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Objective: Psychosocial stress has been suggested as a possible aggravating factor in liver diseases, however, the underlying mechanism has yet to be clarified. Recently, our research revealed that electric foot-shock stress aggravated NK1.1 Ag+ T cell-dependent a-galactosylceramide (alpha-GalCer)-induced hepatitis in mice via a mechanism mediated by endogenous glucocorticoids. In this study, we examined whether or not such aggravation could be applied to a psychosocially stressful situation, e.g. social disruption stress. Methods: Male wildtype C57BL/6 (B6) or B6 hepatitis virus type B surface antigen transgenic (HBs-tg) mice, a hepatitis B virus carrier mouse model, were exposed 3 times in 1 week to social disruption stress in which an 8-month-old aggressive male intruder was placed into their home cage (5 mice per group) for 2 h. Twelve hours after the final exposure to the stress, the wild-type and HBs-tg mice were intravenously injected with alpha-GalCer. Results:The stress-exposed wild-type mice exhibited significantly reduced thymus weight loss compared with the control animals. Moreover, this stress regimen led to a significant increase in serum alanine aminotransferase levels in both the wild-type and the HBs-tg mice, although the increase in the HBs-tg mice was higher than that in the wild-type mice. Conclusion: These findings demonstrated that, similar to electric foot-shock stress, social disruption stress exacerbated alpha-GalCer-induced hepatitis. Copyright (C) 2005 S. Karger AG, Basel.

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.