165403 20260108143203.0 doi 10.1186/cc8208 sideral 67971 ART-2009-67971 eng Bermejo-Martin, Jesús F. Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza 2009 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-1ß), 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-¿) 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-a, 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. Access copy available to the general public Unrestricted info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 4.931 2009 CRITICAL CARE MEDICINE 4 / 22 = 0.182 2009 Q1 T1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Ortiz de Lejarazu, Raul Pumarola, Tomás Rello, Jordi Almansa, Raquel Ramírez, Paula Martin-Loeches, Ignacio Varillas, Savid Gallegos, Maria Carmen Serón Arbeloa, Carlos Universidad de Zaragoza (orcid)0000-0002-8068-5016 Micheloud,Daniela Gomez, José Manuel Tenorio-Abreu, Alberto Ramos, María José Molina, Lourdes Huidobro, Samantha Sanchez, Elia Gordón, Mónica Fernández, Victoria Castillo, Alberto del Marcos, Maria Ángeles Villanueva, Beatriz López, Carlos Javier Rodríguez-Domínguez, Maria Galan, Juan Carlos Cantón, Rafael Lietor, Aurora Rojo, Silvia Eiros, JM: Hinojosa, Carmen Gonzalez, Isabel Torner, Nuria Banner, David Leon, Alberto Cuesta, Pablo Rowe, Thomas Kelvin, David 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 13, 6 (2009), R201 [11 pp.] Crit. care Critical care 1364-8535 1124099 http://zaguan.unizar.es/record/165403/files/texto_completo.pdf Versión publicada 2766744 http://zaguan.unizar.es/record/165403/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:165403 articulos driver 2026-01-08-14:09:55 ARTICLE