Circulating T helper 17 and IFN-γ positive Th17 cells in Major Depressive Disorder

Abstract Background Evidence indicates that pro-inflammatory Th17 and Th1 cells are involved in major depressive disorder (MDD) pathogenesis. Development of Th17 and Th1 are regulated by IL-6 and IFN-γ, respectively. In this study, the levels of IL-6 and IFN-γ, and mRNA expression of related signaling components and, Th17/Th1 transcription factors were investigated in MDD patients with/without selective serotonin reuptake inhibitor (SSRI) medication. Materials and methods Forty-six patients and 38 healthy controls (HCs) were recruited. Twenty patients were received the SSRI (sertraline 50–200 mg/day) for at least 1 year, and 26 patients were not received medication. Expression of IL-6R, IFN-γR, JAK1, JAK2, TYK2, STAT1, STAT3, T-bet and RORγt were assessed with Real-Time-PCR. Serum and supernatant levels of IL-6 and IFN-γ were determined using ELISA. Results and discussion The serum and supernatant levels of IL-6 were increased in patients without (SSRI−) compared with HCs, while its levels was reduced in SSRI+. Elevated expressions of IL-6R, STAT3 and RORγt were observed in SSRI− compared with HCs. Expressions of IL-6R, STAT3, RORγt and IFN-γR, were decreased in SSRI+ compared to SSRI− patients. Conclusion Increased IL-6 involved in MDD, and SSRI regulates IL-6 pathway and IL-6 production. MDD patients may benefit from IL-6/IL-6R targeted therapeutic intervention.

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Serum Interleukin Levels and Insulin Resistance in Major Depressive Disorder

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527317666180720155300 ◽

2018 ◽

Vol 17 (8) ◽

pp. 618-625 ◽

Cited By ~ 7

Author(s):

Hussein Kadhem Al-Hakeim ◽

Sadiq Neama Al-Kufi ◽

Arafat Hussein Al-Dujaili ◽

Michael Maes

Keyword(s):

Insulin Resistance ◽

Major Depressive Disorder ◽

Immune System ◽

Depressive Disorder ◽

Serum Levels ◽

Major Depressive ◽

Glucose Ratio ◽

Cytokine Levels ◽

Ifn Γ ◽

Tgf Β1

Background & Objective: Major depressive disorder (MDD) has been associated with inflammatory processes, including increased cytokine levels, even in individuals who are otherwise physically healthy, while some MDD patients may show insulin resistance (IR). Method: However, correlations between cytokines and IR parameters have not been studied extensively in MDD. In the present study, we measured IL-1β, IL-4, IFN-γ, TGF-β1, insulin and glucose in 63 MDD patients and 27 healthy controls. The associations between cytokine levels and IR were examined. Results: The results revealed a significant increase (p<0.05) in serum levels of IL-1β, IL-4, IFN-γ, TGF-β1, insulin, insulin/glucose ratio, and insulin resistance (HOMA2IR) in MDD patients as compared with controls. There was a significant correlation between HOMA2IR with both IFN-γ (ρ=0.289, p<0.05) and TGF-β1 (ρ=0.364, p<0.05). Conclusion: The present study further confirms that MDD is accompanied by activation of the immune system with significant elevations in the levels of four cytokines. These results indicate stimulation of the immune system and increased IR and modulation of IR by increased cytokine levels in MDD. These findings show that immune activation and associated IR are a new drug target in depression.

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The circulating levels of CD4+ t helper cells are higher in bipolar disorder as compared to major depressive disorder

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2018.03.004 ◽

2018 ◽

Vol 319 ◽

pp. 28-36 ◽

Cited By ~ 14

Author(s):

Karlijn Becking ◽

Bartholomeus C.M. Haarman ◽

Laura Grosse ◽

Willem A. Nolen ◽

Stephan Claes ◽

...

Keyword(s):

Bipolar Disorder ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

T Helper Cells ◽

T Helper ◽

Major Depressive ◽

Helper Cells ◽

Circulating Levels

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Serum interferon-gamma level is associated with drug-naïve major depressive disorder

SAGE Open Medicine ◽

10.1177/2050312120974169 ◽

2020 ◽

Vol 8 ◽

pp. 205031212097416

Author(s):

Sohel Daria ◽

Maliha Afrin Proma ◽

Mohammad Shahriar ◽

Sardar Mohammad Ashraful Islam ◽

Mohiuddin Ahmed Bhuiyan ◽

...

Keyword(s):

Risk Assessment ◽

Major Depressive Disorder ◽

Major Depression ◽

Depressive Disorder ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Major Depressive ◽

Early Risk ◽

Ifn Γ

Objectives: Major depressive disorder is a leading heterogeneous psychiatric illness manifested by persistent low mood, a feeling of sadness, and diminished interest in daily activities. Many biological, genetic, and social factors are thought to be linked with depression. But any suitable early risk assessment markers are absent for this illness. Therefore, we aimed to investigate the serum levels of IFN-γ in major depressive disorder patients to further investigate the association between serum levels of this cytokine and major depression. Methods: This prospective case-control study enrolled 120 major depressive disorder patients and 100 healthy controls matched by age, sex, and body mass index. A qualified psychiatrist diagnosed the major depressive disorder patients and evaluated healthy controls according to the Diagnostic and Statistical Manual of Mental Health Disorders (5th ed.; DSM-5). The Hamilton depression rating scale was applied for all the study participants to measure the severity of depression. Serum IFN-γ levels were measured by a commercially available enzyme-linked immunosorbent assay kit (Boster Biological Technology, Pleasanton, CA, USA). Results: This study observed that serum IFN-γ levels were significantly decreased in major depressive disorder patients compared to healthy controls. A significant negative correlation ( r = −0.375; p < 0.001) was obtained between serum IFN-γ levels and Hamilton depression scores. Receiver operating characteristic analysis showed good diagnostic performance of lowered serum IFN-γ levels in depression with an area under the curve at 0.790. Conclusion: We suggest the altered serum IFN-γ levels are associated with the pathophysiology of depression. The reduced levels of serum IFN-γ might be used as an early risk assessment tool for major depression.

