Mechanical stress-dependent secretion of interleukin 6 by endothelial cells after portal vein embolization: clinical and experimental studies

Background/Aims: Interleukin-6 (IL-6) is an essential early signal in liver regeneration, however, little is known about what triggers IL-6 release. Changes in portal hemodynamics after portal vein embolization (PVE) may contribute to IL-6 release, leading to regeneration of non-embolized lobe. Methods: In 22 patients who underwent right PVE, the diameters of the left portal branches, liver volumes, and serum concentrations of IL-6, tumor necrosis factor-α (TNF-α), and hepatocyte growth factor (HGF) were measured. We then studied endothelial cells cultured on an elastic silicone membrane and subjected to continuous uni-axial stretch. Supernatant cytokine concentrations were measured. Results: The diameters of the portal branches increased by 150% after PVE. Serum IL-6 concentrations increased within 3 h after PVE. The concentrations of TNF-α and HGF remained unchanged. The left lobe volume increased 2 weeks after PVE. The IL-6 concentrations in the supernatant of endothelial cells with stretch stress were higher than that in the non-stretched control group. Conclusions: These findings indicate that PVE dilates the portal branches in the non-embolized lobe, exposing hepatic vasculature to stretch stress. This hemodynamic change may act as a trigger for IL-6 release from endothelial cells and contribute to the activation of regenerative cascade in the non-embolized lobes.