Decreased hydrocortisone sensitivity of T cell function in multiple sclerosis-associated major depression

Psychoneuroendocrinology. 2012 Oct;37(10):1712-8. doi: 10.1016/j.psyneuen.2012.03.001. Epub 2012 Mar 27.

Abstract

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS with a high prevalence of depression. Both MS and depression have been linked to elevated cortisol levels and inflammation, indicating disturbed endocrine-immune regulation. An imbalance in mineralocorticoid versus glucocorticoid signaling in the CNS has been proposed as a pathogenetic mechanism of depression. Intriguingly, both receptors are also expressed in lymphocytes, but their role for 'escape' of the immune system from endocrine control is unknown. Using steroid sensitivity of T cell function as a read-out system, we here investigate a potential role of mineralocorticoid receptor (MR) versus glucocorticoid receptor (GR) regulation in the immune system as a biological mechanism underlying MS-associated major depression. Twelve female MS patients meeting diagnostic criteria for current major depressive disorder (MDD) were compared to twelve carefully matched MS patients without depression. We performed lymphocyte phenotyping by flow cytometry. In addition, steroid sensitivity of T cell proliferation was tested using hydrocortisone as well as MR (aldosterone) and GR (dexamethasone) agonists. Sensitivity to hydrocortisone was decreased in T cells from depressed MS patients. Experiments with agonists suggested disturbed MR regulation, but intact GR function. Importantly, there were no differences in lymphocyte composition and frequency of T cell subsets, indicating that the differences in steroid sensitivity are unlikely to be secondary to shifts in the immune compartment. To our knowledge, this study provides first evidence for altered steroid sensitivity of T cells from MS patients with comorbid MDD possibly due to MR dysregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aldosterone / agonists
  • Aldosterone / pharmacology
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Depressive Disorder, Major / drug therapy*
  • Dexamethasone / agonists
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Flow Cytometry
  • Humans
  • Hydrocortisone / agonists
  • Hydrocortisone / pharmacology*
  • Immunophenotyping
  • Multiple Sclerosis / drug therapy*
  • T-Lymphocytes / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Aldosterone
  • Dexamethasone
  • Hydrocortisone