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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)

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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.

Study Year Design Participants
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress 2017 Preclinical animal study
Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression Susceptible mice in the social defeat stress model 2016 Animal experimental study
Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression Wistar-Kyoto (WKY) rats and Wistar control rats 2020 Preclinical study
Effect of Ketamine on LTP and NMDAR EPSC in Hippocampus of the Chronic Social Defeat Stress Mice Model of Depression Male C57BL/6J mice 2018 Controlled laboratory experiment

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