Severe influenza is often associated with disease manifestations outside the respiratory tract. While proinflammatory cytokines can be detected in the lungs and blood of infected patients, the role of extra-respiratory organs in the production of proinflammatory cytokines is unknown. Here, we show that both 2009 pandemic H1N1 influenza A (H1N1) virus and highly pathogenic avian influenza A (H5N1) virus induce expression of tumor necrosis factor α, interleukin-6, and interleukin-8 in the respiratory tract and central nervous system. In addition, H5N1 virus induced cytokines in the heart, pancreas, spleen, liver, and jejunum. Together, these data suggest that extra-respiratory tissues contribute to systemic cytokine responses, which may increase the severity of influenza.

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Keywords cytokine storm, cytokines, extra-respiratory responses, H1N1, H5N1, influenza, pathogenesis, systemic disease
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Journal The Journal of Infectious Diseases
Short, K.R, Veeris, R. (Rebecca), Leijten, L.M.E, van den Brand, J.M.A, Jong, V.L, Stittelaar, K.J, … van Riel, D.A.J. (2017). Proinflammatory Cytokine Responses in Extra-Respiratory Tissues during Severe Influenza. The Journal of Infectious Diseases, 216(7), 829–833. doi:10.1093/infdis/jix281