Effect of formoterol and budesonide on chemokine release, chemokine receptor expression and chemotaxis in human neutrophils

Severe persistent asthma and chronic obstructive pulmonary disease (COPD) are associated with neutrophil influx into the airways. It is not clear whether neutrophil chemotaxis is influenced by β2-agonists and glucocorticoids, drugs commonly used in treatment of asthma and COPD. The effect of a long-acting β2-agonist (formoterol), and a glucocorticosteroid (budesonide) on chemokine/cytokine release (CXCL8, CXCL1, IL-6), regulation of chemokine receptors (CXCR1, CXCR2), and migration were assessed in neutrophils from 10 non-allergic, healthy donors. Formoterol enhanced and budesonide inhibited IL-6, CXCL8 and CXCL1 release from LPS-stimulated neutrophils. Formoterol up-regulated both CXCR1 and CXCR2 expression, whereas budesonide up-regulated the expression of CXCR2 only. Despite the effects on chemokine release and drug-induced up-regulation of CXCR1 and CXCR2, no influence on neutrophil chemotaxis could be demonstrated.We conclude that a β2-agonist and a glucocorticoid, commonly used in the treatment of obstructive lung diseases, influence chemokine release and receptor sensitivity but the functional consequences of these findings remain unclear.