Eosinophil locomotion and the release of IL‐3 and IL‐5 by allergen‐stimulated mononuclear cells are effectively downregulated in vitro by budesonide

Abstract

Treatment of allergic asthma with inhaled corticosteroids, such as budesonide (BDN), results in downregulation of T-cell activation and of eosinophil recruitment. Since blood concentrations of BDN, although significantly lower than those measured in the lung, may still have anti-inflammatory effects, we evaluated the activity of BDN in vitro on: allergen-induced release of lymphokines involved in eosinophil chemotaxis (i.e. IL-3 and IL-5), at drug concentrations similar to those obtained in vivo in the lung (10-8 M), and eosinophil locomotion, at "systemic concentrations' of the drug (10(-10)M and 10(-9)M). Twenty-three atopic asthmatic subjects (atopics) sensitized to Dermatophagoides pteronyssinus (Dp) and seven non-atopic healthy subjects (controls) were studied. Purified blood mononuclear cells (BMC) were stimulated with Dp, with or without BDN 10(-8) M and, after 6 days, the supernatants were collected and frozen to test their chemotactic activity toward purified blood eosinophils and their levels of interleukin (IL)-3 and IL-5 by immunoassay. BMC were then pulsed for additional 18 h with [3H]thymidine to evaluate allergen-induced T-cell proliferation. In addition, to test possible direct effects of 'systemic concentrations' of the drug on eosinophil locomotion, blood eosinophils were incubated for 1 h with BDN (10(-10) M and 10(-9) M) prior to test their chemotactic response toward recombinant human IL-3 and IL-5. Stimulation of BMC from atopics with Dp induced a statistically significant increase in [3H]thymidine incorporation (P < 0.05); secretion of chemotactic factors for eosinophils (P < 0.001) and the release of IL-3 and IL-5 (P < 0.005 and P < 0.05 respectively). BDN, at the concentration of 10(-8) M, was able to significantly down-regulate T-cell proliferation (P < 0.05), the secretion of chemotactic factors for eosinophils (P < 0.001) and the release of IL-3 and IL-5 (P < 0.01 and P < 0.05 respectively). Similarly, "systemic concentrations' of BDN (10(-10) M and 10(-9) M) totally inhibited the chemotactic response of blood eosinophils toward recombinant human IL-3 and IL-5 (P < 0.005). Concentrations of BDN similar to those obtained in vivo are effective in inhibiting both the release of eosinophils chemotaxins by allergen-activated mononuclear cells and eosinophil locomotion.