Our initial finding that TLR4−/− mice are highly refractory to lethal influenza infection (13, 14) led to the hypothesis that TLR4 antagonist therapy would mitigate disease by blunting the “cytokine storm.” Eritoran (Eisai, Inc.), a potent lipid A analog antagonist that acts by competitive inhibition of the TLR4 co-receptor, MD-2 (14), failed in Phase 3 clinical trials for all-cause sepsis (15). This evidence concerns the gene TLR4 and influenza.