The effects of lithium on ex vivo cytokine production

• Published in: Biological psychiatry (1969) Vol. 50; no. 3; pp. 217 - 224
• Main Authors: Rapaport, Mark Hyman, Manji, Husseini K
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2001; Elsevier Science
• Subjects: Adult; Aged; Antipsychotic Agents - pharmacology; Biological and medical sciences; Bipolar Disorder - drug therapy; Bipolar Disorder - immunology; Bipolar Disorder - metabolism; Cells, Cultured; cyclic AMP; Cyclic AMP - metabolism; Cytokines; Cytokines - immunology; Cytokines - metabolism; Female; Humans; IL-2; immunology; lithium; Lithium - pharmacology; Male; Medical sciences; Middle Aged; myo-inositol; Neuropharmacology; Pharmacology. Drug treatments; Phosphoric Monoester Hydrolases - metabolism; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; lithium; cyclic AMP; IL-2; Cytokines; immunology; myo-inositol; Human; Cell culture; Immunomodulation; Secretion; Cytokine; Cyclic AMP; Lithium; In vitro; Biological activity; Interleukin 4; Ex vivo; Interleukin 2; Mood stabilizer; Interleukin 10; Production
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(01)01144-1

Background: Studies suggest that lithium may have profound immunomodulatory effects in animal models as well as in humans. Methods: In this study, whole blood cultures from normal control subjects were established for 5 days and the effects of lithium on cytokine production were investigated. Because many of lithium’s actions have been postulated to be modulated through phosphoinositide (PI), protein kinase C (PKC) and cyclic adenosine monophosphate (c-AMP) signaling pathways, the effects of myo-inositol and prostaglandin E 2, alone or in combination with lithium, were also investigated. Results: We found that lithium caused an increase in interleukin-4 and interleukin-10 levels, traditionally classified as T-helper lymphocyte type-2 cytokines, and a decrease in interleukin-2 and interferon-γ levels, traditionally classified as T-helper lymphocyte type-1 (TH-1) cytokines. This shift cannot be fully explained by lithium’s actions on the PI, PKC, or c-AMP messenger systems. Conclusions: Monocytes exposed to lithium in the presence of a mitogen for 5 days produced a shift toward the production of TH-2 cytokines and away from the production of TH-1 cytokines. The study suggests that lithium may have complex time-dependent effects on immune function.