Background. Treatment of allergic asthma with inhaled corticosteroids, such as budesonide (BDN), results in downregulation of T-cell activation and of eosinophil recruitment. Objective. 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). Methods. 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. Results. 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 downregulate 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). Conclusions. 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.
|Number of pages||9|
|Journal||Clinical and Experimental Allergy|
|Publication status||Published - 1996|
- T cells
ASJC Scopus subject areas