Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults.
Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults.
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DOI：
10.1371/journal.pone.0026050
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hui DS
中科院分区：
文献类型：
--
作者：
Lee N;Wong CK;Chan PK;Chan MC;Wong RY;Lun SW;Ngai KL;Lui GC;Wong BC;Lee SK;Choi KW;Hui DS
研究不同病毒亚型引起的严重流感感染中细胞因子/趋化因子的反应可以提高对发病机制的理解。研究对象为因实验室确诊的2009年季节性和大流行性甲型H1N1流感（pH 1 N1）而住院的成人。13种细胞因子/趋化因子的血浆浓度在介绍时测量，然后连续使用流式细胞术和ELISA的流式细胞仪珠阵列。使用离体培养（全血测定，土PHA/LPS刺激）研究来自流感患者的PBMC的细胞因子/趋化因子表达。前瞻性记录和分析临床变量。对63例pH 1 N1流感患者和53例季节性流感患者进行了研究。pH 1 N1患者年龄较轻（平均值±S.D.）。42.8±19.2 vs 70.5±16.7岁），合并症较少。呼吸/心血管并发症在两组中均很常见（71.4% vs 81.1%），尽管pH 1 N1的重度肺炎伴低氧血症（54.0% vs 28.3%）和ICU入院（25.4% vs 1.9%）更常见。促炎细胞因子IL-6、CXCL 8/IL-8、CCL 2/MCP-1和sTNFR-1的过度活化在pH 1 N1肺炎（正常值的2-15倍）和复杂的季节性流感中被发现，但在较轻的pH 1 N1感染中没有。然而，适应性免疫（Th 1/Th 17）相关的CXCL 10/IP-10、CXCL 9/IL-17和IL-17 A在严重的pH 1 N1肺炎中受到明显抑制（比季节性流感低2-27倍; P−值<0.01）。这一模式得到了系列测量的进一步证实。pH 1 N1肺炎中高细胞因子血症倾向于持续，与病毒清除较慢相关[PCR阴性：第3-4天，55% vs 85%;第6-7天，67% vs 100%]。促炎细胞因子升高，尤其是IL-6升高，可预测流感感染患者入住ICU（校正OR 12.6，95%CI 2.6-61.5，每增加1个log 10单位; P = 0.002），并与发热、呼吸急促、脱氧和住院时间相关（斯皮尔曼rho，P值<0.01）。 季节性流感患者的PBMC被激活并在体外表达细胞因子（例如IL-6、CXCL 8/IL-8、CCL 2/MCP-1、CXCL 10/IP-10、CXCL 9/MCP）;它们对刺激的“反应性”显示在疾病过程中动态变化。与季节性流感不同，在严重的pH 1 N1肺炎中发现了一种过度活化的促炎性，但抑制了适应性免疫（Th 1/Th 17）相关的细胞因子反应模式。细胞因子/免疫失调可能在其发病机制中起重要作用。
Studying cytokine/chemokine responses in severe influenza infections caused by different virus subtypes may improve understanding on pathogenesis. Adults hospitalized for laboratory-confirmed seasonal and pandemic 2009 A/H1N1 (pH1N1) influenza were studied. Plasma concentrations of 13 cytokines/chemokines were measured at presentation and then serially, using cytometric-bead-array with flow-cytometry and ELISA. PBMCs from influenza patients were studied for cytokine/chemokine expression using ex-vivo culture (Whole Blood Assay,±PHA/LPS stimulation). Clinical variables were prospectively recorded and analyzed. 63 pH1N1 and 53 seasonal influenza patients were studied. pH1N1 patients were younger (mean±S.D. 42.8±19.2 vs 70.5±16.7 years), and fewer had comorbidities. Respiratory/cardiovascular complications were common in both groups (71.4% vs 81.1%), although severe pneumonia with hypoxemia (54.0% vs 28.3%) and ICU admissions (25.4% vs 1.9%) were more frequent with pH1N1. Hyperactivation of the proinflammatory cytokines IL-6, CXCL8/IL-8, CCL2/MCP-1 and sTNFR-1 was found in pH1N1 pneumonia (2–15 times normal) and in complicated seasonal influenza, but not in milder pH1N1 infections. The adaptive-immunity (Th1/Th17)-related CXCL10/IP-10, CXCL9/MIG and IL-17A however, were markedly suppressed in severe pH1N1 pneumonia (2–27 times lower than seasonal influenza; P−values<0.01). This pattern was further confirmed with serial measurements. Hypercytokinemia tended to be sustained in pH1N1 pneumonia, associated with a slower viral clearance [PCR-negativity: day 3–4, 55% vs 85%; day 6–7, 67% vs 100%]. Elevated proinflammatory cytokines, particularly IL-6, predicted ICU admission (adjusted OR 12.6, 95%CI 2.6–61.5, per log10unit increase; P = 0.002), and correlated with fever, tachypnoea, deoxygenation, and length-of-stay (Spearman's rho, P-values<0.01) in influenza infections. PBMCs in seasonal influenza patients were activated and expressed cytokines ex vivo (e.g. IL-6, CXCL8/IL-8, CCL2/MCP-1, CXCL10/IP-10, CXCL9/MIG); their ‘responsiveness’ to stimuli was shown to change dynamically during the illness course. A hyperactivated proinflammatory, but suppressed adaptive-immunity (Th1/Th17)-related cytokine response pattern was found in severe pH1N1 pneumonia, different from seasonal influenza. Cytokine/immune-dysregulation may be important in its pathogenesis.
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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：
11.8
作者：
Han, Ke;Ma, Huilai;Zeng, Guang
通讯作者：
Zeng, Guang
影响因子：
5.4
作者：
Geiler, Janina;Michaelis, Martin;Cinatl, Jindrich, Jr.
通讯作者：
Cinatl, Jindrich, Jr.
影响因子：
6.4
作者：
Lee, Nelson;Chan, Paul K. S.;Hui, David. S. C.
通讯作者：
Hui, David. S. C.
DOI：
10.1186/cc8208
发表时间：
2009
期刊：
Critical care (London, England)
影响因子：
--
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
通讯作者：
Kelvin DJ