Ciclesonide modulates in vitro allergen-driven activation of blood mononuclear cells and allergen-specific T-cell blasts

BackgroundCiclesonide, an inhaled corticosteroid with almost no affinity for the glucocorticoid receptor, is highly effective in downregulating in vitro pro-inflammatory activities of airway parenchymal cells when converted into the active metabolite desisobutyryl-ciclesonide.ObjectiveWe evaluate whether ciclesonide could effectively downregulate also antigen- or allergen-induced activation of peripheral blood mononuclear cell and of allergen-specific T-cell blasts.MethodsPeripheral blood mononuclear cells were isolated from non atopic and atopic asthmatic children sensitized to Phleum pratense (PhlP5). Proliferation toward Candida albicans or PhlP5 in the presence of ciclesonide or desisobutyryl-ciclesonide (0.003–3.0 μM) was evaluated as [3H]thymidine incorporation. Modulation of PhlP5-specific T-cell blasts proliferation and PhlP5-induced interleukin 4 expression by ciclesonide and desisobutyryl-ciclesonide were measured.ResultsPeripheral blood mononuclear cell proliferation to C. albicans was dose-dependently inhibited by 0.3–3.0 μM ciclesonide and desisobutyryl-ciclesonide but inhibition by desisobutyryl-ciclesonide was higher. A significant proliferation to PhlP5 was observed only in cultures from atopic subjects: an effective downregulation was already detected at 0.03 μM ciclesonide and 0.003 μM desisobutyryl-ciclesonide (complete inhibition at 3 μM ciclesonide and 0.03 μM desisobutyryl-ciclesonide). 3 μM ciclesonide and desisobutyryl-ciclesonide reduced the PhlP5-specific T-cell blast proliferation and interleukin 4-producing cell proportion.Conclusions and clinical relevanceThese in vitro data, obtained at concentrations similar to those reached in vivo at bronchial level, are in favor of an efficient inhibition of ciclesonide on the T-cell mediated response toward allergens. Additional studies are required to confirm these preliminary data on the reduced activity of the drug on allergen-specific T-cell blast activation that may have clinical relevance.

► Ciclesonide (CIC) is converted in the airways into its active form known to have a remarkable anti-inflammatory activity.
► We study the effect of CIC on mononuclear cells/allergen-specific T-cell blast activation.
► At doses similar to those obtained in vivo at bronchial level, CIC was more effective in reducing PBMC proliferation to the allergen than to the antigen and showed a reduced activity on allergen-specific T-cell blast activation.
► Additional studies are needed to confirm the reduced activity of CIC on allergen-specific T-cell blast activation that may have clinical relevance.