The effects of lithium on ex vivo cytokine production

Background: Studies suggest that lithium may have profound immunomodulatory effects in animal models as well as in humans. Methods: lit this study, whole blood cultures from normal control subjects were established for 5 days and the effects of lithium on cytokine producti on were investigated. Because many of lithium's actions have been postulate d 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, w ere also investigated. Results: We found that lithium caused an increase in interleukin-4 and inte rleukin-10 levels, traditionally classified as T-helper lymphocyte type-2 c ytokines, and a decrease in interleukin-2 and interferon-gamma levels, trad itionally classified as T-helper lymphocyte type-1 (TH-1) cytokines. This s hift cannot be fully explained by lithium's actions on the PI, PKC, or c-AM P 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 fr om the production of TH-1 cytokines. The study suggests that lithium may ha ve complex time-dependent effects on immune function. (C) 2001 Society of B iological Psychiatry.