Evaluation of the inhibitory effects of budesonide on the mitogen-induced or the allergen-induced activation of blood mononuclear cells isolated from asthmatic patients.
BACKGROUND
Corticosteroids are thought to be effective in the treatment of allergic reactions including bronchial asthma because they not only have anti-inflammatory effects, but also downregulate the processes of T-cell activation.


OBJECTIVE
To evaluate in vitro the inhibitory activity of budesonide, a widely used inhaled corticosteroid, on allergen-induced mononuclear cell activation.


METHODS
Thirty-one atopic asthmatic patients, sensitized to Dermatophagoides pteronyssinus (Der p) were studied. Peripheral blood mononuclear cells isolated from these patients were used to determine the ability of budesonide to inhibit (1) the proliferative response of blood T-lymphocytes to Der p allergen extract and to phytohemoagglutinin (PHA) and (2) the release of different cytokines known to modulate the interaction between T-lymphocytes and monocytes in the allergic processes.


RESULTS
A significant T-cell proliferation was observed both in the presence of PHA (P < .001) and that of Der p allergen extract (P < .05), and was associated with increased release of interleukin-2 [IL-2 (respectively P < .001 and P < .01)], gamma-interferon [gamma-IFN (respectively P < .001 and P < .01)], granulocyte-macrophage colony-stimulating factor [GM-CSF (respectively P < .01 and P < .001)], interleukin-1 beta [IL-1 beta (respectively P < .05 and P < .01)], and tumor necrosis factor-alpha [TNF-alpha (P < .05 each comparison)]. The addition at the beginning of the cell cultures of different concentrations (from 10(-10) M to 10(-7) M) of budesonide, and as control of dexamethasone, induced a dose-dependent inhibition of T-cell proliferation, in response to PHA and Der p. Budesonide at the lowest concentrations tested (10(-10) M and 10(-9) M) was more effective than dexamethasone. Budesonide was also more active than dexamethasone in inhibiting the release of IL-2, gamma-IFN, IL-1 beta and GM-CSF (in both PHA-stimulated and Der p-stimulated blood mononuclear cell cultures) and TNF-alpha (in Der p-stimulated blood mononuclear cell cultures).


CONCLUSIONS
Budesonide is equally or more effective than dexamethasone in inhibiting the allergen-induced T-cell proliferation and in reducing the release of cytokines by allergen-stimulated blood mononuclear cells.
Oddera
S
S
Division of Pneumology, G. Gaslini Institute, Genoa, Italy.
Silvestri
M
M
Sacco
O
O
Lantero
S
S
Morelli
M C
MC
Rossi
G A
GA
D000328:Adult; D000485:Allergens / Q000494:pharmacology; D001249:Asthma / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019819:Budesonide; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D011282:Pregnenediones / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D000485:Allergens; D001993:Bronchodilator Agents; D003470:Culture Media; D016207:Cytokines; D008934:Mitogens; D011282:Pregnenediones; D019819:Budesonide