Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression.
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.
Maes
Michael
M
Maes Clinics@TRIA, 998 Rimklongsamsen Road, Piyavate Hospital, Bangkok 10310, Thailand. miermeat@yahoo.com
D000928:Antidepressive Agents / Q000276:immunology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy / Q000276:immunology*; D015201:Meta-Analysis as Topic
D000928:Antidepressive Agents; D007166:Immunosuppressive Agents