title: Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza.
abstract: BACKGROUND
  Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients.
  
  
  METHODS
  Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient.
  
  
  RESULTS
  Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus.
  
  
  CONCLUSIONS
  Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.
authors: Infection & Immunity Medical Investigation Unit (IMI), Hospital Clínico Universitario-IECSCYL, Avda Ramón, y Cajal 3, 47005 Valladolid, Spain.
authors: Raquel
authors: R
authors: Almansa
authors: Andres
authors: A
authors: Anton
authors: Paula
authors: P
authors: Ramirez
authors: Ignacio
authors: I
authors: Martin-Loeches
authors: David
authors: D
authors: Banner
authors: Tomás
authors: T
authors: Pumarola
authors: Luoling
authors: L
authors: Xu
authors: Jesús
authors: J
authors: Blanco
authors: Longsi
authors: L
authors: Ran
authors: Guillermo
authors: G
authors: Lopez-Campos
authors: Fernando
authors: F
authors: Martin-Sanchez
authors: Lorenzo
authors: L
authors: Socias
authors: Ana
authors: A
authors: Loza
authors: David
authors: D
authors: Andaluz
authors: Enrique
authors: E
authors: Maravi
authors: Mónica
authors: M
authors: Gordón
authors: Maria C
authors: MC
authors: Gallegos
authors: Victoria
authors: V
authors: Fernandez
authors: Cristobal
authors: C
authors: León
authors: Pedro
authors: P
authors: Merino
authors: Maria Angeles
authors: MA
authors: Marcos
authors: Francisco
authors: F
authors: Gandía
authors: Felipe
authors: F
authors: Bobillo
authors: Salvador
authors: S
authors: Resino
authors: Jose M
authors: JM
authors: Eiros
authors: Carmen
authors: C
authors: Castro
authors: Paula
authors: P
authors: Mateo
authors: Milagros
authors: M
authors: Gonzalez-Rivera
authors: Jordi
authors: J
authors: Rello
authors: Raul Ortiz
authors: RO
authors: de Lejarazu
authors: David J
authors: DJ
authors: Kelvin
authors: Jesus F
authors: JF
authors: Bermejo-Martin
mesh_terms: D000328:Adult; D016638:Critical Illness; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000302:isolation & purification*; D007251:Influenza, Human / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000821:virology*; D016133:Polymerase Chain Reaction / Q000379:methods; D019562:Viral Load / Q000379:methods
chemical_list: D016207:Cytokines