The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery

Psychoneuroendocrinology. 2014 Jul;45:77-86. doi: 10.1016/j.psyneuen.2014.03.019. Epub 2014 Apr 6.


Background: Cytokines are implicated in the pathophysiology of major depressive disorder (MDD). However, the pattern of alterations in cytokine levels is still unclear. The current study investigated the plasma levels of a range of cytokines in a follow-up design, with the aim of determining their involvement in depression.

Methods: Fifty medication-free MDD patients with a depressive episode and 34 healthy controls were included at baseline; the patients were followed up after 12 weeks. Before initiating treatment, the patients were diagnosed and assessed for depressive symptoms and blood for cytokine analysis was obtained. The same clinical assessments and cytokine measurements were performed after 12 weeks of "treatment as usual."

Results: The cytokines interleukin (IL)-1β, IL-1 receptor antagonist (IL-1Ra), IL-5, IL-6, IL-7, IL-8, IL-10, granulocyte colony-stimulating factor (G-CSF), and interferon gamma (IFNγ) were significantly elevated (p=0.01-0.047) in depressed patients at baseline compared to healthy controls. After 12 weeks of treatment, the plasma levels of seven of these nine cytokines (IL-1Ra, IL-6, IL-7, IL-8, IL-10, G-CSF, and IFNγ had decreased significantly compared to baseline and did not differ from those in the healthy controls. The depressive symptoms were simultaneously significantly reduced. In addition, the reduction to normal cytokines levels occurred only in those who met the recovery criteria.

Conclusion: A more general pattern of elevated cytokine levels is described herein relative to what has been described previously shown in MDD. Furthermore, recovery from depression was associated with reduction to normal levels of the majority of the measured cytokines. These results strongly support the notion that a complex network of cytokines is involved in the pathophysiology of MDD.

Keywords: Anti-inflammatory cytokines; Cytokine pattern; Follow-up; Major depressive disorder; Proinflammatory cytokines; Recovery; Th1 cytokines; Th2 cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use
  • Case-Control Studies
  • Cytokines / blood*
  • Depressive Disorder, Major / blood*
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / rehabilitation*
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Recovery of Function / physiology*
  • Severity of Illness Index
  • Treatment Outcome
  • Up-Regulation


  • Antidepressive Agents
  • Cytokines
  • Inflammation Mediators