Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza
| Autor: | Pablo Cuesta, Alberto del Castillo, Thomas Rowe, Raquel Almansa, José María Eiros, Paula Ramirez, Silvia Rojo, Alberto Tenorio-Abreu, Isabel Gonzalez, Mario Rodríguez-Domínguez, José Manuel Gómez, Carlos J.Lopez, Ignacio Martin-Loeches, Maria C Gallegos, Raúl Ortiz de Lejarazu, Juan Carlos Galán, Aurora Lietor, Elia Sanchez, Rafael Cantón, Jordi Rello, Monica Gordon, David Banner, Carmen Hinojosa, Maria J. Ramos, David Varillas, Victoria Fernández, David J. Kelvin, S Huidobro, M. Lourdes Molina, Nuria Torner, Alberto J. Leon, Jesus F. Bermejo-Martin, M. A. Marcos, Beatriz Villanueva, Carlos Serón, Tomás Pumarola, Dariela Micheloud |
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| Přispěvatelé: | [Bermejo-Martin,JF, Ortiz de Lejarazu,R, Almansa,R, Varillas,D, Rojo,S, Eiros,JM] National Centre of Influenza, Hospital Clínico Universitario de Valladolid, Valladolid, Spain. [Bermejo-Martin,JF, Eiros,JM] Unidad de Investigación en Infección e Inmunidad- Microbiology Service, Hospital Clínico Universitario de Valladolid- IECSCYL, Valladolid, Spain. [Pumarola,T, Marcos,MA] Virology Laboratory, Hospital Clinic de Barcelona, Barcelona. [Rello,J, Martin-Loeches,I] Critical Care Department, Joan XXIII University Hospital-CIBERes Enfermedades Respiratorias-IISPV. Tarragona, Spain. [Ramírez,P, Gordón,M] Critical Care Department, Hospital Universitario La Fe, Spain. [Gallegos,MC, Fernández,V] Microbiology Service, Hospital Son Llatzer, Palma de Mallorca, Spain. [Serón,C] Intensive Care Unit, Hospital General San Jorge, Huesca, Spain. [Micheloud,D, Gomez,JM] Intensive Care Unit & Internal Medicine Service, Hospital Gregorio Marañón, Madrid, Spain. [Tenorio-Abreu,A, Ramos,MJ] Microbiology Service, Hospital Universitario de Canarias, Santa Cruz De Tenerifey, Spain. [Molina,ML] Microbiology Service, Hospital General de La Palma, Breña Alta, Spain. [Huidobro,S] Intensive Care Unit, Hospital Universitario de Canarias, Santa Cruz De Tenerifeý, Spain. [Sanchez,E] Intensive Care Unit, Hospital Virgen del Rocío, Sevilla, Spain. [Del Castillo,A] Intensive Care Unit Service, Hospital Son Llatzer, Palma de Mallorca, Spain. [Villanueva,V, López,CJ] Intensive Care Unit Service, Hospital Lozano Blesa, Zaragoza, Spain. [Rodríguez-Domínguez,M, Galan,JC, Cantón,R] Microbiology Service, Hospital Universitario Ramón y Cajal & CIBERESP, Madrid, Spain. [Lietor,A] Intensive Care Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain. [Hinojosa,C, Gonzalez,I] Infectious Diseases Service, Hospital Clínico Universitario, Valladolid, Spain. [Torner,N] Preventive Medicine Service, Hospital Universitario Valle Hebron & CIBERESP, Barcelona, Spain. [Banner,D, Rowe,T, Kelvin,DJ] Experimental Theraputics Division, University Health Network, Medical Discovery Tower, Toronto,Canada. [Leon,A, Kelvin,DJ] International Institute of Infection and Immunity, Shantou University, Shantou, Guangdong Province, PR China. [Cuesta,P] Intensive Care Unit, Hospital de Villarobredo, Villarrobledo, Spain. [Rowe,T, Kelvin,DJ] Department of Immunology, University of Toronto, Medical Discovery Tower, Toronto, Canada., This work was possible thanks to the financial support obtained from the Ministry of Science of Spain and Consejería de Sanidad Junta de Castilla y León, Programa de Investigación comisionada en gripe, GR09/0021, Programa para favorecer la incorporación de grupos de investigación en las Instituciones del Sistema Nacional de Salud, EMER07/050, and Proyectos en Investigación Sanitaria, PI081236. CIHR, NIH and LKSF-Canada support DJK. |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
viruses
