The Protective Effects of Intranasal Administration of IL-12 Given Before Influenza Virus Infection and the Negative Effects of IL-12 Treatment Given After Viral Infection
The Protective Effects of Intranasal Administration of IL-12 Given Before Influenza Virus Infection and the Negative Effects of IL-12 Treatment Given After Viral Infection
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DOI：
10.1002/jmv.24494
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发表时间：
2016-09-01
影响因子：
12.7
通讯作者：
Tanaka, Kazuo
中科院分区：
文献类型：
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作者：
Ishikawa, Hiroki;Ino, Satoshi;Tanaka, Kazuo
为了研究IL-12的施用是否对流感病毒感染有效，连续三天鼻内施用IL-12，然后用非致死剂量的流感病毒感染小鼠。IL-12处理的小鼠在体重减轻、病毒负荷、促炎细胞因子产生和肺中炎性细胞浸润的缓解方面比对照小鼠对病毒更具抗性。与对照小鼠中观察到的相比，在感染前用IL-12处理的小鼠的肺中NK细胞的数量和NK细胞细胞毒性的水平显著增加，导致迅速消除病毒感染的细胞。出乎意料的是，在感染非致死剂量的病毒后接受IL-12治疗的所有小鼠都因其肺部的高病毒负荷和促炎细胞因子产生而死亡。其机制之一被认为是肺中具有免疫抑制功能的髓源性抑制细胞（MDSC）的激活。因此，IL-12治疗具有相反的效果，这取决于它是在感染之前还是之后施用。这些结果证明了免疫调节治疗的潜在风险，例如给予外源性细胞因子或中和细胞因子。(C)2016 Wiley Periodicals，Inc.
To investigate whether the administration of IL-12 is effective against influenza virus infection, mice were intranasally administered IL-12 for three consecutive days and then infected with a non-lethal dose of the influenza virus. The IL-12-treated mice were more resistant to the virus than control mice with respect to the remission of body weight loss, virus burden, pro-inflammatory cytokine production, and inflammatory cell infiltration in the lungs. The number of NK cells and the level of NK cell cytotoxicity significantly increased in the lungs of the mice treated with IL-12 before infection compared to that observed in control mice, leading to promptly eliminate the viral-infected cells. Unexpectedly, all of mice that received IL-12 treatment after being infected with a non-lethal dose of the virus died as a result of their high virus burden and pro-inflammatory cytokine production in the lungs. One possibility of the mechanisms was considered to be activation of myeloid-derived suppressor cell (MDSC), which has immune suppressive function, in the lungs. Thus, IL-12 treatment has opposite effects depending on whether it is administered before or after infection. These results demonstrate the potential risks of immune modulating therapies such as administration of exogenous cytokine or neutralization of cytokine. (C) 2016 Wiley Periodicals, Inc.