Cytokine levels in euthymic bipolar patients

J Affect Disord. 2010 Nov;126(3):458-62. doi: 10.1016/j.jad.2010.04.027.


Background: The pathophysiology of bipolar disorder is not thoroughly understood. Several studies have investigated the possible role of cytokines in psychiatric disorders, based on their role in neuro-immune modulation; however, findings in studies on bipolar disorder remain limited and contradictory, and most studies have focused on either manic or depressive episodes. These studies suggest that both manic and depressive episodes could be pro-inflammatory states. The present study aimed to determine whether there are enduring differences in cytokine levels-unrelated to the effects of medication-between euthymic bipolar patients and healthy controls.

Methods: The study included 31 euthymic bipolar patients-16 medication-free (MF) and 15 on lithium monotherapy (LM) and 16 healthy volunteers in whom serum cytokine levels were measured. The 3 groups were homogenous in terms of age, gender, and ethnicity. IFN-γ, TNF-α, IL-2, IL-4, IL-5, and IL-10 levels were measured in all groups using flow cytometry.

Results: There were no differences in cytokine levels between MF euthymic bipolar patients and healthy controls. TNF-α and IL-4 levels in LM euthymic bipolar patients were higher than in both the MF euthymic bipolar patients and controls.

Limitations: The small and strictly selected study sample could limit the generalizability of the findings.

Conclusions: Cytokine production in MF euthymic bipolar patients was similar to that in healthy controls. The present study shows that the pro-inflammatory state resolves in euthymia and that lithium had an influence on the cytokine profile, which could create a confounding factor while investigating disease- related immunopathology of bipolar disorder.

MeSH terms

  • Adult
  • Bipolar Disorder / immunology*
  • Bipolar Disorder / psychology
  • Cytokines / blood*
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-2 / blood
  • Interleukin-4 / blood
  • Interleukin-5 / blood
  • Male
  • Reference Values
  • Tumor Necrosis Factor-alpha / blood


  • Cytokines
  • Interleukin-2
  • Interleukin-5
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma