Inhibitory effect of budesonide alone and in combination with formoterol on IL-5 and RANTES production from mononuclear cells.
BACKGROUND
The use of a budesonide (BUD)/formoterol (FOR) combination (Symbicort) for both maintenance and reliever therapy reduces the exacerbation of asthma better than the traditional fixed-dose regimens. In the early stage of exacerbation, the combination therapy could intervene with the development of subsequent airway inflammation. The objective of the study was to evaluate whether in the early stage of cell activation the use of BUD/FOR combination would modify the adhesion of eosinophils or production of cytokines from mononuclear cells.


METHODS
Human peripheral blood eosinophils, pretreated with BUD (0.1 microM), FOR (0.1 microM) or BUD/FOR combination for 30 min at 37 degrees C, were stimulated with IL-5, leukotriene D4 or phorbol myristate acetate, and eosinophil adhesion was evaluated using an eosinophil peroxidase assay. BUD (0.1 microM), FOR (0.1 microM) or BUD/FOR combination was added to the peripheral blood mononuclear cells stimulated with ionomycin plus phorbol myristate acetate. Concentrations of IL-5 and RANTES in the cell supernatant were measured using ELISA.


RESULTS
BUD, FOR or BUD/FOR combination did not modify the eosinophil adhesion induced by any stimulators. In contrast, BUD or BUD/FOR combination significantly reduced the productions of IL-5 and RANTES in peripheral blood mononuclear cells (BUD: p < 0.0001, p = 0.027 vs. control; BUD/FOR: p < 0.0001, p = 0.031 vs. control) when the drugs were added 15 min, but not 4 h, following cell stimulation.


CONCLUSIONS
In the early stage of exacerbation of asthma, inhaled BUD may suppress the progression of the allergic inflammatory cascade by inhibiting the mononuclear cells. These results also underline the importance of using BUD in rescue inhaler.
Soma
Tomoyuki
T
Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
Takaku
Yotaro
Y
Kobayashi
Takehito
T
Hagiwara
Koichi
K
Kanazawa
Minoru
M
Uematsu
Kazutsugu
K
Nagata
Makoto
M
D000328:Adult; D001993:Bronchodilator Agents / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D018946:Chemokine CCL5 / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008297:Male
D001993:Bronchodilator Agents; D018946:Chemokine CCL5; D016207:Cytokines; D004983:Ethanolamines; D015848:Interleukin-5; D019819:Budesonide; D000068759:Formoterol Fumarate