Electric foot-shock stress drives TNF-α production in the liver of IL-6-deficient mice

Yoichi Chida, Nobuyuki Sudo, Yoshitomo Motomura, Chiharu Kubo

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22 Citations (Scopus)


Objectives: Accumulating evidence has shown that interleukin-6 (IL-6) has pleiotropic effects on a variety of biological functions, including its antiapoptotic potential during liver injury. Our previous work demonstrated that restraint stress-induced elevation of plasma IL-6 negatively regulates plasma tumor necrosis factor-α (TNF-α). Herein, we further clarified the mechanism underlying the above finding and investigated the effect of IL-6 on liver apoptosis triggered by stress. Methods: Male C57BL/6J and IL-6-deficient C57BL/SV129 mice were exposed to 1 h of electric foot-shock stress. Thereafter, the serum, liver and spleen TNF-α levels were measured at several time points. Serum alanine aminotransferase (ALT), liver caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) activities were analyzed to evaluate the severity of liver injury and apoptosis. Results: The liver, but not the spleen, of the IL-6-deficient mice exhibited a significant increase in TNF-α level after stress in parallel with serum TNF-α elevation, whereas no such TNF-α responses were found in the wild animals. No significant differences in stress-induced elevation of serum ALT levels, liver caspase-3 activities and the number of TUNEL-positive hepatocytes were found between the wild and IL-6-deficient mice. Conclusions: Taken together, these results indicate that IL-6 may play a critical role in suppressing TNF-α production in the liver, thereby decreasing the blood TNF-α level. In contrast, IL-6 secretion was shown to have no protective effect on stress-triggered liver injury.

Original languageEnglish
Pages (from-to)419-424
Number of pages6
Issue number6
Publication statusPublished - 2004

All Science Journal Classification (ASJC) codes

  • Immunology
  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems


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