{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:28:41Z","timestamp":1790742521820,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Institute for Psychobiology in Israel"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This narrative review examines lithium\u2019s effects on immune function, inflammation and cell survival, particularly in bipolar disorder (BD) in in vitro studies, animal models and clinical studies. In vitro studies show that high lithium concentrations (5 mM, beyond the therapeutic window) reduce interleukin (IL)-1\u03b2 production in monocytes and enhance T-lymphocyte resistance, suggesting a protective role against cell death. Lithium modulates oxidative stress in lipopolysaccharide (LPS)-activated macrophages by inhibiting nuclear factor (NF)-\u0199B activity and reducing nitric oxide production. At therapeutically relevant levels, lithium increased both pro-inflammatory [interferon (INF)-\u03b3, IL-8 and tumor necrosis factor (TNF)-\u03b1)] and anti-inflammatory (IL-10) cytokines on whole blood supernatant culture in healthy volunteers, influencing the balance of pro- and anti-inflammatory responses. Animal models reveal lithium\u2019s potential to alleviate inflammatory diseases by reducing pro-inflammatory cytokines and enhancing anti-inflammatory responses. It also induces selective macrophage death in atherosclerotic plaques without harming other cells. In primary rat cerebellum cultures (ex vivo), lithium prevents neuronal loss and inhibits astroglial growth, impacting astrocytes and microglia. Clinical studies show that lithium alters cytokine profiles and reduces neuroinflammatory markers in BD patients. Chronic treatment decreases IL-2, IL-6, IL-10 and IFN-\u03b3 secretion from peripheral blood leukocytes. Lithium response correlates with TNF-\u03b1 levels, with poor responders showing higher TNF-\u03b1. Overall, these findings elucidate lithium\u2019s diverse mechanisms in modulating immune responses, reducing inflammation and promoting cell survival, with significant implications for managing BD and other inflammation-related conditions. Yet, to better understand the drug\u2019s impact in BD and other inflammatory\/neuroinflammatory conditions, further research is warranted to appreciate lithium\u2019s therapeutic potential and its role in immune regulation.<\/jats:p>","DOI":"10.3390\/ijms252413277","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T03:14:58Z","timestamp":1733886898000},"page":"13277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Lithium, Inflammation and Neuroinflammation with Emphasis on Bipolar Disorder\u2014A Narrative Review"],"prefix":"10.3390","volume":"25","author":[{"given":"Odeya","family":"Damri","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Zlotowski Center for Neuroscience and Zelman Center\u2014The School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galila","family":"Agam","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Zlotowski Center for Neuroscience and Zelman Center\u2014The School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"ref_1","first-page":"518","article-title":"Lithium salts in the treatment of psychotic excitement. 1949","volume":"78","author":"Cade","year":"2000","journal-title":"Bull World Health Organ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/sj.tpj.6500245","article-title":"Pharmacogenetics and bipolar disorder","volume":"4","author":"Mamdani","year":"2004","journal-title":"Pharmacogenomics J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1001\/archpsyc.57.2.187","article-title":"Does lithium treatment still work? 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