TY - JOUR
T1 - Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza
AU - Almansa, Raquel
AU - Anton, Andres
AU - Ramirez, Paula
AU - Martin-Loeches, Ignacio
AU - Banner, David
AU - Pumarola, Tomás
AU - Xu, Luoling
AU - Blanco, Jesús
AU - Ran, Longsi
AU - Lopez-Campos, Guillermo
AU - Martin-Sanchez, Fernando
AU - Socias, Lorenzo
AU - Loza, Ana
AU - Andaluz, David
AU - Maravi, Enrique
AU - Gordón, Mónica
AU - Gallegos, Maria C.
AU - Fernandez, Victoria
AU - León, Cristobal
AU - Merino, Pedro
AU - Marcos, Maria T.
AU - Gandía, Francisco
AU - Bobillo, Felipe
AU - Resino, Salvador
AU - Eiros, Jose M.
AU - Castro, Carmen
AU - Mateo, Paula
AU - Gonzalez-Rivera, Milagros
AU - Rello, Jordi
AU - de Lejarazu, Raul O.
AU - Kelvin, David J.
AU - Bermejo-Martin, Jesus F.
PY - 2011/8/31
Y1 - 2011/8/31
N2 - 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.
AB - 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.
KW - Critical
KW - Cytokines
KW - Influenza
KW - Patients
KW - Virus
UR - http://www.scopus.com/inward/record.url?scp=80052158225&partnerID=8YFLogxK
U2 - 10.1186/1471-2334-11-232
DO - 10.1186/1471-2334-11-232
M3 - Article
C2 - 21880131
AN - SCOPUS:80052158225
VL - 11
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
SN - 1471-2334
M1 - 232
ER -