Serum inflammatory cytokines in the progression of depression.
Qing Feng, Zhen Yuan, Qi An, Kang Wang, Xiaohui Liu
Frontiers in Immunology 2026 DOI: 10.3389/fimmu.2026.1808989 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression |
| Keywords | Il-1β Tnf-α Inflammatory cytokines Neuroimmune interaction Neuroinflammation |
| Citations | 1 |
| Key findings | Serum inflammatory cytokines are key mediators linking peripheral inflammation to depression-related neuropathophysiology and may serve as therapeutic targets. |
Abstract
Depression is increasingly recognized as a multifactorial disorder in which immune dysregulation contributes substantially to disease initiation, progression, and treatment response. Among the immune mediators implicated, serum inflammatory cytokines-including IL-1β, IL-6, TNF-α, IFN-γ, and C-reactive protein-have emerged as key links between peripheral inflammation and central nervous system dysfunction. These cytokines influence depression-related pathophysiology by activating innate immune signaling pathways, including TLR4, NF-κB, MAPK, and the NLRP3 inflammasome, while also reshaping tryptophan-kynurenine metabolism through IDO1 and TDO2. The resulting alterations impair monoaminergic neurotransmission, enhance glutamatergic excitotoxicity, suppress BDNF-dependent neuroplasticity, and promote microglia-mediated neuroinflammation. Clinical studies further associate inflammatory cytokine profiles with symptom severity, cognitive dysfunction, suicidality, and illness chronicity, supporting their potential value as biologically informative markers in depression. Emerging therapeutic evidence indicates that anti-inflammatory bioactive compounds, conventional antidepressants with immunomodulatory properties, and rapid-acting agents such as ketamine may partially exert their effects by normalizing cytokine-associated pathways. This review summarizes current mechanistic and clinical evidence linking serum inflammatory cytokines to depression and highlights their potential as therapeutic targets in precision psychiatry.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cites 3
- Sustained antidepressant effect of ketamine through NMDAR trapping in the LHb Nature October 18, 2023
- Effect of ketamine combined with DHA on lipopolysaccharide-induced depression-like behavior in rats. International Immunopharmacology August 1, 2019
- Decoding Depression: Insights from Glial and Ketamine Regulation of Neuronal Burst Firing in Lateral Habenula. Cold Spring Harbor Symposia on Quantitative Biology 2018