Here we propose PPIs as effective drugs in severe sepsis or septic shock, based on the following pieces of evidence: (i) in the mouse model of acute lethal endotoxic shock, ~60% of mice treated with ESO 30 min before LPS injection undergo a complete recovery; (ii) ESO increases the survival rate even if administered after induction of shock; (iii) the systemic production of TNF-α and IL-1β is lowered in ESO-treated mice. This evidence concerns the gene TNF and Sepsis.