Cumulatively, our mouse and cotton rat data with Eritoran, a TLR4 antagonist developed for the treatment of sepsis, showed that Eritoran treatment inhibited influenza virus-induced, (i) oxidized phospholipid expression-mediated cytokine storm in vivo and in vitro, (ii) HMGB1-mediated TLR4-dependent signaling in vitro, and (iii) HMGB1 release into serum in vivo, and improved influenza-induced lethality, lung pathology, and clinical symptoms (13, 14). This evidence concerns the gene TLR4 and influenza.