title: Inhibitory effect of budesonide alone and in combination with formoterol on IL-5 and RANTES production from mononuclear cells.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Soma
authors.forename: Yotaro
authors.initials: Y
authors.lastname: Takaku
authors.forename: Takehito
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Minoru
authors.initials: M
authors.lastname: Kanazawa
authors.forename: Kazutsugu
authors.initials: K
authors.lastname: Uematsu
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagata
mesh_terms: 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
chemical_list: D001993:Bronchodilator Agents; D018946:Chemokine CCL5; D016207:Cytokines; D004983:Ethanolamines; D015848:Interleukin-5; D019819:Budesonide; D000068759:Formoterol Fumarate