Infection & Immunity Medical Investigation Unit (IMI), Hospital Clínico Universitario-IECSCYL, Avda Ramón, y Cajal 3, 47005 Valladolid, Spain.
BMC Infect Dis. 2011 Aug 31;11:232. doi: 10.1186/1471-2334-11-232.
Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients.
Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient.
Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus.
Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.
由 2009 年大流行性流感 A/H1N1 病毒引起的严重疾病的特征是存在高细胞因子血症。细胞因子反应加剧的原因尚不清楚。如前所述，流感病毒的失控复制可能会强烈影响细胞因子的产生。本研究的目的是评估大流行性流感危重症患者宿主细胞因子反应与病毒水平之间的关系。
本研究纳入了 23 例因原发性病毒性肺炎而入住 ICU 的患者。针对流感 M1 基因开发了一种基于定量 PCR 的方法，以定量检测咽拭子中的病毒载量。此外，我们通过使用基于多重分析的方法，系统地评估了宿主对 ICU 入院时病毒感染的细胞因子反应。通过计算 Spearman 相关系数来进行细胞因子水平与病毒载量之间的相关性研究。
15 例患者需要插管和通气，而 8 例患者在 ICU 住院期间不需要机械通气。在 ICU 入院时呼吸状况最差的患者组中，咽拭子中的病毒载量高 300 倍。咽拭子病毒载量与促炎细胞因子 IL-6、IL-12p70、IFN-γ、趋化因子 MIP-1β、GM-CSF、血管生成介质 VEGF 以及免疫调节细胞因子 IL-1ra 的血浆水平直接相关（p<0.05）。相关性研究还表明，这些介质的水平之间存在显著的正相关，表明它们是同时响应病毒而受到调节的。
由 2009 年大流行性流感病毒引起的严重呼吸道疾病的特征是病毒复制与宿主细胞因子反应之间存在直接关联，这揭示了与其他流感亚型（如 H5N1）引起的严重疾病之间存在潜在的致病联系。
