Corticosteroid suppression of lipoxin A4and leukotriene B4from alveolar macrophages in severe asthma

Abstract

Background: An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene B4(LTB4), and lipoxin A4(LXA4) production by alveolar macrophages (AMs) and studied the impact of corticosteroids.Methods: 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 (10-6M). LTB4and LXA4were measured by enzyme immunoassay.Results: LXA4biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA4induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTB4were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTB4was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTB4and LXA4, with lesser suppression of LTB4in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA4and FEV1(% predicted) (rs= 0.60; p < 0.01).Conclusions: Decreased LXA4and increased LTB4generation plus impaired corticosteroid sensitivity of LPS-induced LTB4but not of LXA4support a role for AMs in establishing a pro-inflammatory balance in severe asthma. © 2010 Bhavsar et al; licensee BioMed Central Ltd.