It is well known that the recognition receptor "RAGE" and HMGB-1 play a central role in the innate immune system with an impact on its perpetuation and amplification [22] . RAGE stimulation results in sustained NF-B activation, which may be a predictor of severity in sepsis [32] . Conditions that induce NF-B also increase RAGE expression, which in turn produces sustained inflammation; this is seen in CAP, where RAGE ligands are abundantly present. Angus et al. found that CAP patients had higher HMGB-1 concentrations, and this correlated with mortality [19] . Gaini et al. also found higher levels of HMGB-1 in CAP [33] . Studies of severe influenza CAP demonstrated an association between excessive release of cytokines and increased mortality [34, 35] . However, Alleva et al. found in a murine model of severe influenza that HMGB-1 concentrations were not increased in plasma at the time of peak mortality, and peak levels of HMGB1 did not occur until relatively late in infection [36] .