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


OBJECTIVE
We evaluate whether ciclesonide could effectively downregulate also antigen- or allergen-induced activation of peripheral blood mononuclear cell and of allergen-specific T-cell blasts.


METHODS
Peripheral 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 [(3)H]thymidine incorporation. Modulation of PhlP5-specific T-cell blasts proliferation and PhlP5-induced interleukin 4 expression by ciclesonide and desisobutyryl-ciclesonide were measured.


RESULTS
Peripheral 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
These 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.
Pediatric Pulmonary and Allergy Unit, G. Gaslini Institute, Largo G. Gaslini 5, 16147 Genoa, Italy. michelasilvestri@ospedale-gaslini.ge.it
Michela
M
Silvestri
Fabio
F
Morandi
Vito
V
Pistoia
Ignazia
I
Prigione
Giovanni A
GA
Rossi
D000485:Allergens / Q000276:immunology / Q000378:metabolism; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D052179:Antigens, Plant / Q000276:immunology / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D005260:Female; D005656:Fungal Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007114:Immunization; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D031784:Phleum / Q000276:immunology; D011282:Pregnenediones / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
D000485:Allergens; D018926:Anti-Allergic Agents; D052179:Antigens, Plant; D005656:Fungal Proteins; D011282:Pregnenediones; D015847:Interleukin-4; C120481:ciclesonide