Effects of "systemic" budesonide concentrations on in vitro allergen-induced activation of blood mononuclear cells isolated from asthmatic patients.
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)
Oddera
S
S
Division of Pneumology, G. Gaslini Institute, Genoa, Italy.
Silvestri
M
M
Sacco
O
O
Lantero
S
S
Morelli
M C
MC
Rossi
G A
GA
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
D000485:Allergens; D039741:Antigens, Dermatophagoides; D016207:Cytokines; D005938:Glucocorticoids; D006023:Glycoproteins; D006684:HLA-DR Antigens; D011282:Pregnenediones; D015375:Receptors, Interleukin-2; D019819:Budesonide