Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza.
Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza.
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DOI：
10.1186/cc8208
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kelvin DJ
中科院分区：
文献类型：
--
作者：
Bermejo-Martin JF;Ortiz de Lejarazu R;Pumarola T;Rello J;Almansa R;Ramírez P;Martin-Loeches I;Varillas D;Gallegos MC;Serón C;Micheloud D;Gomez JM;Tenorio-Abreu A;Ramos MJ;Molina ML;Huidobro S;Sanchez E;Gordón M;Fernández V;Del Castillo A;Marcos MA;Villanueva B;López CJ;Rodríguez-Domínguez M;Galan JC;Cantón R;Lietor A;Rojo S;Eiros JM;Hinojosa C;Gonzalez I;Torner N;Banner D;Leon A;Cuesta P;Rowe T;Kelvin DJ
人类宿主感染甲型H1N1流感病毒新变种（nvH 1 N1）后的免疫反应知之甚少。我们在这里利用全身细胞因子和抗体水平在早期免疫反应的差异，在轻度和重度患者感染nvH 1 N1的评估。我们分析了29种细胞因子和趋化因子，并评估了nvH 1 N1感染患者的两个队列中，症状发作后的前五天内获得的血清中宿主免疫应答的定量和定性测量的血凝抑制活性。重度患者因呼吸功能不全需要住院治疗（n = 20）（其中10例患者入住重症监护室），而轻度患者仅具有流感样症状（n = 15）。另取健康献血员15例作为对照组。使用非参数U-Mann Whitney检验评估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。通过使用靶向神经氨酸酶基因的实时PCR在血清中进行病毒载量。先天免疫介质（IP-10、MCP-1、MIP-1β）水平升高和抗nvH 1 N1抗体缺失是住院患者和轻度患者对nvH 1 N1感染的早期应答的特征。仅在住院患者中发现了高全身水平的II型干扰素（IFN-γ）以及一组参与T辅助细胞17（IL-8、IL-9、IL-17、IL-6）和T辅助细胞1（TNF-α、IL-15、IL-12 p70）反应的介质。IL-15、IL-12 p70、IL-6在本研究中构成了危重病的标志。IL-6、IL-8与危重患者PaO 2呈负相关。虽然nvH 1 N1感染在轻度和重度患者中均诱导典型的先天性应答，但伴有呼吸系统受累的重度疾病的特征在于Th 17和Th 1细胞因子的早期分泌，这些细胞因子通常与细胞介导的免疫相关，但也通常与自身免疫性/炎性疾病的发病机制相关。Th 1和Th 17介质在nvH 1 N1轻度和重度疾病演变中的确切作用值得进一步研究，以确定这些细胞因子在重度疾病中发挥的有害或有益作用。
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-1β), 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-γ) 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-α, 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.
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影响因子：
5
作者：
Cameron MJ;Bermejo-Martin JF;Danesh A;Muller MP;Kelvin DJ
通讯作者：
Kelvin DJ
DOI：
10.4049/jimmunol.0801814
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamada H;Garcia-Hernandez Mde L;Reome JB;Misra SK;Strutt TM;McKinstry KK;Cooper AM;Swain SL;Dutton RW
通讯作者：
Dutton RW
影响因子：
6.2
作者：
Garulli, Bruno;Castrucci, Maria R.
通讯作者：
Castrucci, Maria R.
影响因子：
14.2
作者：
Louten, Jennifer;Boniface, Katia;Malefyt, Rene de Waal
通讯作者：
Malefyt, Rene de Waal
DOI：
10.4049/jimmunol.0900995
发表时间：
2009-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Crowe CR;Chen K;Pociask DA;Alcorn JF;Krivich C;Enelow RI;Ross TM;Witztum JL;Kolls JK
通讯作者：
Kolls JK