Pro-Inflammatory Cytokines: Potential Links between the Endocannabinoid System and the Kynurenine Pathway in Depression

Author(s)

Zador, Ferenc ^{[1, 2]} ; Joca, Samia ^[3] ; Nagy-Grocz, Gabor ^{[4, 5]} ; Dvoracsko, Szabolcs ^{[1, 6]} ; Szucs, Edina ^{[1, 7]} ; Tomboly, Csaba ^[1] ; Benyhe, Sandor ^[1] ; Vecsei, Laszlo ^{[5, 8, 9]}

Affiliation

^[1] Biol Res Ctr, Inst Biochem, H-6726 Szeged - Hungary

^[2] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, Fac Med, H-1445 Budapest - Hungary

^[3] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C - Denmark

^[4] Univ Szeged, Fac Hlth Sci & Social Studies, H-6726 Szeged - Hungary

^[5] Univ Szeged, Dept Neurol, Albert Szent Gyorgyi Clin Ctr, Fac Med, H-6725 Szeged - Hungary

^[6] Univ Szeged, Dept Med Chem, H-6720 Szeged - Hungary

^[7] Univ Szeged, Doctoral Sch Theoret Med, Fac Med, H-6720 Szeged - Hungary

^[8] Univ Szeged, MTA SZTE Neurosci Res Grp, H-6725 Szeged - Hungary

^[9] Univ Szeged, Dept Neurol, Interdisciplinary Excellence Ctr, H-6725 Szeged - Hungary

• Document type: Review article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 11 JUN 2021.
• Web of Science Citations: 0

Abstract

Substance use/abuse is one of the main causes of depressive symptoms. Cannabis and synthetic cannabinoids in particular gained significant popularity in the past years. There is an increasing amount of clinical data associating such compounds with the inflammatory component of depression, indicated by the up-regulation of pro-inflammatory cytokines. Pro-inflammatory cytokines are also well-known to regulate the enzymes of the kynurenine pathway (KP), which is responsible for metabolizing tryptophan, a precursor in serotonin synthesis. Enhanced pro-inflammatory cytokine levels may over-activate the KP, leading to tryptophan depletion and reduced serotonin levels, which can subsequently precipitate depressive symptoms. Therefore, such mechanism might represent a possible link between the endocannabinoid system (ECS) and the KP in depression, via the inflammatory and dysregulated serotonergic component of the disorder. This review will summarize the data regarding those natural and synthetic cannabinoids that increase pro-inflammatory cytokines. Furthermore, the data on such cytokines associated with KP activation will be further reviewed accordingly. The interaction of the ECS and the KP has been postulated and demonstrated in some studies previously. This review will further contribute to this yet less explored connection and propose the KP to be the missing link between cannabinoid-induced inflammation and depressive symptoms. (AU)

• FAPESP's process: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants