the beginning of the cell cultures induced a dose-dependent inhibition of T-cell proliferation, still significant (P 〈 0.05) at the lowest concentrations tested (10 −9 and 10−10 M). A significant inhibitory effect on T-cell proliferation was also present when budesonide (10 −9 M) was added to the cell cultures 3 or 5 days after the beginning of the cell cultures. In addition, budesonide 10−9 M significantly decreased the expression of IL-2 receptors (P 〈 0.05), but not of HLA-DR antigens, and significantly reduced the release of IL-1β and GM-CSF (JP 〈 0.05), but not of IL-2, IFN-γ, and TNF-α. Thus, the blood concentrations of budesonide, after drug inhalation, may exert some anti-inflammatory effect, downregulating both “local” (through the bronchial circulation) and “systemic” allergen-specific immune reactions.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-1750
    Keywords: Key words: Eosinophils—Asthma—Atopy—Bronchial hyperresponsiveness—Methacholine—Bronchoalveolar lavage—Bronchial lavage—Inflammation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. To characterize the cellular inflammation at the bronchial and bronchoalveolar levels, we evaluated 43 patients with asthma who were sensitized to house dust mites. On 2 consecutive days patients underwent methacholine challenge and allergen bronchial challenge. In addition, 6, 24, or 72 h after allergen challenge, fiberoptic bronchoscopy with bronchial lavage (BL) and bronchoalveolar lavage (BAL) was performed. Patients belonging to the 6-h, 24-h, or 72-h group were divided further into two subgroups: those with isolated early response to allergen (LAR−), and those with dual response to allergen (LAR+). The percentage of eosinophils and of epithelial cells in BAL fluid was significantly higher in LAR+ than in LAR− patients in the 6-h group (p 〈 0.05, each comparison), but not 24 or 72 h after (p 〉 0.05, each comparison). Similarly, the proportion of BL eosinophils was also higher in LAR+ than in LAR− patients, both in the 6-h and in the 24-h group (p 〈 0.05, each comparison). In addition, increased proportions of BL neutrophils were present in the LAR+ patients belonging to the 24-h group (p 〈 0.05). Comparing ``proximal'' = BL vs ``distal'' = BAL data, we found a significantly higher proportion of epithelial cells in BL compared with BAL, in both LAR− and LAR+ subjects, either 6, or 24, or 72 h after challenge (p 〈 0.01, each comparison) and increased percentages of BL neutrophils and eosinophils in LAR+ patients (p 〈 0.05, each comparison), but not in LAR− patients, in the 24-h group. The percentages of BL or BAL macrophages and lymphocytes did not differ significantly among the different patient groups. These data indicate that the development of LAR after allergen inhalation challenge is associated with an early recruitment of eosinophils and with epithelial desquamation in the airways. In addition, after allergen challenge epithelial desquamation is more pronounced in the proximal than in the distal airways, independently of the type of bronchial response.
    Type of Medium: Electronic Resource
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