During severe bacterial infections, the transcription factor NF-κB is both an asset and a liability. On page , Ye et al. show that its activation in endothelial cells single-handedly perpetuates the inflammation that drives septic shock.
NF-κB is required in endothelial cells for new blood vessels to grow. And in immune cells, its activation is essential for defense against bacteria and other infectious agents. Blocking NF-κB in mice, for example, turns a normally manageable infection deadly. But more selectively inactivating the protein has proven beneficial in other systems, including certain cancer models.
Following this lead, Ye et al. disabled NF-κB activation only in endothelial cells. The resulting mice survived a normally lethal bacterial infection and avoided septic shock. Being free of active NF-κB allowed the endothelial cells lining blood vessels to maintain their cell–cell junctions and minimize their stickiness, thus limiting the fluid leakage and massive immune cell infiltration into tissues that triggers shock.
Thus, NF-κB–driven activation of endothelial cells, not immune cells, seems to be the driving force behind the escalating inflammation that causes sepsis. 
