9 research outputs found
Corticosteroid suppression of lipoxin A4 and leukotriene B4from alveolar macrophages in severe asthma
<p>Abstract</p> <p>Background</p> <p>An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene B<sub>4 </sub>(LTB<sub>4</sub>), and lipoxin A<sub>4 </sub>(LXA<sub>4</sub>) production by alveolar macrophages (AMs) and studied the impact of corticosteroids.</p> <p>Methods</p> <p>AMs obtained by fiberoptic bronchoscopy from 14 non-asthmatics, 12 non-severe and 11 severe asthmatics were stimulated with lipopolysaccharide (LPS,10 μg/ml) with or without dexamethasone (10<sup>-6</sup>M). LTB<sub>4 </sub>and LXA<sub>4 </sub>were measured by enzyme immunoassay.</p> <p>Results</p> <p>LXA<sub>4 </sub>biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA<sub>4 </sub>induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTB<sub>4 </sub>were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTB<sub>4 </sub>was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTB<sub>4 </sub>and LXA<sub>4</sub>, with lesser suppression of LTB<sub>4 </sub>in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA<sub>4 </sub>and FEV<sub>1 </sub>(% predicted) (r<sub>s </sub>= 0.60; p < 0.01).</p> <p>Conclusions</p> <p>Decreased LXA<sub>4 </sub>and increased LTB<sub>4 </sub>generation plus impaired corticosteroid sensitivity of LPS-induced LTB<sub>4 </sub>but not of LXA<sub>4 </sub>support a role for AMs in establishing a pro-inflammatory balance in severe asthma.</p