Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease
Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease
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DOI：
10.1164/rccm.200204-298oc
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发表时间：
2003-01-01
影响因子：
24.7
通讯作者：
Barnes, PJ
中科院分区：
文献类型：
--
作者：
Culpitt, SV;Rogers, DF;Barnes, PJ
慢性阻塞性肺疾病（COPD）的特征是呼吸道炎症，其中巨噬细胞是主要炎症细胞，皮质类固醇治疗的疗效存在争议。我们研究了地塞米松对吸烟者和 COPD 患者 (n = 15) 的支气管肺泡灌洗巨噬细胞释放的基础和白细胞介素 (IL)-1β 或香烟烟雾介质 (CSM) 刺激的 IL-8 和粒细胞巨噬细胞集落刺激因子 (GIVII-CSIF) 的影响。 COPD 患者的 IL-8 基础释放量大约是吸烟者的五倍，而各组的 GM-CSF 相似。 IL-1beta 和 CSM 增加了吸烟者和 COPD 患者巨噬细胞释放的 IL-8 和 GM-CSF。地塞米松不会抑制 COPD 患者巨噬细胞的基础或刺激性 IL-8 释放，但会抑制吸烟者的释放。相反，地塞米松抑制基础和IL-1β刺激的GM-CSF释放，但不抑制GSM刺激的释放。我们的结论是，皮质类固醇对慢性阻塞性肺病缺乏疗效可能是由于呼吸道巨噬细胞对类固醇相对不敏感。
Chronic obstructive pulmonary disease (COPD) is characterized by inflammation of the respiratory tract in which macrophages are the predominant inflammatory cell and for which the efficacy of treatment with corticosteroids is controversial. We investigated the effect of dexamethasone on basal and interleukin (IL)-1beta or cigarette smoke media (CSM)-stimulated release of IL-8 and granulocyte macrophage-colony stimulating factor (GIVII-CSIF) by bronchoalveolar lavage macrophages from cigarette smokers and patients with COPD (n = 15). Basal release of IL-8 was approximately fivefold greater in patients with COPD than smokers, whereas GM-CSF was similar for each group. IL-1beta and CSM increased IL-8 and GM-CSF release by macrophages from both smokers and patients with COPD. Dexamethasone did not inhibit basal or stimulated IL-8 release from macrophages from patients with COPD but inhibited release in smokers. In contrast, basal and IL-1beta-stimulated GM-CSF release, but not GSM-stimulated release, was inhibited by dexamethasone. We conclude that the lack of efficacy of corticosteroids in COPD might be due to the relative steroid insensitivity of macrophages in the respiratory tract.