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

Chida, Y; Sudo, N; Motomura, Y; Kubo, C; (2004) Electric foot-shock stress drives TNF-alpha production in the liver of IL-6-deficient mice. NEUROIMMUNOMODULAT , 11 (6) 419 - 424. 10.1159/000080153. Green open access


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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-alpha (TNF-alpha). 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-alpha 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-alpha level after stress in parallel with serum TNF-alpha elevation, whereas no such TNF-alpha 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-alpha production in the liver, thereby decreasing the blood TNF-alpha level. In contrast, IL-6 secretion was shown to have no protective effect on stress-triggered liver injury. Copyright (C) 2004 S. Karger AG, Basel.

Type: Article
Title: Electric foot-shock stress drives TNF-alpha production in the liver of IL-6-deficient mice
Open access status: An open access version is available from UCL Discovery
DOI: 10.1159/000080153
Keywords: anti-inflammatory effect, apoptosis, electric foot-shock, IL-6, liver injury, psychoneuroimmunology, psychophysical stress, TNF-alpha, PLASMA INTERLEUKIN-6, IMMOBILIZATION STRESS, IL-6, CELLS, RATS, EXPRESSION, INDUCTION, INJECTION, ENDOTOXIN, PATHWAYS
UCL classification: UCL
URI: https://discovery.ucl.ac.uk/id/eprint/2921
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