The role of stress in the mosaic of autoimmunity: An overlooked association

Autoimmun Rev. 2018 Oct;17(10):967-983. doi: 10.1016/j.autrev.2018.04.005. Epub 2018 Aug 14.


Stress is defined as the pscyophysiological reaction in which the steady state is disturbed or threatened. Stress is not always perceived as a negative response. Stress results when environmental demands exceed an individuals' adaptive capacities. Autoimmune diseases are heterogeneous group of chronic diseases which occur secondary to loss of self antigen tolerance. The etiopathogenesis of autoimmune disease is uncertain. Genetic factors as well as environmental factors appear to interplay, leading to a cascade of events resulting in disease onset. Stress has been postulated to play a role in disease onset in the genetically susceptible patients. During the stress response, catecholamines and glucocorticoids are released from locus coeruleus and adrenal gland. These biomolecules exert control over various immune cells in the innate and adaptive arms of the immune system, thereby altering the cytokine profile released. The increase of IL-4 promotes T-helper 2 (Th2) cell differentiation, while the decrease in IL-12 and the increased IL-10 production reduce the number of T-helper 1 (Th1) cells. The relationship between stress and autoimmune diseases is intricate. Stress has been shown to be associated with disease onset, and disease exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune conditions. In certain conditions such as psoriasis, stress has been implicated in delaying lesion clearance upon the application of standard treatment regimes. Finally, psychological therapy and cognitive behavioral therapy aimed to reduce stress levels was shown to be effective in influencing better outcomes in many autoimmune diseases. The purpose of this paper is to closer inspect the clinical evidence regarding the role of stress on influencing the various aspects of disease entities.

Keywords: Autoimmune diseases; Autoimmunity; Glucocorticoids; Rheumatoid arthritis, autoantibodies; Stress.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / physiopathology*
  • Autoimmunity
  • Cytokines / immunology
  • Humans
  • Neurosecretory Systems / pathology
  • Neurosecretory Systems / physiopathology
  • Stress, Physiological*
  • Stress, Psychological*
  • T-Lymphocytes, Helper-Inducer / immunology


  • Cytokines