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Báo cáo y học: "Corticosteroid suppression of lipoxin A4 and leukotriene B4from alveolar macrophages in severe asthma"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: "Corticosteroid suppression of lipoxin A4 and leukotriene B4from alveolar macrophages in severe asthma. | Bhavsar et al. Respiratory Research 2010 11 71 http respiratory-research.eom content 11 1 71 RESPIRATORY RESEARCH RESEARCH Open Access Corticosteroid suppression of lipoxin A4 and leukotriene B4from alveolar macrophages in severe asthma Pankaj K Bhavsar 1 Bruce D Levy2 Mark J Hew1 Michael A Pfeffer2 Shamsah Kazani2 Elliot Israel2 and Kian Fan Chung 1 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 gg ml with or without dexamethasone 10-6M . 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 rs 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. Introduction Patients with asthma are usually well-controlled with inhaled corticosteroids CS and long-acting p2-agonists but a minority of patients described as severe asthma continues to experience uncontrolled asthma in spite of these treatments. Patients