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The effects of phenanthrene exposure on Treg and Th17 cells related cytokines in female rats

Toxicology Research ◽

10.1093/toxres/tfaa030 ◽

2020 ◽

Vol 9 (3) ◽

pp. 283-289

Author(s):

Haitao Ma ◽

Huizhen Guo ◽

Wenwen Zhang ◽

Fengjing Hu ◽

Yushan Huang ◽

...

Keyword(s):

Th17 Cells ◽

Corn Oil ◽

Treg Cells ◽

Interferon Γ ◽

Female Rats ◽

Female Rat ◽

T Helper ◽

T Helper 17 ◽

Immune Impairment ◽

Ifn Γ

Abstract Phenanthrene (Phe) female rat model was established to explore the mechanism of Phe on immune impairment. The rats were randomly divided into three groups, including control (C), low (L), and high (H) groups. Phe was supplied to L and H groups at the dose of 180 and 900 mg/kg orally at first day and with the dose of 90 and 450 mg/kg by intraperitoneal injection at the last 2 days. The C group was enriched with the same volume of corn oil. The liver tissue was collected. Then, the protein and mRNA expressions of interleukin (IL)-35 and the concentration IL-17 were detected to evaluate the function of regulatory T cells (Treg cells) and T helper 17 cells (Th17 cells). In addition, IL-1β and interferon-γ (IFN-γ) were analyzed to evaluate the immune impairment. The results showed that the protein and mRNA expressions of IL-35 decreased significantly in H groups (P < 0.05). Meanwhile, there were significant increases in IL-17, IFN-γ and IL-1β in the liver of H group (P < 0.05). This study demonstrated that Phe exposure might be associated with the immune impairment via changing inflammatory mediators including IL-35 and IL-17 in female rats.

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Cytokines that Modulate the Differentiation of Th17 Cells in Autoimmune Uveitis

Journal of Immunology Research ◽

10.1155/2021/6693542 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Kailei Guo ◽

Xiaomin Zhang

Keyword(s):

Th17 Cells ◽

Transforming Growth Factor ◽

Therapeutic Targets ◽

Transforming Growth Factor Β1 ◽

T Helper ◽

Immune Disease ◽

T Helper 17 ◽

Autoimmune Uveitis ◽

Ifn Γ ◽

Tgf Β1

Increasing evidence has suggested that T helper 17 (Th17) cells play a central role in the pathogenesis of ocular immune disease. The association between pathogenic Th17 cells and the development of uveitis has been confirmed in experimental and clinical studies. Several cytokines affect the initiation and stabilization of the differentiation of Th17 cells. Therefore, understanding the mechanism of related cytokines in the differentiation of Th17 cells is important for exploring the pathogenesis and the potential therapeutic targets of uveitis. This article briefly describes the structures, mechanisms, and targeted drugs of cytokines—including interleukin (IL)-6, transforming growth factor-β1 (TGF-β1), IL-1β, IL-23, IL-27, IL-35, IL-2, IL-4, IL-21, and interferon (IFN)-γ—which have an important influence on the differentiation of Th17 cells and discusses their potential as therapeutic targets for treating autoimmune uveitis.

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Th17 Cells in Depression: Are They Crucial for the Antidepressant Effect of Ketamine?

Frontiers in Pharmacology ◽

10.3389/fphar.2021.649144 ◽

2021 ◽

Vol 12 ◽

Author(s):

Meiying Cui ◽

Wanlin Dai ◽

Jing Kong ◽

Hongzhi Chen

Keyword(s):

Major Depressive Disorder ◽

Depressive Symptoms ◽

Depressive Disorder ◽

Th17 Cells ◽

Cell Function ◽

Immune Cell ◽

Cell Subset ◽

Antidepressant Medication ◽

Antidepressant Effect ◽

Major Depressive

Background: Major depressive disorder is associated with inflammation and immune processes. Depressive symptoms correlate with inflammatory markers and alterations in the immune system including cytokine levels and immune cell function. Th17 cells are a T cell subset which exerts proinflammatory effects. Th17 cell accumulation and Th17/Treg imbalances have been reported to be critical in the pathophysiology of major depressive disorder and depressive-like behaviors in animal models. Th17 cells are thought to interfere with glutamate signaling, dopamine production, and other immune processes. Ketamine is a newly characterized antidepressant medication which has proved to be effective in rapidly reducing depressive symptoms. However, the mechanisms behind these antidepressant effects have not been fully elucidated.Method: Literature about Th17 cells and their role in depression and the antidepressant effect of ketamine are reviewed, with the possible interaction networks discussed.Result: The immune-modulating role of Th17 cells may participate in the antidepressant effect of ketamine.Conclusion: As Th17 cells play multiple roles in depression, it is important to explore the mechanisms of action of ketamine on Th17 cells and Th17/Treg cell balance. This provides new perspectives for strengthening the antidepressant effect of ketamine while reducing its side effects and adverse reactions.

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