Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder

Background: The role of cytokines in bipolar disorder is still controversial. Although a few studies have found alterations of cytokines in bipolar disorder, their findings were inconsistent. The aim of this study was to determine whether the cytokines are involved in the pathophysiology of bipolar disorder. Methods: A total of 37 manic patients with bipolar disorder and 74 control subjects were recruited. The mitogen-induced production of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6), IL-4, interferon (IFN)-gamma, and IL-2 was measured using quantitative sandwich ELISA at the time of admission and 6 weeks after mood stabilizer treatment. Results: IL-6 and TNF-alpha production of bipolar manic patients was significantly higher than those of normal controls, while IL-4 values of the patients were significantly lower than normal controls. IL-6/IL-4, TNF-alpha/IL-4, IL-2/IL-4, and IFN-gamma/IL-4 ratios were significantly higher in bipolar manic patients than in normal controls. After 6 weeks of treatment, the levels of IL-6 significantly decreased compared with baseline. Limitations: The effect of various types of mood stabilizers on cytokine production should be considered. Conclusions: These findings suggest that the increased activity of pro-inflammatory cytokines and an imbalance between pro-inflammatory and anti-inflammatory cytokines may play a role in the pathophysiology of bipolar disorder.