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Published on: July 22, 2011
In vitro immunoregulatory effects of lithium in healthy volunteers
1Clinical Research Center for Mental Health, University Department of Psychiatry, AZ Stuivenberg, Antwerp, Belgium. m.maes@unicall.be
Insights
Lithium modulates the immune system by increasing the production of pro-inflammatory cytokines, such as interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha), and anti-inflammatory cytokines like interleukin-10 (IL-10). This highlights lithium's immunoregulatory potential in major depression.
Area of Science:
- Immunology
- Neuroscience
- Pharmacology
Background:
- Major depression is linked to inflammation.
- Lithium is a key treatment for depression with known immunoregulatory effects.
Purpose of the Study:
- To investigate lithium's in vitro impact on cytokine production.
- To assess effects on both unstimulated and stimulated immune responses.
Main Methods:
- Examined lithium carbonate's effect on whole blood supernatant from 9 healthy volunteers.
- Measured production of key cytokines (IL-6, IL-8, TNFalpha, IFNgamma) and IL-1RA.
Main Results:
- Therapeutic lithium (10(-3) M) significantly boosted stimulated IFNgamma, IL-8, TNFalpha, IL-1RA, and IL-10 production.
- Lithium also increased unstimulated IL-8 and IL-10 production.
Conclusions:
- Lithium demonstrates significant immunoregulatory functions.
- It enhances both pro-inflammatory and anti-inflammatory cytokine production, suggesting a complex immune modulation role.
Rationale:
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).
