Social disruption stress exacerbates alpha-galactosylceramide-induced hepatitis in mice

Neuroimmunomodulation. 2005;12(6):375-9. doi: 10.1159/000091131.


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 alpha-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 wild-type 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Chemical and Drug Induced Liver Injury / immunology
  • Chemical and Drug Induced Liver Injury / physiopathology*
  • Flow Cytometry
  • Galactosylceramides / toxicity*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Stress, Psychological / immunology
  • Stress, Psychological / physiopathology*
  • Thymus Gland / pathology


  • Galactosylceramides
  • alpha-galactosylceramide
  • Alanine Transaminase