Serum inflammatory cytokines in the progression of depression.
Qing Feng, Zhen Yuan, Qi An, Kang Wang, Xiaohui Liu
Frontiers in immunology January 1, 2026 Peer reviewed DOI: 10.3389/fimmu.2026.1808989 via PubMed
Summary
Depression is linked to immune dysregulation, with serum inflammatory cytokines like IL-1β and TNF-α playing significant roles in its development and treatment response. These cytokines affect brain function by activating immune pathways and disrupting neurotransmission. Clinical studies show correlations between inflammatory cytokine levels and depression severity, cognitive issues, and chronicity. Anti-inflammatory treatments and certain antidepressants may help by normalizing these cytokine pathways, suggesting their potential as targets for depression therapy.
Study at a glance
| Design | review |
|---|---|
| Key finding | Serum inflammatory cytokines are key links between peripheral inflammation and central nervous system dysfunction in depression. |
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.