Different levels of pro- and anti-inflammatory cytokines in patients with unipolar and bipolar depression

Background: Immune system dysregulation is critical in the physiopathology of major depressive disorder (MDD) and bipolar disorder (BD). However, it is unclear whether both diseases present the same inflammatory patterns during depressive episodes. We explored the differences in pro-and anti-inflammatory cytokines between unipolar and bipolar depression (BDD) and the trajectory of these cytokines after acute-phase treatment. Methods: Sixty-four MDD patients, 61 BDD patients, and 62 healthy controls (HCs) were enrolled. We assessed the clinical features and cytokines plasma levels at baseline and week 12. The pro-inflammatory cytokines (IL-6, TNF-alpha) and anti-inflammatory cytokines (IL-4, IL-13) of all subjects were assessed by multiplexed sandwich ELISA-based quantitative arrays. Results: Before acute-phase treatment, the initial levels of TNF-alpha and IL-13 were significantly lower in the BDD patients than in the MDD patients. The results demonstrated that there was no relationship between each cytokine level and clinical features of unipolar and bipolar depressions. After 12 weeks, TNF-alpha, IL-4, and IL-13 levels became lower in MDD patients than in the other two groups regardless of the patients' response to treatment while the levels of TNF-alpha and IL-4 increased only in the BDD responders. Limitations: The effects of different drugs on inflammatory cytokines in MDD or BDD could not be explored further due to the relatively small sample size. Conclusion: Even within the same depressive states, MDD and BDD patients present different inflammatory features, particularly in regard to pro-inflammatory TNF-alpha and anti-inflammatory IL-13. In addition, the fluctuations of cytokines induced by medication may provide a hint regarding the prediction of treatment response.