期刊
PHARMACOLOGICAL REPORTS
卷 65, 期 6, 页码 1647-1654出版社
POLISH ACAD SCIENCES INST PHARMACOLOGY
DOI: 10.1016/S1734-1140(13)71526-3
关键词
depression; interleukin-6; indoleamine 2,3-dioxygenase; cytokines; melatonin; inflammation; oxidative stress; neuroprogression
资金
- Founds for Statutory Activity of the Institute of Pharmacology, Polish Academy of Sciences
- Jagielonian University, Krakow, Poland
- [POIG. 01.01.02-12-004/09]
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 v i a methyl CpG-binding protein 2 (MeCP2). Second, the more systemic regulation of tryptophan availability occurs v i a 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.
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