Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome

Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome
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DOI:
10.1111/j.1440-1843.2006.00942.x
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发表时间:
2006-11-01
期刊:
影响因子:
6.9
通讯作者:
Yang, Pan-Chyr
Yang, Pan-Chyr
中科院分区:
医学2区
文献类型:
--
作者:
Chien, Jung-Yien;Hsueh, Po-Ren;Yang, Pan-Chyr

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目的和背景:严重急性呼吸综合征(SARS)的病理变化提示SARS后遗症与细胞因子和趋化因子的产生失调有关。为了更好地了解SARS相关肺损伤的免疫病理过程,我们根据肺部受累程度,比较了SARS患者与社区获得性肺炎(CAP)患者血清中细胞因子/趋化因子谱的时间变化。方法:对14例SARS患者和24例CAP患者的血清中11种细胞因子和趋化因子的水平进行了连续检测。选取12名健康受试者的血清作为正常对照。结果:SARS感染期间血清干扰素γ诱导蛋白-10 (IP-10)、IL-2、IL-6水平显著升高。在CAP患者中,而非SARS患者中,干扰素- γ、IL-10、IL-8和干扰素- γ (MIG)诱导的单因子水平与健康对照组相比显著升高。在趋化因子/细胞因子中,IL-6水平与影像学评分相关性最强(r = 0.62)。IP-10和IL-2的升高早于胸部受累的发展,并比影像学评分更早达到峰值。相比之下,IL-6、c反应蛋白和中性粒细胞的动态变化与影像学评分的变化是同步的。SARS患者IL-6与IL-10的平均比值(4.84,范围0.41 ~ 21)显著高于CAP患者(2.95,范围0.02 ~ 10.57)(P = 0.04)。结论:IP-10和IL-2的早期诱导以及随后IL-6的过量产生和IL-10的缺乏可能参与了SARS肺损伤的主要免疫病理过程。这些细胞因子/趋化因子谱的变化与CAP患者观察到的明显不同。
Objective and background: Pathological changes in severe acute respiratory syndrome (SARS) suggest that SARS sequelae are associated with dysregulation of cytokine and chemokine production. To improve understanding of the immuno-pathological processes involved in lung injury associated with SARS, the temporal changes in cytokine/chemokine profiles in the sera of SARS patients were compared with those of patients with community-acquired pneumonia (CAP), according to the degree of lung involvement.Methods: Serum levels of 11 cytokines and chemokines, in 14 patients with SARS and 24 patients with CAP, were serially checked using a bead-based multiassay system. Sera from 12 healthy subjects were used as normal controls.Results: The serum levels of interferon-gamma-inducible protein-10 (IP-10), IL-2 and IL-6 were significantly elevated during SARS infection. In patients with CAP, but not in those with SARS, the levels of interferon-gamma, IL-10, IL-8 and monokine induced by interferon-gamma (MIG) were significantly elevated compared with the levels in healthy controls. Among the chemokines/cytokines, IL-6 levels correlated most strongly with radiographic scores (r = 0.62). The elevation of IP-10 and IL-2 antedated the development of chest involvement and reached peak levels earlier than the radiographic scores. In contrast, the dynamic changes in IL-6, C-reactive protein and neutrophils occurred synchronously with the changes in radiographic scores. The mean ratio of IL-6 to IL-10 in SARS patients (4.84; range 0.41-21) was significantly higher than that in CAP patients (2.95; range 0.02-10.57) (P = 0.04).Conclusions: The early induction of IP-10 and IL-2, as well as the subsequent over-production of IL-6 and lack of IL-10 production, probably contribute to the main immuno-pathological processes involved in lung injury in SARS. These changes in cytokine/chemokine profile are remarkably different from those observed in CAP patients.