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Increased IL-6 trans-signaling in depression: focus on the tryptophan catabolite pathway, melatonin and neuroprogression

Anderson, George, Kubera, Marta, Duda, Weronika, Lasoń, Władysław, Berk, Michael and Maes, Michael 2013, Increased IL-6 trans-signaling in depression: focus on the tryptophan catabolite pathway, melatonin and neuroprogression, Pharmacological reports, vol. 65, no. 6, pp. 1647-1654, doi: 10.1016/S1734-1140(13)71526-3.

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Title Increased IL-6 trans-signaling in depression: focus on the tryptophan catabolite pathway, melatonin and neuroprogression
Author(s) Anderson, George
Kubera, Marta
Duda, Weronika
Lasoń, Władysław
Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Maes, Michael
Journal name Pharmacological reports
Volume number 65
Issue number 6
Start page 1647
End page 1654
Total pages 8
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2013-11
ISSN 1734-1140
Keyword(s) Animals
Depression
Humans
Inflammation
Interleukin-6
Receptors, Interleukin-6
Signal Transduction
Tryptophan
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
indoleamine 2,3-dioxygenase
cytokines
melatonin
oxidative stress
neuroprogression
PROTEIN-KINASE
CELLS
DISORDERS
RECEPTOR
BRAIN
PHOSPHORYLATION
NEUROGENESIS
CONTRIBUTES
ASTROCYTES
Summary Depression has been conceptualized as a disorder driven by immuno-inflammatory pathways and oxidative and nitrosative stress. These factors couple to the induction of neuroregulatory tryptophan catabolites via the activation of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Oxidative damage to neoepitopes increases autoimmune responses, changing the nature of the neural substrate of recurrent depression, which leads to neuroprogression and drives treatment resistance. A number of pro-inflammatory cytokines are linked to these processes. Here, we focus on the role of interleukin (IL)-6 in depression and its associated disorders; we highlight the progress made since the first paper showing increased IL-6 levels was published 20 years ago by Maes and colleagues. When coupled with increased levels of the soluble IL-6 receptor in depression, higher levels of IL-6 may indicate increased IL-6 trans-signaling, whereby IL-6 receptor signaling occurs in cells not normally expressing the IL-6 receptor. It has been suggested that IL-6 is intimately associated with two crucial aspects of depression, as well as central inflammation more broadly. First, the regulation of the local inflammatory response via its interactions with macrophage and glia melatonin production is coupled to local epigenetic modulation via methyl CpG-binding protein 2 (MeCP2). Second, the more systemic regulation of tryptophan availability occurs via the IL-6 induction of IDO. Coupled to its role in the regulation of autoimmune associated T-helper 17 cells and IL-17 production, IL-6 has wide and differential impacts on processes driving depression and a wider range of psychiatric and neurodegenerative conditions.
Language eng
DOI 10.1016/S1734-1140(13)71526-3
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
1115 Pharmacology And Pharmaceutical Sciences
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2013, Institute of Pharmacology Polish Academy of Sciences
Persistent URL http://hdl.handle.net/10536/DRO/DU:30071183

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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