Biochemical interaction between effects of beclomethasone dipropionate and salbutamol or formoterol in sputum cells from mild to moderate asthmatics

Allergy. 2005 Mar;60(3):323-9. doi: 10.1111/j.1398-9995.2005.00702.x.


Background: Several in vitro studies demonstrate that corticosteroids and long-acting beta(2) agonists may have a complementary and synergistic mode of action on the inflammatory processes in asthma.

Methods: Sputum was induced in 20 mild to moderate asthmatic patients and the induced sputum cells (ISC) were cultured with beclomethasone dipropionate (BDP) 10(-7) M, salbutamol 10(-8) M and formoterol 10(-8) M either alone or in combination, BDP plus salbutamol and BDP plus formoterol, for 24 h. We measured the levels of growth macrophages-colony stimulating factor (GM-CSF), released on activation normal T cells expressed and activated (RANTES) and interleukin-8 (IL-8), in the supernatant of stimulated cells by ELISA. Furthermore, we assessed nuclear translocation of glucocorticoid receptor (GR) and the expression of beta(2) receptor in ISC by immunofluorescence and RT-PCR, respectively.

Results: The release of GM-CSF, RANTES and IL-8 in ISC was significantly reduced by BDP plus salbutamol or formoterol as compared with either drug alone (P < 0.0001). beta(2) receptor expression was increased after 30 min of incubation with BDP and continued to increase over a time period of 4 h (P < 0.0001). Furthermore after 30 min of incubation, nuclear translocation of GR was greater with BDP plus salbutamol or formoterol than with any of the drugs alone (P < 0.0001).

Conclusion: The present ex vivo study demonstrates a complementary mode of action between BDP and salbutamol or formoterol leading to an enhanced anti-inflammatory activity.

MeSH terms

  • Adult
  • Albuterol / therapeutic use*
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Beclomethasone / therapeutic use*
  • Bronchodilator Agents / therapeutic use*
  • Cells, Cultured
  • Chemokine CCL5 / metabolism
  • Drug Interactions
  • Drug Therapy, Combination
  • Ethanolamines / therapeutic use*
  • Female
  • Formoterol Fumarate
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Interleukin-8 / metabolism
  • Male
  • Middle Aged
  • Receptors, Adrenergic, beta-2 / metabolism
  • Receptors, Glucocorticoid / metabolism
  • Severity of Illness Index
  • Sputum / chemistry*
  • Sputum / metabolism
  • Tissue Distribution


  • Anti-Asthmatic Agents
  • Bronchodilator Agents
  • Chemokine CCL5
  • Ethanolamines
  • Interleukin-8
  • Receptors, Adrenergic, beta-2
  • Receptors, Glucocorticoid
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Beclomethasone
  • Albuterol
  • Formoterol Fumarate