CCL18 as an indicator of pulmonary fibrotic activity in idiopathic interstitial pneumonias and systemic sclerosis
CCL18 as an indicator of pulmonary fibrotic activity in idiopathic interstitial pneumonias and systemic sclerosis
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DOI：
10.1002/art.22559
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发表时间：
2007-05-01
影响因子：
--
通讯作者：
Mueller-Quernheirn, Joachim
中科院分区：
文献类型：
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作者：
Prasse, Antje;Pechkovsky, Dmitri V.;Mueller-Quernheirn, Joachim
目标。在弥漫性肺实质疾病中，肺纤维化的发展往往是毁灭性的，并可能导致死亡。本研究评估了CCL18作为特发性间质性肺炎（IIP’s）和系统性硬化症（SSc）累及肺部的疾病活动性生物标志物的作用。在43例IIPs患者、12例SSc患者和23例健康对照者的培养支气管肺泡灌洗（BAL）细胞上清液、BAL液和血清样本中评估CCL18。采用酶联免疫吸附法检测CCL18的浓度，流式细胞术检测CCL18的表达。所有肺纤维化患者的CCL18浓度均有统计学显著升高。肺泡细胞自发生成CCL18与肺总容量和一氧化碳扩散能力呈负相关，而CCL18浓度与肺泡中性粒细胞和嗜酸性粒细胞计数呈正相关。流式细胞术显示纤维化肺疾病患者CCL18阳性肺泡巨噬细胞百分比增加，每个细胞CCL18荧光强度增加。在一组随访至少6个月的患者中（n = 40），观察到预测总肺活量的变化与CCL18血清浓度的变化之间存在密切的负相关。这些结果表明，BAL细胞产生的CCL18和血清CCL18浓度反映了IIPs患者和SSc患者的肺纤维化活动。监测CCL18产生的变化可能是临床实践和旨在评估纤维化肺疾病治疗新方法的研究中非常有用的工具。
Objective. In diffuse parenchymal lung diseases, the evolution of pulmonary fibrosis is often devastating and may result in death. In this study the role of CCL18 as a biomarker of disease activity in idiopathic interstitial pneumonias (IIP's) and systemic sclerosis (SSc) with lung involvement was evaluated.Methods. CCL18 was assessed in supernatants of cultured bronchoalveolar lavage (BAL) cells as well as BAL fluid and serum samples from 43 patients with IIPs, 12 patients with SSc, and 23 healthy control subjects. Concentrations of CCL18 were measured by enzyme-linked immunosorbent assay, and expression of CCL18 was assessed by flow cytometry.Results. CCL18 concentrations were statistically significantly increased in all patients with fibrotic lung diseases. Spontaneous CCL18 production by BAL cells was negatively correlated with total lung capacity and the diffusion capacity for carbon monoxide, whereas there was a positive correlation of CCL18 concentrations with BAL neutrophil and eosinophil cell counts. Flow cytometry revealed an increase in the percentage of CCL18-positive alveolar macrophages and an increase in the CCL18 fluorescence intensity per cell in patients with fibrotic lung diseases. In a cohort of patients who were followed up for at least 6 months (n = 40), a close negative correlation was observed between changes in the predicted total lung capacity and changes in CCL18 serum concentrations.Conclusion. These findings suggest that CCL18 production by BAL cells and serum CCL18 concentrations reflect pulmonary fibrotic activity in patients with IIPs and those with SSc. Monitoring changes in CCL18 production might be an extraordinarily useful tool in clinical practice and in studies aimed at evaluating new approaches for treatment of fibrotic lung diseases.