The role of stress-response systems for the pathogenesis and progression of MS

Trends Immunol. 2005 Dec;26(12):644-52. doi: 10.1016/ Epub 2005 Oct 7.


Disease progression in multiple sclerosis (MS)--an inflammatory demyelinating and neurodegenerative disease with a presumed T-cell driven autoimmune origin--has long been hypothesized to be associated with stress. However, this notion has only recently been supported by prospective clinical studies. Several clinical and molecular studies in MS and its animal models have recently shown disruptions in the communication between the immune system and the two major stress response systems, the hypothalamo-pituitary-adrenal (HPA) axis and the autonomic nervous system. Insensitivity to glucocorticoid and beta-adrenergic modulation might be involved in overshooting inflammation in MS, whereas hyperactivity of the HPA axis has been linked to neurodegeneration and increased disability. Here, we integrate findings from molecular, cellular, experimental, clinical and epidemiological research to describe the involvement of stress response systems in MS pathogenesis and progression.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autonomic Nervous System / immunology
  • Autonomic Nervous System / pathology
  • Autonomic Nervous System / physiopathology
  • Disease Progression
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Humans
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis / physiopathology*
  • Stress, Physiological / physiopathology*