Direct stimulation of the vagus nerve has been shown to exert potent inflammation-reducing activities in the body (89) . Transcutaneous stimulation of the vagus nerve improves survival in mice with sepsis by reducing serum levels of HMGB1 (90) . Thus there is a distinct possibility that vagus nerve stimulation by acupuncture could control immune-mediated pathology, by limiting release of pro-inflammatory cytokines. The potential for using acupuncture in this way was recently reviewed (91) with the authors noting that 'the use of acupuncture as an adjunct therapy to conventional medical treatment for a number of chronic inflammatory and autoimmune diseases seems plausible and should be validated by confirming its cholinergicity'. Thus stimulation of the vagus nerve in patients with influenza could also represent an adjunct treatment in the management of severe influenza cases, provided it can be further investigated. Figure 2 . Potential mitigation of the action of HMGB1 and other pro-inflammatory cytokines by traditional Chinese medicines, a natural agent, and pharmaceutical drugs. The Chinese medicine glycyrrhizin, from liquorice root, binds to HMGB1 and inactivates its biological activities (34) , while the Chinese herbs A. sinensis and S. miltiorrhiza reduce the release of HMGB1 (37, 46) . Release of pro-inflammatory cytokines is reduced via inhibition of NF-kB activation, by glycyrrhizin (101-103), A. sinensis (104, 105) , and S. miltiorrhiza (106, 107) ; by the natural agent biochanin A (65, 108, 109) ; and the pharmaceutical drugs statins (110, 111) and fibrates (21, 112, 113) . Pro-inflammatory cytokine release is reduced by activation of PPARs (21) and conversely, anti-inflammatory cytokine release is increased by their activation (114, 115) . PPAR alpha is activated by fibrates (21); PPAR alpha and gamma are activated by biochanin A (64); and statins upregulate PPAR alpha and gamma and show molecular signaling properties similar to fibrates (116).