Mechanical stress-dependent secretion of interleukin 6 by endothelial cells after portal vein embolization: clinical and experimental studies.
OBJECTIVE
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-alpha (TNF-alpha), 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 3h after PVE. The concentrations of TNF-alpha 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.
Kawai
Masami
M
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Japan.
Naruse
Keiji
K
Komatsu
Shunichiro
S
Kobayashi
Satoshi
S
Nagino
Masato
M
Nimura
Yuji
Y
Sokabe
Masahiro
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D004617:Embolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008102:Liver Circulation; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011169:Portal Vein; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor