An imbalance in the production of IL-1β and IL-6 by monocytes of bipolar patients:: restoration by lithium treatment

Objectives: To study the ex vivo interleukin (IL)-1 beta and IL-6 production of monocytes in bipolar disorder (BD) patients in the absence/presence of lithium. Methods: Monocytes of outpatients with DSM-IV BD (n = 80, of whom 64 were lithium-treated) and of healthy control subjects (n = 59) were cultured in vitro and exposed (24 h) or not exposed to lipopolysaccharide (LPS) and/or graded concentrations of lithium chloride (LiCl). IL-1 beta and IL-6 production was assessed by enzyme-linked immunosorbent assay (ELISA) (supernatants). Results: Monocytes stimulated by LPS from non-lithium-treated bipolar patients were characterized by an abnormal IL-1 beta/IL-6 production ratio, i.e., low IL-1 beta and high IL-6 production. Lithium treatment increased IL-1 beta and decreased IL-6 production and thus restored the aberrant ratio. In vitro exposure of monocytes to LiCl did not have the same effects as lithium treatment: the procedure decreased IL-1 beta production and had minimal effects on IL-6 production. Conclusions: Blood monocytes have an altered proinflammatory status in BD. Lithium treatment restores this altered status. Short-term in vitro exposure of monocytes to lithium has other effects than lithium treatment.