IL-1β is a key cytokine that induces trypsin upregulation in the influenza virus-cytokine-trypsin cycle.
IL-1β is a key cytokine that induces trypsin upregulation in the influenza virus-cytokine-trypsin cycle.
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DOI：
10.1007/s00705-016-3093-3
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发表时间：
2017-01
影响因子：
2.7
通讯作者：
Kido H
中科院分区：
文献类型：
--
作者：
Indalao IL;Sawabuchi T;Takahashi E;Kido H
重症流感以细胞因子风暴为特征，流感病毒-细胞因子-胰蛋白酶循环是病毒增殖和多器官衰竭的重要机制之一。本研究的目的是确定负责胰蛋白酶上调的关键细胞因子。小鼠感染流感病毒株 A/Puerto Rico/8/34 (H1N1)，或单独治疗或联合使用白细胞介素 1β、白细胞介素 6 和肿瘤坏死因子 α 进行治疗。监测肺中这些细胞因子和胰蛋白酶的水平。研究了抗 IL-1β 抗体对人 A549 细胞中细胞因子和胰蛋白酶表达以及受感染小鼠肺部炎症的中和作用。感染以剂量和时间依赖性方式诱导小鼠肺部产生白细胞介素 1β、白细胞介素 6、肿瘤坏死因子 α 和异位胰蛋白酶。腹腔内给予白细胞介素-1β与其他细胞因子组合往往会上调肺部的胰蛋白酶和细胞因子的表达，但不含白细胞介素-1β的组合不会诱导胰蛋白酶的产生。相比之下，A549 细胞单独与白细胞介素 1β 一起孵育可诱导细胞因子和胰蛋白酶，而抗白细胞介素 1β 抗体治疗消除了这些作用。对受感染的小鼠施用抗体减少了肺部炎症面积。这些发现表明 IL-1β 在胰蛋白酶上调中发挥关键作用，并在多器官衰竭中发挥病理作用。
Severe influenza is characterized by a cytokine storm, and the influenza virus–cytokine–trypsin cycle is one of the important mechanisms of viral multiplication and multiple organ failure. The aim of this study was to define the key cytokine(s) responsible for trypsin upregulation. Mice were infected with influenza virus strain A/Puerto Rico/8/34 (H1N1) or treated individually or with a combination of interleukin-1β, interleukin-6, and tumor necrosis factor α. The levels of these cytokines and trypsin in the lungs were monitored. The neutralizing effects of anti-IL-1β antibodies on cytokine and trypsin expression in human A549 cells and lung inflammation in the infected mice were examined. Infection induced interleukin-1β, interleukin-6, tumor necrosis factor α, and ectopic trypsin in mouse lungs in a dose- and time-dependent manner. Intraperitoneal administration of interleukin-1β combined with other cytokines tended to upregulate trypsin and cytokine expression in the lungs, but the combination without interleukin-1β did not induce trypsin. In contrast, incubation of A549 cells with interleukin-1β alone induced both cytokines and trypsin, and anti-interleukin-1β antibody treatment abrogated these effects. Administration of the antibody in the infected mice reduced lung inflammation area. These findings suggest that IL-1β plays a key role in trypsin upregulation and has a pathological role in multiple organ failure.