Targeting the intersection of angiopoietin-TIE2 signaling with arachidonic acid metabolism can prevent septic death

Neonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism. We here show that these two pathways appear to be functionally connected via reactive oxygen species (ROS) with a direct role of nitric oxide (NO). Targeting this intersection with oral administration of arachidonic acid and/or the NO donor L-arginine provided prophylactic as well as therapeutic protection from septic death.