Differential effect of interferon-alpha treatment on AEA and 2-AG levels.
2-Aracgidonoylglycerol (2-AG)
Anandamide (AEA)
Cytokines
Depression
Endocannabinoid system
Hepatitis C
IFN-α-induced depression
Immune system
Inflammation
Interferon-α (IFN-α)
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
03
03
2020
revised:
14
07
2020
accepted:
23
08
2020
pubmed:
30
8
2020
medline:
28
4
2021
entrez:
30
8
2020
Statut:
ppublish
Résumé
The endocannabinoid (eCB) system is one of the key players in immunoregulation, and reduced activity of the eCB system has been linked with depressive-like behaviours in animal studies and depression in clinical samples. There is a well-established link between immune activation and depression, such as following the administration of the pro-inflammatory cytokine, interferon-α (IFN-α), used to treat hepatitis C viral (HCV) infection. However, the role of peripheral endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), following immunotherapy with IFN-α and in IFN-α -induced depression, have not been examined yet. In this study, we investigated whether circulating AEA and 2-AG were modified by treatment with IFN-α and whether they were involved in the development of IFN-α-induced depression. We also explored whether circulating eCBs were associated with peripheral cytokines during and after IFN-α treatment. We measured serum concentrations of AEA and 2-AG using High Performance Liquid Chromatography with Tandem Mass Spectrometry, and serum concentrations of cytokines using Meso Scale Discovery electrochemiluminescence V-PLEX assay, in 70 patients with HCV infection and 41 healthy subjects. We assessed HCV patients at baseline, IFN-α-treatment weeks (TW) 4 and 24, end of treatment (END) and at six months follow-up (FU). We assessed depression using M.I.N.I. International Neuropsychiatric Interview. We found a different pattern of change in peripheral AEA and 2-AG during and after IFN-α treatment. Whilst 2-AG increased earlier in immunotherapy (TW4), remained elevated throughout treatment, and reduced at six months follow-up (FU), AEA increased later in treatment (TW24) and remained elevated six months post-treatment. We also found that baseline levels of AEA were lower in HCV patients compared with healthy controls, whereas there were no differences in 2-AG levels. Interestingly, AEA, but not 2-AG, was significantly, negatively correlated with interleukin (IL)-2 and IL-17a at six months follow-up. We did not find any difference in both eCBs between patients with and without IFN-α-induced depression, at any time point. Our findings suggest that AEA and 2-AG are involved in different stages of immunoregulation following IFN-α treatment, where AEA might be involved in chronic inflammation. Lack of association between peripheral eCBs and IFN-α-induced depression suggests that different biological mechanisms may underpin inflammation-induced depression compared with classic "psychiatric" depression, or that any changes in the eCB system in depression may not be captured by peripheral AEA and 2-AG.
Identifiants
pubmed: 32860939
pii: S0889-1591(20)30255-5
doi: 10.1016/j.bbi.2020.08.024
pmc: PMC7575143
pii:
doi:
Substances chimiques
Cytokines
0
Endocannabinoids
0
Interferon-alpha
0
Silver
3M4G523W1G
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
248-258Subventions
Organisme : Medical Research Council
ID : G108/603
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N029488/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J002739/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Dr Forton has received speaker consultancy fees from companies that market drugs to treat hepatitis C, including AbbVie, Gilead, BMS and Janssen. He has received funding for trials from Merck. Dr Kosh Agarwal has received fees from companies that market drugs to treat Hepatitis C, including AbbVie, Gilead, Astellas, Intercept, Janssen, Merck and Achillon, and has received grants from AbbVie, Gileas, BMS and Roche. Prof. Pariante. Dr Mondelli and Dr. Zunszain have received research funding from Johnson & Johnson as part of a program of research on depression and inflammation, and research funding from the Medical Research Council (UK) and the Wellcome Trust for research on depression and inflammation as part of two large consortia that also include Johnson & & Johnson, GSK and Lundbeck. Dr Mondelli is also funded by MQ: Transforming Mental Health (Grant: MQBF1). The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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