Distinct cytokine production by lung and blood neutrophils from children with cystic fibrosis
Distinct cytokine production by lung and blood neutrophils from children with cystic fibrosis
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DOI：
10.1152/ajplung.00156.2002
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发表时间：
2003-06-01
影响因子：
4.9
通讯作者：
Clement, A
中科院分区：
文献类型：
--
作者：
Corvol, H;Fitting, C;Clement, A
炎症在囊性纤维化（CF）的肺部疾病进展中起关键作用。这种炎症过程由气道中的中性粒细胞流入主导。为了确定CF患者气道中中性粒细胞的积聚是否与功能改变相关，我们分析了从肺室和血液中分离的中性粒细胞自发和在LPS存在下释放主要中性粒细胞促炎和抗炎细胞因子IL-8和IL-1受体拮抗剂（ra）的能力。比较CF患者和对照组血液中性粒细胞产生的细胞因子，显示CF中性粒细胞释放的IL-8显著增加，IL-1 ra显著减少。CF患者气道和血液中性粒细胞产生细胞因子的比较也记录了不同的特征：气道中性粒细胞自发释放的IL-8和IL-1 ra显着高于血液中性粒细胞的释放。在LPS存在下的培养未能进一步增强细胞因子的产生。对地塞米松作用的分析证实了CF中肺和血液中性粒细胞反应性的差异。地塞米松（10（-6）M）在有效减少血液中性粒细胞产生IL-8的浓度下使用，不能抑制气道中性粒细胞分泌IL-8。此外，CF患儿和纤毛运动障碍综合征患儿的气道中性粒细胞分泌细胞因子的比较也记录了不同的分泌特征。这些结果与CF中肺和血液中性粒细胞的细胞因子产生失调一致。他们提供了支持的假设，不仅CF基因型，但也局部环境可能会修改中性粒细胞的功能特性。
Inflammation plays a critical role in lung disease progression in cystic fibrosis (CF). This inflammatory process is dominated by a neutrophil influx in the airways. To determine whether the accumulation of neutrophils in the airways of CF patients is associated with an altered function, we analyzed the capacity of neutrophils isolated from the lung compartment and the blood to release the major neutrophil pro- and anti-inflammatory cytokines IL-8 and IL-1-receptor antagonist (ra) spontaneously and in the presence of LPS. Comparison of cytokine production by blood neutrophils from CF patients and from control subjects showed significantly increased IL-8 and decreased IL-1ra release by CF neutrophils. Comparison of cytokine production by airway and blood neutrophils from CF patients also documented distinct profiles: the spontaneous release of IL-8 and IL-1ra by airway neutrophils was significantly higher than that from blood neutrophils. Culture in the presence of LPS failed to further enhance cytokine production. Analysis of the effect of dexamethasone confirmed the difference in the responsiveness of lung and blood neutrophils in CF. Used at a concentration effective in reducing IL-8 production by blood neutrophils, dexamethasone (10(-6) M) was unable to repress secretion of IL-8 by airway neutrophils. In addition, comparison of cytokine production by airway neutrophils from children with CF and children with dyskinetic cilia syndrome also documented distinct profiles of secretion. These results are consistent with a dysregulated cytokine production by lung and blood neutrophils in CF. They provide support to the hypothesis that not only the CF genotype but also the local environment may modify the functional properties of the neutrophils.