In vitro immunoregulatory effects of lithium in healthy volunteers

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 (TNF alpha) and interferon-gamma (IFN gamma), 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 IFN gamma, IL-8, TNF alpha, 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 (IFN gamma, TNF alpha and IL-8) and negative immunoregulatory cytokines or proteins (IL-10 and the IL-1RA).