Effects of "systemic" budesonide concentrations on in vitro allergen-induced activation of blood mononuclear cells isolated from asthmatic patients

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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)