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Eosinophil locomotion and the release of IL‐3 and IL‐5 by allergen‐stimulated mononuclear cells are effectively downregulatedin vitroby budesonide

机译:Eosinophil locomotion and the release of IL‐3 and IL‐5 by allergen‐stimulated mononuclear cells are effectively downregulatedin vitroby budesonide

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SummaryBackgroundTreatment of aliergic asthma with inhaled corticosteroids, such as budesonide (BDN), results in downregulation of T‐cell activation and of eosinophil recruitment.ObjectiveSince blood concentrations of BDN, although significantly lower than those measured in the lung, may still have anti‐inflammatory effects, we evaluated the activity of BDNin vitroon: allergen‐induced release of lymphokines involved in eosinophil chemotaxis (i.e. IL‐3 and IL‐5), at drug concentrations similar to those obtainedin vivoin the lung (10−8M), and eosinophil locomotion, at ‘systemic concentrations’ of the drug (10−10M and 10−9M).MethodsTwenty‐three atopic asthmatic subjects (atopics) sensitized toDermatophagoides pteronyssinus(Dp) and seven non‐atopic healthy subjects (controls) were studied. Purified blood mononuclear cells (BMC) were stimulated with Dp, with or without BDN 10−8M and, after 6 days, the supernatants were collected and frozen to test their ehemotactie activity toward purified blood eosinophils and their levels of interleukin (IL)‐3 and IL‐5 by immunoassay. BMC were then pulsed for additional 18h with 3Hthymidine 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 (10−10M and 10−9M) prior to test their ehemotactie response toward recombinant human IL‐3 and IL‐5.ResultsStimulation of BMC from atopies with Dp induced a statistically significant increase in Hthymidine incorporation (P<0.05); secretion of ehemotactie factors for eosinophils (P<0.001) and the release of IL‐3 and IL‐5 (P<0.005 andP<0.05 respectively). BDN, at the concentration of 10−8M, was able to significantly down‐regulate T‐cell proliferation (P<0.05), the secretion of ehemotactie factors for eosinophils (P<0.001) and the release of IL‐3 and IL‐5 (P<0.01 andP<0.05 respectively). Similarly, “systemic concentrations” of BDN (10−10M and 10−9M) totally inhibited the ehemotactie response of blood eosinophils toward recombinant human IL‐3 and IL‐5 (P<0.005).ConclusionsConcentrations of BDN similar to those obtainedin vivoare effective in inhibiting both the release of eosinophils chemot

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