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.

A relative resistance of T cells to dexamethasone in bipolar disorder.

OBJECTIVE: A relative resistance of immune cells to steroids has been established in patients with major depression (MD). In this study, we investigated the in vitro responsiveness of T cells to dexamethasone (DEX) of patients with bipolar disorder (BD). METHODS: T cells of outpatients with DSM-IV BD (n = 54) and of healthy control subjects (HC; n = 29) were isolated, cultured and stimulated with phytohemagglutinin (PHA) for 72 h. The suppressive effect of graded concentrations of DEX (5 x 10(-9)-10(-5) M) on PHA-induced CD25 (IL-2R) expression was measured by fluorescence-activated cell sorting (FACS) analysis. Data were correlated to the T-cell activation status in the peripheral blood of the same patients and to their diagnosis, current mood state, ultradian cycling pattern and current use of medication, including lithium. RESULTS: T cells of patients with BD were less sensitive to DEX-induced suppressive effects as compared with T cells of HC. These data were particularly evident at 10(-7) M DEX (mean % suppression +/- SEM BD: 18.9% +/- 3.5 versus HC: 35.8% +/- 4.7, p = 0.001). We found no correlations of this relative in vitro DEX resistance of T cells neither with the previously mentioned clinical characteristics nor with the actual activation status of the T cells in the BD patients. CONCLUSION: A relative T-cell resistance to steroids, as has been observed in MD previously, may be a trait phenomenon of BD, independent of mood state.

High numbers of circulating activated T cells and raised levels of serum IL-2 receptor in bipolar disorder.

BACKGROUND: Previously, we found an increased prevalence of thyroid autoantibodies in patients with bipolar disorder. In the present study, we investigated other signs of immune activation in bipolar patients, in particular an activation of the T cell system. METHODS: Fluorescence activated cell scanning (FACS) analysis was performed on lymphocytes of 64 outpatients with DSM-IV bipolar disorder using the T cell marker CD3 in combination with the activation markers MHC-class II, CD25, CD69 or CD71. In 34 patients, these assays were repeated after an interval of 2 years. In addition, T cell activation was determined by measuring serum soluble IL-2 receptor (sIL-2R) in 172 bipolar outpatients. Outcomes were compared with a healthy control group. RESULTS: Significantly higher numbers of circulating activated T cells and raised sIL-2R levels were found in euthymic, manic, and depressed bipolar patients when compared with healthy controls. In general, these abnormalities were stable over time. Manic patients showed significantly higher levels of sIL-2R in comparison with depressed patients. CONCLUSION: The T cell system was found to be activated in both symptomatic and euthymic patients with bipolar disorder. The pathophysiological significance of these findings remains to be explored.