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Clinical aspects and cytokine response in severe H1N1 influenza A virus infection

Natalia Hagau1*, Adriana Slavcovici2, Daniel N Gonganau1, Simona Oltean2, Dan S Dirzu1, Erika S Brezoszki1, Mihaela Maxim1, Constantin Ciuce1, Monica Mlesnite1, Rodica L Gavrus1, Carmen Laslo1, Radu Hagau3, Magda Petrescu1 and Daniela M Studnicska1

Author Affiliations

1 University Emergency County Hospital of Cluj, Clinicilor 3-5, 400006 Cluj-Napoca, Romania

2 Teaching Hospital of Infectious Disease Cluj-Napoca, Iuliu Moldovan 23, 400348 Cluj-Napoca, Romania

3 Memorial Hospital of Rhode Island, Brown University, 111 Brewster Street, Pawtucket, RI 02860, USA

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Critical Care 2010, 14:R203  doi:10.1186/cc9324

Published: 9 November 2010



The immune responses in patients with novel A(H1N1) virus infection (nvA(H1N1)) are incompletely characterized. We investigated the profile of Th1 and Th17 mediators and interferon-inducible protein-10 (IP-10) in groups with severe and mild nvA(H1N1) disease and correlated them with clinical aspects.


Thirty-two patients hospitalized with confirmed nvA(H1N1) infection were enrolled in the study: 21 patients with nvA(H1N1)-acute respiratory distress syndrome (ARDS) and 11 patients with mild disease. One group of 20 patients with bacterial sepsis-ARDS and another group of 15 healthy volunteers were added to compare their cytokine levels with pandemic influenza groups. In the nvA(H1N1)-ARDS group, the serum cytokine samples were obtained on admission and 3 days later. The clinical aspects were recorded prospectively.


In the nvA(H1N1)-ARDS group, obesity and lymphocytopenia were more common and IP-10, interleukin (IL)-12, IL-15, tumor necrosis factor (TNF)α, IL-6, IL-8 and IL-9 were significantly increased versus control. When comparing mild with severe nvA(H1N1) groups, IL-6, IL-8, IL-15 and TNFα were significantly higher in the severe group. In nonsurvivors versus survivors, IL-6 and IL-15 were increased on admission and remained higher 3 days later. A positive correlation of IL-6, IL-8 and IL-15 levels with C-reactive protein and with > 5-day interval between symptom onset and admission, and a negative correlation with the PaO2:FiO2 ratio, were found in nvA(H1N1) groups. In obese patients with influenza disease, a significant increased level of IL-8 was found. When comparing viral ARDS with bacterial ARDS, the level of IL-8, IL-17 and TNFα was significantly higher in bacterial ARDS and IL-12 was increased only in viral ARDS.


In our critically ill patients with novel influenza A(H1N1) virus infection, the hallmarks of the severity of disease were IL-6, IL-15, IL-8 and TNFα. These cytokines, except TNFα, had a positive correlation with the admission delay and C-reactive protein, and a negative correlation with the PaO2:FiO2 ratio. Obese patients with nvA(H1N1) disease have a significant level of IL-8. There are significant differences in the level of cytokines when comparing viral ARDS with bacterial ARDS.