Th1, Th2, and Th3 cytokine alterations in major depression

J Affect Disord. 2005 Oct;88(2):167-73. doi: 10.1016/j.jad.2005.07.008.


Background: Many studies have shown that the balance between Th1 cytokines and Th2 cytokines plays a role in modulation of cellular responses in the brain during psychological stress and psychiatric disorders. The Th3 cytokine, transforming growth factor beta-1 (TGF-beta1), has been shown to regulate the balance between Th-1 and Th-2 cytokines. However, the role of TGF-beta1 in the psychoimmunology of depression has never been explored.

Methods: A total of 40 depressed patients and 80 normal controls were recruited. The plasma levels of IFN-gamma, IL-4, and TGF-beta1 were studied at the time of admission and 8 weeks after antidepressant treatment.

Results: The proportion of patients who showed immunoreactivity to IFN-gamma and IL-4 in the plasma, and the plasma IFN-gamma/IL-4 ratio, were significantly higher in depressed patients than in controls. The IFN-gamma/TGF-beta1 ratio was also higher in depressed patients, and TGF-beta1 levels showed a significant negative correlation with the HDRS depression scale. After treatment, TGF-beta1 level increased significantly, and the IFN-gamma/IL-4 ratio decreased significantly, in the patient group. However, Th1 changes in male and female showed different trend such as Th1 arm was decreased after the treatment in all male, whereas it was increased in premenopausal age women.

Limitations: Replication and extension using a larger sample size are required.

Conclusions: The Th1 and Th2 cytokine imbalance was observed in subpopulation of depressed patients. TGF-beta1 seemed to play a role in the pathophysiology of depression in this population. Moreover, antidepressant treatment was found to affect the Th1/Th2 balance through the action of TGF-beta1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use
  • Brain / metabolism*
  • Brief Psychiatric Rating Scale
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / metabolism*
  • Depressive Disorder, Major / physiopathology
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interleukin-4 / blood
  • Lymphotoxin-alpha / blood
  • Male
  • Mental Disorders / metabolism
  • Mental Disorders / psychology
  • Stress, Psychological / metabolism
  • Stress, Psychological / psychology
  • T-Lymphocytes, Regulatory / metabolism*
  • Th1 Cells / metabolism*
  • Th2 Cells / metabolism*
  • Time Factors


  • Antidepressive Agents
  • Lymphotoxin-alpha
  • Interleukin-4
  • Interferon-gamma