The Effect of Ketamine on the Immune System in Patients with Treatment-Resistant Depression
Łukasz P. Szałach, Klaudia Ciesielska-Figlon, A. Daca, Wiesław Jerzy Cubała, K. Lisowska
International Journal of Molecular Sciences August 1, 2025 DOI: 10.3390/ijms26157500 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort with in vitro experiments Peer reviewed |
|---|---|
| Sample size | 18 |
| Population | Inpatients with treatment-resistant depression |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg iv |
| Duration | 24 hours |
| Topics | Depression Esketamine Ketamine |
| Citations | 7 |
| Key findings | Ketamine induces rapid, transient immune changes in treatment-resistant depression, including reduced T-cell activation and a sustained decrease in IL-8 levels. |
Abstract
Treatment-resistant depression (TRD) is associated with immune dysregulation. Ketamine, a rapid-acting antidepressant, may exert effects via immunomodulation. The aim was to examine ketamine’s impact on immune markers in TRD, including T-cell subsets, cytokines, and in vitro T-cell responses. Eighteen TRD inpatients received 0.5 mg/kg iv ketamine. Blood was sampled at baseline, 4 h, and 24 h to analyze T-cell phenotypes (CD28, CD69, CD25, CD95, HLA-DR) and serum cytokines (IL-6, IL-8, IL-10, TNF-α, IL-1β, IL-12p70). In vitro, PBMCs from TRD patients and controls were exposed to low (185 ng/mL) and high (300 ng/mL) ketamine doses. Ketamine induced a transient increase in total T cells and CD4+CD25+ and CD4+CD28+ subsets at 4 h, followed by a reduction in CD4+ and an increase in CD8+ T cells at 24 h, decreasing the CD4+/CD8+ ratio. Activation markers (CD4+CD69+, CD4+HLA-DR+, CD8+CD25+, CD8+HLA-DR+) declined at 24 h. Serum IL-10 increased, IL-6 decreased, and IL-8 levels—initially elevated—showed a sustained reduction. In vitro, high-dose ketamine enhanced the proliferation of TRD CD4+ T cells and dose-dependent IL-8 and IL-6 secretion from activated cells. Ketamine induces rapid, transient immune changes in TRD, including reduced T-cell activation and cytokine modulation. A sustained IL-8 decrease suggests anti-inflammatory effects and potential as a treatment-response biomarker.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 4
- Preliminary evidence that serum interleukin-6 is a candidate biomarker of response to esketamine in treatment-resistant depression. Journal of Psychopharmacology April 24, 2026
- Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders. CNS Spectrums September 28, 2026
- Appetite measures during ketamine administration in treatment-resistant mood disorders: a naturalistic study. Frontiers in Nutrition August 21, 2026
- Convergent neuroimmune signaling underlying rapid antidepressant response to ketamine and psychedelics. Molecular Psychiatry July 28, 2026
Cites 12
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Translational Psychiatry March 21, 2017
and 7 more in the library