title: Effects of "systemic" budesonide concentrations on in vitro allergen-induced activation of blood mononuclear cells isolated from asthmatic patients.
abstract: 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-gamma), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Pneumology, G. Gaslini Institute, Genoa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Oddera
authors.forename: M
authors.initials: M
authors.lastname: Silvestri
authors.forename: O
authors.initials: O
authors.lastname: Sacco
authors.forename: S
authors.initials: S
authors.lastname: Lantero
authors.forename: M C
authors.initials: MC
authors.lastname: Morelli
authors.forename: G A
authors.initials: GA
authors.lastname: Rossi
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000097:blood* / Q000276:immunology*; D019819:Budesonide; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006023:Glycoproteins / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009994:Osmolar Concentration; D011282:Pregnenediones / Q000008:administration & dosage* / Q000627:therapeutic use; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D016207:Cytokines; D005938:Glucocorticoids; D006023:Glycoproteins; D006684:HLA-DR Antigens; D011282:Pregnenediones; D015375:Receptors, Interleukin-2; D019819:Budesonide