Synergistic effect of influenza A virus on endotoxin-induced mortality in rat pups: A potential model for sudden infant death syndrome
Synergistic effect of influenza A virus on endotoxin-induced mortality in rat pups: A potential model for sudden infant death syndrome
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DOI：
10.1203/01.pdr.0000028250.96650.d7
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发表时间：
2002-10-01
影响因子：
3.6
通讯作者：
Germolec, D
中科院分区：
文献类型：
--
作者：
Blood-Siegfried, J;Nyska, A;Germolec, D
婴儿猝死综合症是发达国家新生儿后期死亡的最常见原因。这是一种排除性诊断，发病高峰年龄在2 ~ 6个月之间。这些婴儿中有50%至63%在死亡前就存在上呼吸道感染。我们推测，未成熟的免疫系统可能会被原发性感染改变，从而阻止二次攻击后的保护性反应。为了模拟双重感染，我们使用了一种非致死性的大鼠适应性甲型流感病毒株和亚致死剂量的内毒素来建立一种模型，该模型导致12天大的幼鼠的病理和死亡，类似于死于婴儿猝死综合征的婴儿。仅当满足特定标准（如感染性损伤之间的时间和幼仔的发育年龄）时才会发生死亡。结果表明，死亡率是由快速的全身性休克事件，而不是肺特异性损害。大体病理结果，如肺瘀点和心脏周围的液体血液尸检是一致的婴儿猝死综合征死亡的婴儿。组织学病变，包括内膜下出血和轻度皮质胸腺细胞坏死，发现更严重和频率在双重挑战的动物。大鼠适应性甲型流感病毒接种动物死亡时脾脏中的巨噬细胞亚群显著升高。我们的模型表明，发育中的免疫系统可能会以夸张的方式对第二次免疫挑战做出反应，导致意外死亡。
Sudden infant death syndrome is the most common cause of postneonatal infant mortality in the developed world. It is a diagnosis of exclusion with peak age of incidence between 2 and 6 mo. Fifty to 63% of these infants have a preexisting upper respiratory tract infection before death. We hypothesized that the immature immune system may be altered by a primary infection, preventing a protective response after secondary challenge. To mimic dual infection, we used a nonlethal strain of a rat-adapted influenza A virus and a sublethal dose of endotoxin to establish a model that results in pathology and death in 12-d-old rat pups similar to that seen in infants dying of sudden infant death syndrome. Mortality only occurred when specific criteria such as timing between infectious insults and developmental age of the pup were met. Results suggest that mortality is caused by a rapid systemic shock event rather than lung-specific damage. Gross pathologic findings such as lung petechiae and liquid blood around the heart on necropsy were consistent with those seen in infants dying of sudden infant death syndrome. Histopathologic lesions including subendocardial hemorrhage and mild cortical thymocyte necrosis were found with greater severity and frequency in dually challenged animals. Macrophage subpopulation in rat-adapted influenza A virus-inoculated animals was significantly elevated in the spleen at the time of death. Our model suggests that the developing immune system can be primed to respond in an exaggerated way to a second immune challenge resulting in unexpected death.