Cytokine production in bipolar affective disorder patients under lithium treatment

Background: Our knowledge concerning immune functioning in bipolar affective disorder (BAD) is limited, while lithiumʹs immunomodulatory effects seem multiple and conflicting. Our aim was to evaluate cytokine production and lithiumʹs effect on it in BAD patients, using ELISPOT technique as a sensitive tool. Methods: Cytokine (IL-2, IL-6, IL-10 and IFN-γ) production from isolated peripheral blood lymphocytes (PBLs) was evaluated (ELISPOT technique) in 40 euthymic BAD patients under chronic lithium treatment, in 20 healthy volunteers, and in 10 never medicated BAD patients before and after the introduction of lithium therapy. In all cases, cytokine plasma levels were also measured using ELISA. Results: BAD patients under chronic lithium treatment had significantly lower numbers of IL-2, IL-6, IL-10 and IFN-γ secreting cells compared to healthy volunteers. The number of cytokine secreting cells decreased in never medicated patients after 3 months of lithium treatment. In vitro stimulation of PBLs with lithium did not affect the number of cytokine secreting cells either in the patients or in the healthy volunteers. Conclusions: The significantly lower number of PBLs producing cytokines (IL-2, IL-6, IL-10 and IFN-γ) in euthymic BAD patients under chronic lithium treatment result from the long-term (over 3 months) lithium administration. In vitro stimulation of PBLs with lithium did not change the number of cytokine producing cells. Our findings may be useful in elucidating possible downregulatory effects of lithium in humans.