National Centre of Influenza, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
Crit Care. 2009;13(6):R201. doi: 10.1186/cc8208. Epub 2009 Dec 11.
Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1.
We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene.
Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1beta), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-gamma) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-alpha, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients.
While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.
目前对于感染新型 A/H1N1 大流行流感病毒（nvH1N1）的人体宿主免疫反应知之甚少。本研究通过检测细胞因子和抗体水平，评估了 nvH1N1 轻症和重症患者早期免疫反应的差异。
我们分析了 29 种细胞因子和趋化因子，并在症状出现后 5 天内，通过血凝抑制活性（作为宿主免疫反应的定量和定性测量）评估血清中的宿主免疫反应。我们对两组 nvH1N1 感染患者进行了研究，重症患者（n=20）因呼吸功能不全需要住院治疗（其中 10 例入住重症监护病房），轻症患者仅有流感样症状（n=15）。健康对照组（n=15）也包含在研究中。使用非参数 U-曼惠特尼检验评估各组间介质水平的差异。通过计算斯皮尔曼相关系数确定变量之间的关联。通过针对神经氨酸酶基因的实时 PCR 检测血清中的病毒载量。
固有免疫介质（IP-10、MCP-1、MIP-1beta）水平升高，且无抗 nvH1N1 抗体，这是 nvH1N1 感染后轻症和重症患者早期反应的特征。高水平的 II 型干扰素（IFN-γ）以及一组参与 Th17（IL-8、IL-9、IL-17、IL-6）和 Th1（TNF-α、IL-15、IL-12p70）反应发展的介质也仅在住院患者中发现。IL-15、IL-12p70、IL-6 是本研究中危重症的标志。在危重症患者中，IL-6、IL-8 与 PaO2 呈显著负相关。
虽然 nvH1N1 感染会在轻症和重症患者中引起典型的固有免疫反应，但伴有呼吸受累的重症疾病的特征是早期分泌 Th17 和 Th1 细胞因子，这些细胞因子通常与细胞介导的免疫有关，但也与自身免疫/炎症性疾病的发病机制有关。Th1 和 Th17 介质在 nvH1N1 轻症和重症疾病演变中的确切作用值得进一步研究，以了解这些细胞因子在重症疾病中是有益还是有害。
