Low-dose interferon-α treatment improves survival and inflammatory responses in a mouse model of fulminant acute respiratory distress syndrome.

Low-dose interferon-α treatment improves survival and inflammatory responses in a mouse model of fulminant acute respiratory distress syndrome.
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DOI:
10.1007/s10753-013-9607-1
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发表时间:
2013-08
期刊:
影响因子:
5.1
通讯作者:
Kawakami K
Kawakami K
中科院分区:
医学2区
文献类型:
--
作者:
Kudo D;Uno K;Aoyagi T;Akahori Y;Ishii K;Kanno E;Maruyama R;Kushimoto S;Kaku M;Kawakami K

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急性呼吸窘迫综合征(ARDS)是由多种疾病引起的严重肺部炎症。尽管症状严重,但这种病理状况的治疗策略仍然很差。干扰素(IFN)-α是一种抗病毒细胞因子,小剂量IFN-α有抗病毒作用。因此,我们研究了这种细胞因子如何影响小鼠模型中的ARDS。C57 BL/6小鼠经气管内连续给予α-半乳糖神经酰胺(α-GalCer)和脂多糖(LPS),导致暴发性ARDS的发生。然后用IFN-α鼻内给药这些小鼠,并评价其存活率、肺重量、病理学发现和细胞因子产生。给予低剂量IFN-α可延长暴发性ARDS小鼠的存活时间,但高剂量IFN-α则无此作用。组织学分析显示,低剂量IFN-α治疗改善了暴发性ARDS小鼠弥漫性肺泡损伤的发现,这与湿/干(W/D)肺重量比的降低有关。此外,与对照组小鼠相比,IFN-α治疗组小鼠肺中IFN-γ的产生显著减少,但两组的肿瘤坏死因子(TNF)-α的产生几乎相等。低剂量IFN-α在暴发性ARDS小鼠模型中显示出抑制和治疗作用,肺中IFN-γ的产生减少可能与这种治疗的有益作用有关。
Acute respiratory distress syndrome (ARDS) is accompanied by severe lung inflammation induced by various diseases. Despite the severity of symptoms, therapeutic strategies for this pathologic condition are still poorly developed. Interferon (IFN)-α is well known as an antiviral cytokine and low-dose IFN-α has been reported to show antiinflammatory effects. Therefore, we investigated how this cytokine affected ARDS in a mouse model. C57BL/6 mice received sequential intratracheal administration of α-galactosylceramide (α-GalCer) and lipopolysaccharide (LPS), which resulted in the development of fulminant ARDS. These mice were then treated intranasally with IFN-α and their survival, lung weight, pathological findings, and cytokine production were evaluated. Administration of low-dose IFN-α prolonged survival of fulminant ARDS mice, but higher doses of IFN-α did not. Histological analysis showed that low-dose IFN-α treatment improved findings of diffuse alveolar damage in fulminant ARDS mice, which was associated with reduction in the wet/dry (W/D) lung weight ratio. Furthermore, IFN-γ production in the lungs was significantly reduced in IFN-α-treated mice, compared with control mice, but tumor necrosis factor (TNF)-α production was almost equivalent for both groups. Low-dose IFN-α shows antiinflammatory and therapeutic effects in a mouse model of fulminant ARDS, and reduced production of IFN-γ in the lung may be involved in the beneficial effect of this treatment.
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