Monocyte-derived dendritic cells in bipolar disorder.

BACKGROUND: Dendritic cells (DC) are key regulators of the immune system, which is compromised in patients with bipolar disorder. We sought to study monocyte-derived DC in bipolar disorder. METHODS: Monocytes purified from blood collected from DSM-IV bipolar disorder outpatients (n = 53, 12 without lithium treatment) and healthy individuals (n = 34) were differentiated into DC via standard granulocyte-macrophpage colony-stimulating factor/interleukin-4 culture (with/without 1, 5, and 10 mmol/L lithium chloride). The DC were analyzed for DC-specific and functional markers and for T-cell stimulatory potency. RESULTS: Monocytes of bipolar patients showed a mild hampering in their differentiation into fully active DC, showing a weak residual expression of the monocyte marker CD14 and a relatively low potency to stimulate autologous T cells. Lithium treatment abolished this mild defect, and monocyte-derived DC of treated bipolar patients showed signs of activation (i.e., an up-regulated potency to stimulate autologous T cells and a higher expression of the DC-specific marker CD1a). This activated phenotype contrasted with the suppressed phenotype of monocyte-derived DC exposed to lithium in vitro (10 mmol/L) during culture. CONCLUSIONS: Dendritic cells show mild aberrancies in bipolar disorder that are fully restored to even activation after in vivo lithium treatment.

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

OBJECTIVES: To study the ex vivo interleukin (IL)-1beta 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-1beta 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-1beta/IL-6 production ratio, i.e., low IL-1beta and high IL-6 production. Lithium treatment increased IL-1beta 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-1beta 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.