Breaking Barriers: Characterization of the Intradermal Lipopolysaccharide Challenge as an In Vivo Model for Controlled Induction of Vascular Leakage in Healthy Volunteers.

Vascular leakage and its associated phenomena vasodilation and endothelial activation are pathophysiological features of various diseases. Multiple drug candidates targeting these phenomena are in development, necessitating translational models to demonstrate proof-of-pharmacology and proof-of-mechanism in early-phase clinical trials. This single-center experimental study evaluated the intradermal lipopolysaccharide (id LPS) challenge model as a tool to induce and characterize vascular leakage in healthy participants. Eight participants (male:female = 4:4) received id LPS in the volar forearms, followed by serial pharmacodynamic assessments, including imaging and suction blister induction up to 9 hours after injection. Id LPS administration resulted in significant increases in skin perfusion (P