Fast beneficial systemic anti-inflammatory effects of inhaled budesonide and formoterol on circulating lymphocytes in asthma

BACKGROUND AND OBJECTIVE: Inhaled glucocorticoids and long acting beta2 -agonists reduce airway inflammation. It is unclear if this effect is based on the local action of the drugs or is due to a systemic effect on circulating peripheral blood lymphocytes. We assessed whether inhaled budesonide and/or formoterol modify the activity of circulating peripheral blood lymphocytes. METHODS: Placebo controlled crossover design, including healthy (n = 10) or mild asthmatic males (n = 8). Blood was collected in the morning at 08:00 before drug inhalation, and drugs (placebo, budesonide 400 mug, formoterol 12 mug) were inhaled alone or in combination at 08:30. Four more blood samples were collected after inhalation at 09:00, 09:30, 12:30 and at 09:30 am on the following day. The activity of the glucocorticoid receptor, NFkappaB and IkappaB was determined in isolated lymphocytes. Lymphocytes were stimulated with lipopolysaccharide (LPS 10 mug/mL) for 24 h and interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, eotaxin level were determined. Lymphocyte proliferation was induced by phytohaemagglutinin (PHA 10 mug/mL) over 24 h. RESULTS: When combined, the drugs synergistically activated the glucocorticoid receptor within 30 min but did not modify NFkappaB or IkappaB activity. Inhaled budesonide significantly reduced LPS-induced IL-1beta, IL-6, IL-8 and TNF-alpha secretion, while inhaled formoterol had no such effect; however when combined, the inhibitory effect of budesonide was significantly increased by formoterol. PHA-induced proliferation was reduced by both drugs alone and in combination. CONCLUSIONS: Combined budesonide and formoterol may reduce airway inflammation and immune reactivity of circulating lymphocytes through its local and systemic effects