Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza

被引:294
作者
Bermejo-Martin, Jesus F. [1 ,2 ]
Ortiz de Lejarazu, Raul [1 ,2 ]
Pumarola, Tomas [3 ]
Rello, Jordi [4 ]
Almansa, Raquel [1 ,2 ]
Ramirez, Paula [5 ]
Martin-Loeches, Ignacio [4 ]
Varillas, David [1 ,2 ]
Gallegos, Maria C. [6 ]
Seron, Carlos [7 ]
Micheloud, Dariela [8 ,9 ]
Manuel Gomez, Jose [8 ,9 ]
Tenorio-Abreu, Alberto [10 ]
Ramos, Maria J. [10 ]
Lourdes Molina, M. [11 ]
Huidobro, Samantha [12 ]
Sanchez, Elia [13 ]
Gordon, Monica [5 ]
Fernandez, Victoria [6 ]
del Castillo, Alberto [14 ]
Angeles Marcos, Ma [14 ]
Villanueva, Beatriz [15 ]
Javier Lopez, Carlos [15 ]
Rodriguez-Dominguez, Mario [16 ,17 ]
Galan, Juan-Carlos [16 ,17 ]
Canton, Rafael [16 ,17 ]
Lietor, Aurora [18 ]
Rojo, Silvia [1 ,2 ]
Eiros, Jose M. [1 ,2 ]
Hinojosa, Carmen [19 ]
Gonzalez, Isabel [19 ]
Torner, Nuria [20 ,21 ]
Banner, David [22 ]
Leon, Alberto [23 ]
Cuesta, Pablo [24 ]
Rowe, Thomas [22 ,25 ]
Kelvin, David J. [22 ,23 ,25 ]
机构
[1] Hosp Clin Univ Valladolid, Natl Ctr Influenza, Valladolid 47005, Spain
[2] Hosp Clin Univ Valladolid, Unidad Invest Infecc & Inmunidad, IECSCYL, Microbiol Serv, Valladolid 47005, Spain
[3] Hosp Clin Barcelona, Virol Lab, E-08036 Barcelona, Spain
[4] Joan XXIII Univ Hosp CIBERes Enfermedades Resp II, Crit Care Dept, Tarragona 43007, Spain
[5] Hosp Univ La Fe, Crit Care Dept, Valencia 46009, Spain
[6] Hosp Son Llatzer, Microbiol Serv, Palma de Mallorca 07198, Spain
[7] Hosp Gen San Jorge, Intens Care Unit, Huesca 22004Y, Spain
[8] Hosp Gen Gregorio Maranon, Intens Care Unit, Madrid 28007, Spain
[9] Hosp Gen Gregorio Maranon, Internal Med Serv, Madrid 28007, Spain
[10] Hosp Univ Canarias, Microbiol Serv, Santa Cruz De Tenerifey 38009, Spain
[11] Hosp Gen La Palma, Microbiol Serv, Brena Alta 38713, Spain
[12] Hosp Univ Canarias, Intens Care Unit, Santa Cruz De Tenerifey 38009, Spain
[13] Hosp Virgen Rocio, Intens Care Unit, Seville 41013, Spain
[14] Hosp Son Llatzer, Intens Care Unit Serv, Palma de Mallorca 07198, Spain
[15] Hosp Lozano Blesa, Intens Care Unit Serv, Zaragoza 50009, Spain
[16] Hosp Univ Ramon y Cajal, Microbiol Serv, Madrid 28049, Spain
[17] CIBERESP, Madrid 28049, Spain
[18] Hosp Univ Ramon y Cajal, Intens Care Unit, Madrid 28049, Spain
[19] Hosp Clin Univ, Infect Dis Serv, Valladolid 47005, Spain
[20] Hosp Univ Valle Hebron, Prevent Med Serv, Barcelona 08035, Spain
[21] CIBERESP, Barcelona 08035, Spain
[22] Univ Hlth Network, Div Expt Therapeut, Toronto, ON M5G 1L7, Canada
[23] Shantou Univ, Int Inst Infect & Immun, Shantou 515031, Guangdong, Peoples R China
[24] Hosp Villarobredo, Intens Care Unit, Villarrobledo 02600, Spain
[25] Univ Toronto, Dept Immunol, Toronto, ON M5G 1L7, Canada
来源
CRITICAL CARE | 2009年 / 13卷 / 06期
关键词
H1N1; INFLUENZA; T-CELLS; IMMUNE-RESPONSES; PUBLIC-HEALTH; T(H)17 CELLS; IN-VIVO; VIRUS; INFECTION; CYTOKINE; EXPRESSION;
D O I
10.1186/cc8208
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Introduction 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. Methods 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. Results Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1 beta), 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. Conclusions 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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页数:11
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