Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression

Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):664-75. doi: 10.1016/j.pnpbp.2010.06.014. Epub 2010 Jun 20.


The first findings that depression is characterized by cell-mediated immune activation and inflammation were published between 1990-1993 (Maes et al.). Recently, it was reported that--based on meta-analysis results--depression is an inflammatory disorder because the plasma levels of two cytokines are increased, i.e. interleukin-(IL)-6 and tumor necrosis factor-α (TNFα). The same meta-analysis found that plasma IL-2 and interferon-(IFN)γ levels are not altered in depression, suggesting that there is no T cell activation in that illness. The present paper reviews the body of evidence that depression is accompanied by cell-mediated immune activation. The findings include: increased serum levels of the soluble IL-2 receptor (sIL-2R) and the sCD8 molecule; increased numbers and percentages of T cells bearing T cell activation markers, such as CD2+CD25+, CD3+CD25+, and HLA-DR+; increased stimulated production of IFNγ; higher neopterin and sTNFR-1 or sTNFR-2 levels; induction of indoleamine 2,3-dioxygenase (IDO) with lowered levels of plasma tryptophan and increased levels of tryptophan catabolites along the IDO pathway (TRYCATs); and glucocorticoid resistance in immune cells. Interferon-α (IFNα)-based immunotherapy shows that baseline and IFNα-induced activation of T cells, IDO activity and TRYCAT formation are related to the development of IFNα-induced depressive symptoms. Animal models of depression show that a cell-mediated immune response is related to the development of depression-like behavior. Antidepressants and mood stabilizers suppress different aspects of cell-mediated immunity and rather specifically target IFNγ production. This review shows that inflammation and cell-mediated immune activation are key factors in depression.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / immunology
  • Antidepressive Agents / therapeutic use
  • Depression / drug therapy
  • Depression / immunology*
  • Depression / physiopathology
  • Female
  • Humans
  • Immunity, Cellular / drug effects*
  • Immunity, Cellular / immunology
  • Immunity, Cellular / physiology
  • Immunosuppressive Agents / therapeutic use
  • Inflammation / drug therapy
  • Inflammation / physiopathology*
  • Male
  • Mental Disorders / drug therapy
  • Mental Disorders / immunology*
  • Meta-Analysis as Topic


  • Antidepressive Agents
  • Immunosuppressive Agents