Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 35, Issue 3, Pages 664-675Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2010.06.014
Keywords
Cytokines; Depression; IDO; Inflammation; T cell activation; Tryptophan
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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-alpha (TNF alpha). The same meta-analysis found that plasma IL-2 and interferon-(IFN)gamma 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 IFN gamma; 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-alpha (IFN alpha)-based immunotherapy shows that baseline and IFN alpha-induced activation of T cells, IDO activity and TRYCAT formation are related to the development of IFN alpha-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 IFN gamma production. This review shows that inflammation and cell-mediated immune activation are key factors in depression. (C) 2010 Elsevier Inc. All rights reserved.
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