Altered serum levels of TNF-α, IL-6 and IL-18 in manic, depressive, mixed state of bipolar disorder patients

• Elevated serum TNF-α and IL-6 levels in manic, depressive, mixed state BD patients.
• Elevated serum IL-18 levels in depressive state BD patients.
• A positive correlation between IL-6 levels and YMRS scores in manic state patients.
• A positive correlation between IL-6 levels and YMRS scores in mixed state patients.

Bipolar disorder (BD) is associated with alterations of cytokines in the immune system. The aim of this study was to assess the serum levels of TNF-α, IL-6 and IL-18 in manic, depressive, mixed state patients of BD. The correlations between the serum cytokines levels with the demographic characteristics and the psychiatric symptoms were also assessed. We measured serum TNF-α, IL-6 and IL-18 levels using an enzyme-linked immunosorbent assay (ELISA) from 59 BD patients (37 in manic state, 12 in depressive state, 10 in mixed state) and 80 healthy control subjects. The psychotic symptoms of BD were assessed using the Hamilton Depression Scale (HAMD) and the Young Mania Rating Scale (YMRS). The results showed that serum TNF-α and IL-6 levels in manic, depressive and mixed state BD patients were significantly higher than that in controls, while serum IL-18 level was only significantly higher in depressive patients. Serum IL-6 level was significantly positively correlated with YMRS scores in manic episode as well as in mixed episode. When gender and age were added as potentially confounding covariate terms, the differences between controls and each mood state patients were still significant. Our findings provided additional evidence that elevated TNF-α, IL-6 and IL-18 pathway activities may be involved in the psychopathology of BD. Due to the lack of controlling important confounding factors, such as BMI, smoking status and alcohol use, further studies are required to confirm the roles of TNF-α, IL-6 and IL-18.