ArticleEuropean cytokine network
TNFα mediates stress-induced depression by upregulating indoleamine 2,3-dioxygenase in a mouse model of unpredictable chronic mild stress.
Article in European cytokine network. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 121 citations in OpenAlex.
- TNF-α levels in first-episode, drug-naïve patients with major depressive disorder: a case-control study and meta-analysis.BMC psychiatry · 2026Pooled it
- Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review.International journal of molecular sciences · 2016Pooled it
- Relationship of immune-inflammatory pathway and stress-induced depression with neural regeneration.Neural regeneration research · 2026Article
- Continuous OFT-Based Behavioral Phenotyping Reveals Neural Stem Cell-Associated Shifts in Depression-like Mice.Brain sciences · 2026Article
- Inflammatory models of depression in rodents and humans.Frontiers in psychiatry · 2026Review
- Lactobacillus fermentum ATCC 9338 ameliorates immune dysregulation via indoleamine 2, 3-dioxygenase through modulating gut microbial diversity of chronic unpredictable mild stressed mouse.Metabolic brain disease · 2025Article
- Oxiracetam ameliorates neurological function after traumatic brain injury through competing endogenous RNA regulatory network.Psychopharmacology · 2025Article
- Role of Probiotics in Depression: Connecting Dots of Gut-Brain-Axis Through Hypothalamic-Pituitary Adrenal Axis and Tryptophan/Kynurenic Pathway involving Indoleamine-2,3-dioxygenase.Molecular neurobiology · 2025Review
- Relationship Between Obesity and Depression Considering the Inflammatory Theory.International journal of molecular sciences · 2025Review
- Can infliximab serve as a new therapy for neuropsychiatric symptoms?Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controls.Scientific reports · 2025Article
- Article
- Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.Pharmacological reviews · 2024Review
- Dual Approach to Depression: The Combined Efficacy of Intermittent Hypoxia and Fluoxetine in Modulating Behavioral and Inflammatory Responses.Biomedicines · 2024Article
- Synergistic Effect of Coenzyme Q10 and L-Carnitine on Gliosis and Anhedonia, in a Rat Model of Multiple Sclerosis: An Immunohistochemical Study.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2024Article
- Biomarkers Associated with Depression Improvement in Veterans with Gulf War Illness Using the Low-Glutamate Diet.Nutrients · 2024Article
- Inhibition of Indoleamine 2,3-Dioxygenase Exerts Antidepressant-like Effects through Distinct Pathways in Prelimbic and Infralimbic Cortices in Rats under Intracerebroventricular Injection with Streptozotocin.International journal of molecular sciences · 2024Article
- Immune-Targeted Therapies for Depression: Current Evidence for Antidepressant Effects of Monoclonal Antibodies.The Journal of clinical psychiatry · 2024Review
- Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease.International journal of molecular sciences · 2024Review
- Advancing preclinical chronic stress models to promote therapeutic discovery for human stress disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Depression is often preceded by exposure to stressful life events. Chronic stress causes perturbations in the immune system, and up-regulates production of proinflammatory cytokines, which has been proposed to be associated with the pathogenesis of clinical depression. However, the potential mechanisms by which stress-induced proinflammatory cytokines lead to the development of depression are not well understood. Here, we sought to screen the main proinflammatory cytokines and the potential mechanisms linking inflammation to depression-like behavior during unpredictable, chronic, mild stress (UCMS), in vivo. Mice were allocated into four groups in each separate experiment: saline-control, saline-UCMS, drug-control and drug-UCMS. Development of depression-like behavior was reflected as a reduction in sucrose preference, and increased immobility in both the forced swim and tail suspension tests. The following drugs were administered intraperitoneally: the pan-anti-inflammatory tetracycline derivative, minocycline (30 mg/kg, daily), the tumor necrosis factor (TNF)α monoclonal antibody, infliximab (10 mg/kg, twice weekly), and the indoleamine 2, 3-dioxygenase (IDO) inhibitor, 1-methyltryptophan (1-MT, 10 mg/mouse, daily). Plasma TNFα, IL-1β and IL-18 increased significantly after the four-week UCMS exposure. Pretreatment of mice with minocycline completely blocked any upregulation. Concurrent with development of depression-like behaviors, the concentration of TNFα in plasma and the cerebral cortex increased remarkably. The tryptophan-degrading enzyme IDO was up-regulated in the cortex following UCMS exposure. Treatment of mice with minocycline, infliximab or 1-MT prevented the development of depression-like behaviors. Furthermore, blockade of TNFα inhibited expression of IDO and protected cortical neurons from UCMS-induced damage. These results suggest that TNFα plays a critical role in mediating UCMS-induced depression through up-regulation of IDO and subsequent damage of cortical neurons.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.