TY - JOUR T1 - Effects of formoterol and salmeterol on cytokine release from monocyte-derived macrophages JF - European Respiratory Journal JO - Eur Respir J SP - 178 LP - 186 DO - 10.1183/09031936.00158008 VL - 36 IS - 1 AU - L.E. Donnelly AU - S.J. Tudhope AU - P.S. Fenwick AU - P.J. Barnes Y1 - 2010/07/01 UR - http://erj.ersjournals.com/content/36/1/178.abstract N2 - Pulmonary macrophages are a target for inhaled therapies. Combinations of long-acting β2-agonists (LABA) and glucocorticosteroids have been developed for asthma and chronic obstructive pulmonary disease (COPD). This study examined two LABA, salmeterol and formoterol, and the glucocorticosteroid, budesonide, on cytokine release from monocyte-derived macrophages (MDM) to determine whether anti-inflammatory effects observed in patients are due to inhibition of macrophages. MDM were incubated in the absence or presence of LABA or budesonide prior to stimulation with lipopolysaccharide (LPS). Tumour necrosis factor (TNF)-α, granulocyte macrophage-colony stimulating factor (GM-CSF) and CXC chemokine ligand (CXCL)8 were measured by ELISA. Formoterol and salmeterol inhibited LPS-stimulated release of TNF-α (mean effective concentration (EC50) 2.4±1.8 and 3.5±2.7 nM, respectively; n = 11–16), GM-CSF (EC50 24.6±2.1 and 52.4±40.8 nM, respectively, n = 11–12) but not CXCL8 from LPS-stimulated MDM. Budesonide inhibited release of all three cytokines (EC50 TNF-α: 1.2±0.4 nM; GM-CSF: 0.4±0.2 nM; CXCL8: 0.4±0.1 nM; n = 3–4). Formoterol but not salmeterol elevated cAMP in these cells. These effects were attenuated by β-adrenoceptor antagonists, propranolol and ICI118551. Salmeterol (10−7 M) also inhibited formoterol-induced cAMP and formoterol-mediated attenuation of cytokine release. Combining budesonide (0.3 nM) with formoterol, inhibited TNF-α release additively. LABA may inhibit inflammatory cytokine release from macrophages in a cAMP-independent manner and act additively with budesonide. ER -