In vitro immunoregulatory effects of lithium in healthy volunteers.
BACKGROUND
There is now some evidence that major depression is associated with activation of the inflammatory response system (IRS). Lithium is effective in the treatment and prophylaxis of major depression and shows significant immunoregulatory functions.


OBJECTIVE
The aims of the present study were to examine the in vitro effects of lithium on the unstimulated and lipolysaccharide (LPS) + phytohemagglutinin (PHA)-induced production of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma), and negative immunoregulatory cytokines or proteins, such as IL-10 and the IL-1 receptor antagonist (IL-1RA).


METHODS
The in vitro effects of lithium carbonate at low (10(-4) M and 10(-5) M) and therapeutic (10(-3) M) concentrations on the above cytokines and the IL-1RA were examined in nine healthy volunteers on whole blood supernatant cultured for 72 h.


RESULTS
Lithium (10(-3) M) in the presence of LPS+PHA significantly increased the stimulated production of IFNgamma, IL-8, TNFalpha, IL-1RA and IL-10. Lithium (10(-3) M) significantly increased the unstimulated production of IL-8 and IL-10.


CONCLUSIONS
The results suggest that lithium has significant immunoregulatory effects by increasing the production of both proinflammatory cytokines (IFNgamma, TNFalpha and IL-8) and negative immunoregulatory cytokines or proteins (IL-10 and the IL-1RA).
Maes
M
M
Clinical Research Center for Mental Health, University Department of Psychiatry, AZ Stuivenberg, Antwerp, Belgium. m.maes@unicall.be
Song
C
C
Lin
A H
AH
Pioli
R
R
Kenis
G
G
Kubera
M
M
Bosmans
E
E
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D016651:Lithium Carbonate / Q000494:pharmacology*; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D000276:Adjuvants, Immunologic; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016651:Lithium Carbonate; D007371:Interferon-gamma