humanos Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Nucleotides::Polynucleotides::Oligonucleotides::Oligodeoxyribonucleotides::DNA Primers [Medical Subject Headings] Host response Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] quimiocinas Critical Care and Intensive Care Medicine medicine.disease_cause Severity of Illness Index virus de la influenza A células TH1 Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] 0302 clinical medicine Quimiocinas Mediana Edad Carga Viral Interferon duración de estancia hospitalaria Analytical Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Hospitalization::Length of Stay [Medical Subject Headings] Influenza A virus pruebas de inhibición de la hemaglutinación Masculino mediana edad Células TH1 0303 health sciences Adulto Femenino virus diseases Citocinas Viral Load Middle Aged adulto 3. Good health Humanos Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes Mononuclear::Lymphocytes::Lymphocyte Subsets::T-Lymphocyte Subsets::T-Lymphocytes Helper-Inducer::Th1 Cells [Medical Subject Headings] ARN Intensive Care Units Cytokines carga viral Chemokines Analytical Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Immunologic Tests::Serologic Tests::Hemagglutination Inhibition Tests [Medical Subject Headings] Viral load medicine.drug Adult Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Methods::Research Design::Patient Selection [Medical Subject Headings] Índice de Severidad de la Enfermedad unidades de cuidados intensivos Check Tags::Male [Medical Subject Headings] Cartilla de ADN selección de los pacientes Health Care::Health Care Facilities Manpower and Services::Health Facilities::Hospital Units::Intensive Care Units [Medical Subject Headings] Virus 03 medical and health sciences Pruebas de Inhibición de Hemaglutinación Immune system Organisms::Viruses::RNA Viruses::Orthomyxoviridae::Influenzavirus A::Influenza A virus::Influenza A Virus H1N1 Subtype [Medical Subject Headings] medicine Subtipo H1N1 del Virus de la Influenza A Gripe Humana Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] Humans Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Nucleic Acids::RNA::RNA Viral [Medical Subject Headings] índice de gravedad de la enfermedad Unidades de Cuidados Intensivos 030304 developmental biology DNA Primers Chemicals and Drugs::Amino Acids Peptides and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines [Medical Subject Headings] Host (biology) business.industry Research Patient Selection Selección de Paciente Pandemic influenza Chemicals and Drugs::Amino Acids Peptides and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Chemokines [Medical Subject Headings] biochemical phenomena metabolism and nutrition Length of Stay Hemagglutination Inhibition Tests Th1 Cells Virology Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Health Status Indicators::Severity of Illness Index [Medical Subject Headings] cebadores de ADN Check Tags::Female [Medical Subject Headings] Analytical Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings] Immunology citocinas RNA business ARN Viral Diseases::Virus Diseases::RNA Virus Infections::Orthomyxoviridae Infections::Influenza Human [Medical Subject Headings] 030215 immunology Tiempo de Internación |
| Zdroj: | Critical Care CRITICAL CARE r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe instname |
| ISSN: | 1364-8535 |
| Popis: | 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. This work has been made by an international team pertaining to the Spanish-Canadian Consortium for the Study of Influenza Immunopathogenesis. The authors would like to thank Lucia Rico and Veronica Iglesias for their assistance in the technical development of the multiplex cytokine assays, to Bego a Nogueira for her technical support, and to Nikki Kelvin for language revision of this article. This work was possible thanks to the financial support obtained from the Ministry of Science of Spain and Consejeria de Sanidad Junta de Castilla y Leon, Programa de investigacion comisionada en gripe, GR09/0021, Programa para favorecer la incorporacion de grupos de investigacion en las Instituciones del Sistema Nacional de Salud, EMER07/050, and Proyectos en Investigacion Sanitaria, PI081236. CIHR, NIH and LKSF-Canada support DJK. This sponsorship made possible reagent acquisition and sample transportation between participant groups. |
| Databáze: | OpenAIRE |
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