大流行性 H1N1 流感病毒感染时细胞因子的强烈诱导，伴有 IL-10 和 IL-6 的大量产生。

Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.

机构信息

Microbiology Laboratory, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People's Republic of China.

出版信息

PLoS One. 2011;6(12):e28680. doi: 10.1371/journal.pone.0028680. Epub 2011 Dec 9.

BACKGROUND

The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1)] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1) are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1) patients and identified cytokines related to disease severity.

METHODS AND PRINCIPAL FINDINGS

We retrieved 77, 59, 26 and 26 sera samples from P(H1N1) and non-flu influenza like illness (non-ILIs) cases with mild symptoms (mild patients), P(H1N1) vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1) and non-ILIs patients with severe symptoms (severe patients). Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1) patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1) patients. Higher IL-10 secretion in P(H1N1) vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression.

CONCLUSION AND SIGNIFICANCE

A comprehensive innate immune response was activated at the early stage of P(H1N1) infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1) patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1) patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression, but the underlying mechanism awaits further detailed investigations.

背景

先天免疫系统通过诱导细胞因子和趋化因子的表达，成为抵抗病毒的第一道防线。许多大流行性 H1N1 流感病毒[P（H1N1）]感染的重症病例发生在 18 岁以下的年轻人中，他们很少受到季节性流感的严重影响。关于 P（H1N1）宿主细胞因子谱的结果喜忧参半。在本研究中，我们调查了 P（H1N1）患者的宿主细胞因子谱，并确定了与疾病严重程度相关的细胞因子。

方法和主要发现

我们分别从 P（H1N1）和非流感样疾病（非 ILI）轻症患者（轻症患者）、P（H1N1）疫苗接种者和健康个体中采集了 77、59、26 和 26 份血清样本，从 P（H1N1）和非 ILI 重症患者（重症患者）中采集了 9 和 16 份血清样本。用细胞因子珠阵列检测白细胞介素 1、白细胞介素 2、白细胞介素 4、白细胞介素 5、白细胞介素 6、白细胞介素 8、白细胞介素 10、白细胞介素 12、干扰素-γ和肿瘤坏死因子-α，用 ELISA 法检测白细胞介素 17 和白细胞介素 23。与健康对照组相比，轻症 P（H1N1）患者产生的白细胞介素 2、白细胞介素 12、干扰素-γ、白细胞介素 6、肿瘤坏死因子-α、白细胞介素 5、白细胞介素 10、白细胞介素 17 和白细胞介素 23 显著升高。而重症 P（H1N1）患者则表现出过度的白细胞介素 6 和白细胞介素 10 产生。在 P（H1N1）疫苗接种者中更高的白细胞介素 10 分泌证实了我们的观察结果，即 P（H1N1）患者血清中白细胞介素 6 和白细胞介素 10 的水平升高可能导致疾病进展。

结论和意义

在 P（H1N1）感染的早期阶段，就激活了全面的先天免疫反应，产生了 Th1/Th2/Th3 细胞因子的组合。随着疾病的进展，重症 P（H1N1）患者中观察到全身产生白细胞介素 6 和白细胞介素 10。进一步的分析发现，重症 P（H1N1）患者中白细胞介素 6 和白细胞介素 10 的产生有很强的相关性。白细胞介素 6 可能作为一种介质诱导白细胞介素 10 的产生。P（H1N1）患者血清中白细胞介素 6 和白细胞介素 10 水平的升高可能导致疾病进展，但潜在机制有待进一步详细研究。