Cytokine responses in patients with mild or severe influenza A(H1N1)pdm09.

ABSTRACT

BACKGROUND: Influenza virus affects millions of people worldwide each year. More severe infection occurs in the elderly, very young and immunocompromised. In 2009, a new variant of swine origin (influenza A(H1N1)pdm09 virus) emerged that produced severe disease in young healthy adults. OBJECTIVES: The aim of this study was to determine whether cytokine concentrations are associated with clinical outcome in patients infected influenza A(H1N1)pdm09 virus. STUDY DESIGN: Plasma concentration of 32 cytokines and growth factors were measured using a multiplex bead immunoassay and conventional ELISA in four patient groups. Patients with severe and mild influenza A(H1N1)pdm09 virus infection, rhinovirus infection and healthy volunteers were investigated. In addition, serial samples of respiratory secretions from five patients with severe influenza A(H1N1)pdm09 virus infection were examined. RESULTS: The majority of cytokines measured were elevated in patients with viral respiratory infections compared to the healthy controls. Concentrations of IL-6, IL-10, IL-15, IP-10, IL-2R, HGF, ST2 and MIG were significantly higher (p<0.05) and EGF significantly lower (p=0.0001) in patients with severe influenza A(H1N1)pdm09 virus infection compared to those with mild influenza A(H1N1)pdm09 virus and rhinovirus infection. CONCLUSIONS: A number of cytokines were found to be substantially elevated in patients with severe influenza A(H1N1)pdm09 virus infection. This supports and extends other published work suggesting a role for proinflammatory cytokines in influenza-induced lung pathology. Interestingly, EGF was significantly lower in patients with severe infection suggesting it is actively suppressed. As EGF has a role in role in cell proliferation and tissue repair, it may protect the lung from host or virus mediated damage.