In vitro immunoregulatory effects of lithium in healthy volunteers

Rationale: There is now some evidence that major depression is associated w ith activation of the inflammatory response system (IRS). Lithium is effect ive in the treatment and prophylaxis of major depression and shows signific ant immunoregulatory functions. Objective: The aims of the present study we re to examine the in vitro effects of lithium on the unstimulated and lipol ysaccharide (LPS) + phytohemagglutinin (PHA)-induced production of proinfla mmatory cytokines, such as interleukin-6 (IL-6), IL-8, tumor necrosis facto r-alpha (TNF alpha) and interferon-gamma (IFN gamma), and negative immunore gulatory cytokines or proteins, such as IL-10 and the IL-1 receptor antagon ist (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 pr esence 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 r esults suggest that lithium has significant immunoregulatory effects by inc reasing the production of both proinflammatory cytokines (IFN gamma, TNF al pha and IL-8) and negative immunoregulatory cytokines or proteins (IL-10 an d the IL-1RA).