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Corticosteroid suppression of lipoxin A4 and leukotriene B4 from 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 microg/ml) with or without dexamethasone (10(-6)M). LTB4 and LXA4 were measured by enzyme immunoassay. RESULTS:LXA4 biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA4 induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTB4 were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTB4 was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTB4 and LXA4, with lesser suppression of LTB4 in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA4 and FEV1 (% predicted) (r(s) = 0.60; p < 0.01). CONCLUSIONS:Decreased LXA4 and increased LTB4 generation plus impaired corticosteroid sensitivity of LPS-induced LTB4 but not of LXA4 support a role for AMs in establishing a pro-inflammatory balance in severe asthma.

journal_name

Respir Res

journal_title

Respiratory research

authors

Bhavsar PK,Levy BD,Hew MJ,Pfeffer MA,Kazani S,Israel E,Chung KF

doi

10.1186/1465-9921-11-71

subject

Has Abstract

pub_date

2010-06-07 00:00:00

pages

71

eissn

1465-9921

issn

1465-993X

pii

1465-9921-11-71

journal_volume

11

pub_type

杂志文章

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