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. 2011 Aug 31:11:232.
doi: 10.1186/1471-2334-11-232.

Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza

Raquel Almansa  1 , Andres Anton, Paula Ramirez, Ignacio Martin-Loeches, David Banner, Tomás Pumarola, Luoling Xu, Jesús Blanco, Longsi Ran, Guillermo Lopez-Campos, Fernando Martin-Sanchez, Lorenzo Socias, Ana Loza, David Andaluz, Enrique Maravi, Mónica Gordón, Maria C Gallegos, Victoria Fernandez, Cristobal León, Pedro Merino, Maria Angeles Marcos, Francisco Gandía, Felipe Bobillo, Salvador Resino, Jose M Eiros, Carmen Castro, Paula Mateo, Milagros Gonzalez-Rivera, Jordi Rello, Raul Ortiz de Lejarazu, David J Kelvin, Jesus F Bermejo-Martin
Affiliations

Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza

Raquel Almansa et al. BMC Infect Dis. .

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.

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Figures

Figure 1
Figure 1
Box plot representation of pharyngeal viral load in ventilated (MV) and non ventilated patients (NMV).
Figure 2
Figure 2
Comparison of cytokine levels in plasma in ventilated (MV) and non ventilated patients (NMV) by box plots. Normalized levels against control median are showed.
Figure 3
Figure 3
Comparison of cytokine levels in plasma in ventilated (MV) and non ventilated patients (NMV) by box plots. Normalized levels against control median are showed.
Figure 4
Figure 4
Correlations between viral load and cytokines (p < 0.05) (n = 23 patients).
See this image and copyright information in PMC

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