Monophosphoryl lipid A alters the inflammatory response of endothelial cells challenged with lipopolysaccharide (855.4)

Abstract

Monophosphoryl lipid A (MPLA) is a lipid A mimetic that induces a state of endotoxin tolerance when given prior to lipopolysaccharide (LPS) challenge. As endothelial cells regulate inflammation, we hypothesized that MPLA would downregulate the inflammatory response of endothelial cells to LPS in a serum dependent manner. We cultured human umbilical vein endothelial cells (HUVECs) and exposed them to MPLA or a vehicle control for 6 hours. Afterwards, HUVECs were challenged with TNFα or LPS or saline for 24 hours. We assessed activation by quantifying IL‐6 levels in the culture media. In the presence of 2% serum, MPLA alone enhanced IL‐6 production compared to controls. LPS increased IL‐6 production much more potently, but this effect was reduced by 47 ± 5% when pre‐exposed to MPLA (p<0.05). MPLA had no effect on TNFα‐induced IL‐6 production. In the absence of serum, LPS induction of IL‐6 was nearly abolished secondary to lack of serum co‐factors. However, MPLA enhancement of IL‐6 production persisted in a serum free environment (p<0.05). These studies demonstrate that MPLA alters the inflammatory response of endothelial cells after LPS challenge and that the effects of MPLA are serum independent.