Background: Inhaled lipopolysaccharide (LPS) induces a dose-dependent, acute neutrophilic response in the\r\nairways of healthy volunteers that can be quantified in induced sputum. Chemokines, such as CXCL1 and CXCL8,\r\nplay an important role in neutrophilic inflammation in the lung through the activation of CXCR2 and small molecule\r\nantagonists of these receptors have now been developed. We investigated the effect of AZD8309, a CXCR2\r\nantagonist, compared with placebo on LPS-induced inflammation measured in sputum of healthy volunteers.\r\nMethods: Twenty healthy subjects were randomized in a double-blind placebo-controlled, cross-over study.\r\nAZD8309 (300 mg) or placebo was dosed twice daily orally for 3 days prior to challenge with inhaled LPS and\r\ninduced sputum was collected 6 h later.\r\nResults: Treatment with AZD8309 showed a mean 77% reduction in total sputum cells (p < 0.001) and 79%\r\nreduction in sputum neutrophils (p < 0.05) compared with placebo after LPS challenge. There was also a reduction\r\nin neutrophil elastase activity (p < 0.05) and CXCL1 (p < 0.05) and trends for reductions in sputum macrophages\r\n(47%), leukotriene B4 (39%) and CXCL8 (52%).\r\nConclusions: AZD8309 inhibited LPS-induced inflammation measured in induced sputum of normal volunteers,\r\nindicating that this treatment may be useful in the treatment of neutrophilic diseases of the airways, such as COPD,\r\nsevere asthma and cystic fibrosis.\r\nTrial registration: NCT00860821.
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