Bermejo-Martin, Jesus FOrtiz de Lejarazu, RaulPumarola, TomasRello, JordiAlmansa, RaquelRamírez, PaulaMartin-Loeches, IgnacioVarillas, DavidGallegos, Maria CSerón, CarlosMicheloud, DarielaGomez, Jose ManuelTenorio-Abreu, AlbertoRamos, María JMolina, M LourdesHuidobro, SamanthaSanchez, EliaGordón, MónicaFernández, VictoriaDel Castillo, AlbertoMarcos, Ma AngelesVillanueva, BeatrizLópez, Carlos JavierRodríguez-Domínguez, MarioGalan, Juan-CarlosCantón, RafaelLietor, AuroraRojo, SilviaEiros, Jose MHinojosa, CarmenGonzalez, IsabelTorner, NuriaBanner, DavidLeon, AlbertoCuesta, PabloRowe, ThomasKelvin, David J2014-07-022014-07-022009-12-11Bermejo-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):R2011364-8535http://hdl.handle.net/10668/1670Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't;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-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. 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.enQuimiocinasCitocinasCartilla de ADNFemeninoPruebas de Inhibición de HemaglutinaciónHumanosSubtipo H1N1 del Virus de la Influenza AGripe HumanaUnidades de Cuidados IntensivosTiempo de InternaciónMasculinoMediana EdadSelección de PacienteARN ViralÍndice de Severidad de la EnfermedadCélulas TH1Carga ViralAdultoMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::ChemokinesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::CytokinesMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleotides::Polynucleotides::Oligonucleotides::Oligodeoxyribonucleotides::DNA PrimersMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Immunologic Tests::Serologic Tests::Hemagglutination Inhibition TestsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Organisms::Viruses::RNA Viruses::Orthomyxoviridae::Influenzavirus A::Influenza A virus::Influenza A Virus, H1N1 SubtypeMedical Subject Headings::Diseases::Virus Diseases::RNA Virus Infections::Orthomyxoviridae Infections::Influenza, HumanMedical Subject Headings::Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospital Units::Intensive Care UnitsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Hospitalization::Length of StayMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Methods::Research Design::Patient SelectionMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, ViralMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Health Status Indicators::Severity of Illness IndexMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocyte Subsets::T-Lymphocyte Subsets::T-Lymphocytes, Helper-Inducer::Th1 CellsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral LoadMedical Subject Headings::Named Groups::Persons::Age Groups::Adultresearch article20003352open access10.1186/cc82081466-609XPMC2811892