EOSINOPHIL LOCOMOTION AND THE RELEASE OF IL-3 AND IL-5 BY ALLERGEN-STIMULATED MONONUCLEAR-CELLS ARE EFFECTIVELY DOWN-REGULATED IN-VITRO BY BUDESONIDE

Background Treatment of allergic asthma with inhaled corticosteroids, such as budesonide (BDN), results in downregulation of T-cell activati on 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 o f BDN in vitro on: allergen-induced release of lymphokines involved in eosinophil chemotaxis (i.e. IL-3 and IL-5), at drug concentrations si milar 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) sens itized to Dermatophagoides pteronyssinus (Dp) and seven non-atopic hea lthy subjects (controls) were studied. Purified blood mononuclear cell s (BMC) were stimulated with Dp: with or without BDN 10(-8) M and, aft er 6 days, the supernatants were collected and frozen to test their ch emotactic activity toward purified blood eosinophils and their levels of interleukin (IL)-3 and IL-5 by immunoassay. BMC were then pulsed fo r additional 18 h with [H-3]thymidine to evaluate allergen-induced T-c ell proliferation. In addition, to test possible direct effects of sys temic concentrations' of the drug on eosinophil locomotion, blood eosi nophils 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 statis tically significant increase in [H-3]thymidine incorporation (P < 0.05 ); secretion of chemotactic factors for eosinophils (P < 0.001) and th e 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-regu late T-cell proliferation (P < 0.05), the secretion of chemotactic fac tors 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 res ponse 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 chem otaxins by allergen activated mononuclear cells and eosinophil locomot ion.