RT Journal Article T1 Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza. A1 Bermejo-Martin, Jesus F A1 Ortiz de Lejarazu, Raul A1 Pumarola, Tomas A1 Rello, Jordi A1 Almansa, Raquel A1 Ramírez, Paula A1 Martin-Loeches, Ignacio A1 Varillas, David A1 Gallegos, Maria C A1 Serón, Carlos A1 Micheloud, Dariela A1 Gomez, Jose Manuel A1 Tenorio-Abreu, Alberto A1 Ramos, María J A1 Molina, M Lourdes A1 Huidobro, Samantha A1 Sanchez, Elia A1 Gordón, Mónica A1 Fernández, Victoria A1 Del Castillo, Alberto A1 Marcos, Ma Angeles A1 Villanueva, Beatriz A1 López, Carlos Javier A1 Rodríguez-Domínguez, Mario A1 Galan, Juan-Carlos A1 Cantón, Rafael A1 Lietor, Aurora A1 Rojo, Silvia A1 Eiros, Jose M A1 Hinojosa, Carmen A1 Gonzalez, Isabel A1 Torner, Nuria A1 Banner, David A1 Leon, Alberto A1 Cuesta, Pablo A1 Rowe, Thomas A1 Kelvin, David J K1 Quimiocinas K1 Citocinas K1 Cartilla de ADN K1 Femenino K1 Pruebas de Inhibición de Hemaglutinación K1 Humanos K1 Subtipo H1N1 del Virus de la Influenza A K1 Gripe Humana K1 Unidades de Cuidados Intensivos K1 Tiempo de Internación K1 Masculino K1 Mediana Edad K1 Selección de Paciente K1 ARN Viral K1 Índice de Severidad de la Enfermedad K1 Células TH1 K1 Carga Viral K1 Adulto AB INTRODUCTIONHuman 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.METHODSWe 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.RESULTSIncreased 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.CONCLUSIONSWhile 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. PB BIOMED CENTRAL LTD SN 1364-8535 YR 2009 FD 2009-12-11 LK http://hdl.handle.net/10668/1670 UL http://hdl.handle.net/10668/1670 LA en NO Bermejo-Martin JF, Ortiz de Lejarazu R, Pumarola T, Rello J, Almansa R, Ramírez P, et al. Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza. Crit Care. 2009; 13(6):R201 NO Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; DS RISalud RD Apr 6, 2025