Objectives: To study the ex vivo interleukin (IL)-1 β 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 (24h) or not exposed to lipopolysaccharide (LPS) and/or graded concentrations of lithium chloride (LiCl). IL-1 β 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 β/IL-6 production ratio, i.e., low IL-1 β and high IL-6 production. Lithium treatment increased IL-1 β 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 β production and had minimal effects on IL-6 production. Conclusion: 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.

Bipolar disorder, IL-1β, IL-6, Lithium, Monocytes
dx.doi.org/10.1111/j.1399-5618.2007.00444.x, hdl.handle.net/1765/36757
Bipolar Disorders (English Edition, Print)
Erasmus MC: University Medical Center Rotterdam

Knijff, E.M, Nadine, B.M, Kupka, R.W, de Wit, H.J, Ruwhof, C, Akkerhuis, G.W, … Drexhage, H.A. (2007). An imbalance in the production of IL-1β and IL-6 by monocytes of bipolar patients: Restoration by lithium treatment. Bipolar Disorders (English Edition, Print), 9(7), 743–753. doi:10.1111/j.1399-5618.2007.00444.x