Cytokine production by spleen cells after social defeat in mice: activation of T cells and reduced inhibition by glucocorticoids

Stress. 2004 Mar;7(1):55-61. doi: 10.1080/1025389042000208150.


Social disruption (SDR) is an effective model of social stress associated with an enhanced inflammatory reactivity of the immune system. The aim of the present study was to further describe SDR effects on cytokine production by spleen cells, testing selectively monocyte and T cell functions as a result of this stressor. For this purpose, splenocytes from control mice (C) and mice socially stressed for 7 days (SDR) were cultured in the presence of lipopolysaccharide (LPS) or concanavalin A (Con A). Splenocyte proliferation, cytokine production and sensitivity of spleen cells to corticosterone were assessed in vitro. The humoral response to keyhole limpet hemocyanin (KLH) immunization was assessed. SDR induced splenomegaly and enhanced splenocyte basal proliferation. The pro-inflammatory influence of SDR was confirmed by an increased release of interleukin-6 (IL-6) by LPS-stimulated cultures and by a reduced sensitivity of spleen cells to the anti-inflammatory effect of corticosterone. The mechanism increasing cytokine production in response to LPS was cytokine specific, since among inflammatory cytokines, IL-6 but not interferon-gamma (IFN-gamma) was enhanced by stress. In stressed mice, the increase in IL-6 and IFN-gamma and the decrease in IL-10 release in Con A-stimulated cultures indicate that SDR did not modify the Th1/Th2 cytokine balance but globally activated T cells. Plasma anti-KLH antibody levels were similar in both groups. Wounded and non-wounded mice presented similar responses to stress. This study shows that social disruption stress enhances the reactivity of cells from both the acquired and innate immune systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Corticosterone / blood
  • Corticosterone / pharmacology
  • Dominance-Subordination*
  • In Vitro Techniques
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism*
  • Interleukin-6 / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Organ Size
  • Spleen / cytology
  • Splenomegaly / immunology
  • Splenomegaly / pathology
  • Stress, Psychological / immunology*
  • Stress, Psychological / pathology
  • T-Lymphocytes / metabolism*


  • Interleukin-6
  • Interleukin-10
  • Interferon-gamma
  • Corticosterone