{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:07:47Z","timestamp":1792519667973,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T00:00:00Z","timestamp":1754179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010609","name":"statutory funds of the Medical University of Gda\u0144sk","doi-asserted-by":"publisher","award":["ST-02-0039\/07\/221"],"award-info":[{"award-number":["ST-02-0039\/07\/221"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010609","name":"statutory funds of the Medical University of Gda\u0144sk","doi-asserted-by":"publisher","award":["01-423\/08\/262"],"award-info":[{"award-number":["01-423\/08\/262"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010609","name":"Young Researchers","doi-asserted-by":"publisher","award":["ST-02-0039\/07\/221"],"award-info":[{"award-number":["ST-02-0039\/07\/221"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010609","name":"Young Researchers","doi-asserted-by":"publisher","award":["01-423\/08\/262"],"award-info":[{"award-number":["01-423\/08\/262"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s 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-\u03b1, IL-1\u03b2, 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\u2014initially elevated\u2014showed 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.<\/jats:p>","DOI":"10.3390\/ijms26157500","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"7500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Effect of Ketamine on the Immune System in Patients with Treatment-Resistant Depression"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5774-3927","authenticated-orcid":false,"given":"\u0141ukasz P.","family":"Sza\u0142ach","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"},{"name":"Department of Psychiatry, Faculty of Medicine, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Ciesielska-Figlon","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1485-3090","authenticated-orcid":false,"given":"Agnieszka","family":"Daca","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-8454","authenticated-orcid":false,"given":"Wies\u0142aw J.","family":"Cuba\u0142a","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6086-0024","authenticated-orcid":false,"given":"Katarzyna A.","family":"Lisowska","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1124\/pr.117.014977","article-title":"International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets","volume":"70","author":"Caraci","year":"2018","journal-title":"Pharmacol. 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