Effects of inflammatory cytokines on the recurrence of liver cancer after an apparently curative operation

J Dig Dis. 2007 Aug;8(3):154-9. doi: 10.1111/j.1443-9573.2007.00292.x.


Objective: To investigate the effects of inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and vascular cell adhesion molecule (VCAM-1), on the recurrence of liver cancer after apparently curative surgical resection of the tumor.

Methods: An experimental mouse model of liver cancer metastasis was designed using hepatoma 22(H(22)) inoculated into the subserous layer of spleen of 615 mice. Partial hepatectomy (PH) or sham operation (SH) was performed at various periods of spleen inoculation and metastasic effects were recorded. The expression of inflammatory cytokines as TNF-alpha, IL-1beta, IL-6 and VCAM-1 were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR).

Results: Compared with SH, a significant augmented metastatic effect was observed in the mice with PH (P < 0.01), and higher mRNA expressions of TNF-alpha, IL-1beta, IL-6 and VCAM-1 were also observed. The peak expressions of IL-1beta, IL-6 and VCAM-1 were found at 48 and 72 h, respectively. Among them, TNF-alpha expression was found immediately increasing after 4 h and kept at a high level till 96 h after PH. The expression of VCAM-1 was found to have two peaks at 4 and 72 h after PH, 3-6 times higher than its level prior to the operation. The expression of TNF-alpha, IL-1beta, IL-6 and VCAM-1 showed a significantly positive correlation with the augmenting effect of liver metastasis in the mice model.

Conclusion: The results indicate that pro-inflammatory cytokines, TNF-alpha, IL-1beta, IL-6 and VCAM-1 might be involved in promoting the enhanced metastasis of liver cancer after surgical operation, especially the PH.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / secondary
  • Cytokines / physiology*
  • Disease Models, Animal
  • Female
  • Hepatectomy
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Mice
  • Neoplasm Recurrence, Local / immunology*
  • Splenic Neoplasms / immunology*
  • Splenic Neoplasms / secondary


  • Cytokines