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.