IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors

Neurobiol Dis. 2006 Sep;23(3):587-94. doi: 10.1016/j.nbd.2006.05.001. Epub 2006 Jul 12.


Cytokine-dependent mechanisms in the CNS have been implicated in the pathogenesis of depression. Interleukin-6 is upregulated in depressed patients and dowregulated by antidepressants. It is, however, unknown whether IL-6 is involved in the pathogenesis of depression. We subjected IL-6-deficient mice (IL-6(-/-)) to depression-related tests (learned helplessness, forced swimming, tail suspension, sucrose preference). We also investigated IL-6 in the hippocampus of stressed wild-type mice. IL-6(-/-) mice showed reduced despair in the forced swim, and tail suspension test, and enhanced hedonic behavior. Moreover, IL-6(-/-) mice exhibited resistance to helplessness. This resistance may be caused by the lack of IL-6, because stress increased IL-6 expression in wild-type hippocampi. This suggests that IL-6 is a component in molecular mechanisms in the pathogenesis of depression. IL-6(-/-) mice represent tools to study IL-6-dependent signaling pathways in the pathophysiology of depression in vivo. Moreover, these mice may support the screening of compounds for depression by altering cytokine-mediated signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety Disorders / genetics
  • Anxiety Disorders / immunology
  • Anxiety Disorders / physiopathology
  • Behavior, Animal / physiology
  • Brain Chemistry / genetics
  • Brain Chemistry / immunology
  • Depressive Disorder / genetics*
  • Depressive Disorder / immunology*
  • Depressive Disorder / physiopathology
  • Disease Models, Animal
  • Genetic Predisposition to Disease / genetics*
  • Helplessness, Learned
  • Hippocampus / immunology*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Interleukin-6 / genetics*
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Stress, Psychological / genetics*
  • Stress, Psychological / immunology*
  • Stress, Psychological / physiopathology


  • Interleukin-6