Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/16844
Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza
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AuthorBermejo-Martin, Jesus F.; Ortiz de Lejarazu, Raul; Pumarola, Tomas; Rello, Jordi; Almansa, Raquel; Ramirez, Paula; Martin-Loeches, Ignacio; Varillas, David; Gallegos, Carmen; Seron, Carlos; Micheloud, Dariela; Manuel Gomez, Jose; Tenorio-Abreu, Alberto; Ramos, Maria J.; Lourdes Molina, M.; Huidobro, Samantha; Sanchez, Elia; Gordon, Monica; Fernandez, Victoria; del Castillo Blanco, Alberto ; Angeles Marcos, Ma; Villanueva, Beatriz; Javier Lopez, Carlos; Rodriguez-Dominguez, Mario; Galán, Juan Carlos; Canton, Rafael; Lietor, Aurora; Rojo, Silvia; Eiros, Jose M.; Hinojosa, Carmen; Gonzalez, Isabel; Torner, Nuria; Banner, David; Leon, Alberto; Cuesta, Pablo; Rowe, Thomas; Kelvin, David J.
Document typeresearch article
CitationBermejo-Martin JF, Ortiz De Lejarazu R, Pumarola T, Rello J, Almansa R, Ramirez P, et al. Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza. Crit Care. 2009;13(6):R201. Epub 2009 Dec 11.
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.
Length of Stay
Hemagglutination Inhibition Tests
Intensive Care Units
Severity of Illness Index
Influenza A Virus, H1N1 Subtype
DeCSSelección de Paciente
Cartilla de ADN
Pruebas de Inhibición de Hemaglutinación
Unidades de Cuidados Intensivos
Tiempo de Internación
Subtipo H1N1 del Virus de la Influenza A
Persona de Mediana Edad
Índice de Severidad de la Enfermedad