Analysis from the laboratories led by my colleagues Paul Thomas at St Jude, Katherine Kedzierska in Melbourne, and our collaborator Janqing Xu in Shanghai is illuminating the cytokine/chemokine response profiles for human adult and pediatric populations with naturally acquired influenza, and in mice and ferrets exposed to these viruses under controlled conditions. Particularly informative is the Shanghai cohort of very severe H7N9 pneumonia cases, where the protective effect of the IFITM3 gen is very obvious. The cytokine/chemokine patterns are dramatic and reproducible for patients from all geographic regions, and are comparable in character for the spectrum of different molecules identified in nasal wash (human) and bronchoalveolar lavage (mice/ferrets) samples by cytokine bead assays. The prominent players are innate in character and their levels of production are generally correlated with the severity of inflammation. This is particularly clear following treatment with the antiviral drug Tamiflu, which acts by inhibiting the release of mature virus particles from the cell membrane, leading to a less severe inflammatory response without any reduction in virus titers. Both the protective roles of these responses, and the possible exacerbating effect of cytokine shock in severe influenza, will be discussed.