TY - JOUR ID - discovery2921 AV - public SP - 419 Y1 - 2004/// IS - 6 TI - Electric foot-shock stress drives TNF-alpha production in the liver of IL-6-deficient mice A1 - Chida, Y A1 - Sudo, N A1 - Motomura, Y A1 - Kubo, C EP - 424 VL - 11 UR - https://discovery.ucl.ac.uk/id/eprint/2921/ JF - NEUROIMMUNOMODULAT PB - KARGER KW - anti-inflammatory effect KW - apoptosis KW - electric foot-shock KW - IL-6 KW - liver injury KW - psychoneuroimmunology KW - psychophysical stress KW - TNF-alpha KW - PLASMA INTERLEUKIN-6 KW - IMMOBILIZATION STRESS KW - IL-6 KW - CELLS KW - RATS KW - EXPRESSION KW - INDUCTION KW - INJECTION KW - ENDOTOXIN KW - PATHWAYS N2 - 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. SN - 1021-7401 ER -