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

Version 2 2024-06-03, 19:12
Version 1 2015-03-18, 09:30
journal contribution
posted on 2024-06-03, 19:12 authored by G Anderson, M Kubera, W Duda, W Lasoñz, Michael BerkMichael Berk, M Maes
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.

History

Journal

Pharmacological Reports

Volume

65

Pagination

1647-1654

Location

Switzerland

ISSN

2299-5684

eISSN

2299-5684

Language

English

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Copyright notice

2013, Institute of Pharmacology Polish Academy of Sciences

Issue

6

Publisher

POLISH ACAD SCIENCES INST PHARMACOLOGY