Chronic psychological stress mediated immune modulation induced autoimmune diseases

London Journal of Research in Science: Natural and Formal
Volume | Issue | Compilation
Authored by Shrihari T.G , NA
Classification: For Code: 170101
Keywords: HPA-axis, autoimmunity, neuropeptides, cortisol, NF-KB, Tregs.
Language: English

chronic psychological Stress is a main etiological factor for autoimmune diseases by releasing neuropeptides activates inflammatory mediators such as IL-1,TNF- α,IL-6, and COX-2 , proinflammatory cytokines induce activation of NF-KB a key transcription factor involved in chronic inflammation , immune modulation, cell proliferation, cell survival, angiogenesis, and augments autoimmunity. This article briefs about the role of chronic psychological stress mediated immune modulation induced autoimmune diseases.


Chronic Psychological Stress Mediated Immune Modulation Induced Autoimmune Diseases

Shrihari T.G



Chronic psychological Stress  is a main  etiological  factor  for autoimmune  diseases   by releasing  neuropeptides  activates inflammatory  mediators such as  IL-1,TNF-α,IL-6, and COX-2 , proinflammatory  cytokines  induce  activation of  NF-KB a key transcription factor  involved in  chronic inflammation , immune modulation, cell proliferation, cell survival, angiogenesis, and  augments    autoimmunity. This article briefs about the role of chronic psychological stress mediated immune modulation induced autoimmune diseases.

Keywords: HPA-axis, autoimmunity, neuropep-

tides, cortisol, NF-KB, Tregs.

Author: Assistant  professor, Department of Oral medicine and oral oncology, Krishna devaraya college of dental sciences and hospital, Bangalore -562157,Karnataka, India.


Chronic psychological stress, anger, hatred, depression, frustration  induced release of CRH (Corticotropin releasing hormone) from hypothalamus activate HPA-axis through ANS release neuropeptides such as cortisol, noradrenaline,  and ACTH  activates inflammatory mediators such as IL-1β,TNF-α, IL-6 and COX-2 ,which activates  NF-KB and  STAT-3 key transcription factors involved in chronic inflammation (IL-1β,TNF-α), immune modulation (IL-10,TGF-β, iNOS), tissue damage (MMP’s2,9,ROS,RNS), cell proliferation (Cyclin D,E), angiogenesis (IL-8,COX-2,VEGF), cell survival (BCL-XL,BCL-2) (1-10) . NF-KB a key transcription factor  induced expression of inflammatory mediators  such as chemokines, cytokines, growth factors , and proteolytic enzymes  involved in conversion of TH1 lymphocytic type to TH2 lymphocytic type mediated by IL-4,STAT6 transcription factor  release IL-4,IL-13,IL-5 proinflammatory cytokines along with TH17  cells  involved in chronic inflammation, immune modulation, and tissue damage. IL-1, COX-2, and TNF-α pro-inflammatory cytokines activate NF-KB a key transcription factor, IL-6, IL-10,EGF, FGF activate STAT-3 transcription factor, both transcription factors work together involved in cell proliferation by expression of cyclin D,E cell cycle regulatory proteins  and cell survival by BCL-2, BCL-XL anti-apoptotic proteins. Growth factors such as EGF, FGF, VEGF involved in cell proliferation, cell survival, and angiogenesis. Altered induced regulatory T cells (iTregs)  formed from TH1 cells mediated by TGF-β inflammatory mediator release IL-4,IL-2,IL-10IL-17,IL-13,IL-5, proinflammatory cytokines involved in immune modulation by inhibiting innate and adaptive immune cells (involved   in  decreased  mitogenic response  in lymphocytes, natural killer cell cytotoxicity is decreased , IgA secretion) ,otherwise normal  regulatory T cells (nTregs)  involved in self tolerance and immune homeostasis. Proteolytic enzymes such as matrix mettalo proteases 2,9 (MMP’S2,9) involved in tissue damage, all these changes leads to autoimmune diseases (10-20) .


  1. Silverstein AM. Autoimmunity versus horror autotoxicus: The struggle for recognition. Nature immunology 2001;2:279-281.
  2. Silverstein A. Horror autotoxicus, Autoimmunity and immunoregulation: The early history. Transfusion medicine and chemotherapy 2005;32:296-302.
  3. Silverman MN, Sternberg EM. Glucocorticoid regulation of inflammation and its behavioral and metabolic co relates: from HPA axis to glucocorticoid receptor dysfunction. Ann NyAcadsci 2012;6:55-63.
  4. Ljudmila Stojanovich. Stress and autoimmunity. Autoimmunity reviews 2010;9:271-76.
  5. Sphepshelovich D, Shoenfeld Y. Prediction and prevention of autoimmune diseases: additional  aspects of the mosaic of autoimmunity. Lupus 2006;15:183-190.
  6. Dube SA, Fairweather Del, Pearson WS, Felitti VJ, Anda RF, Croft JB. Cumulative childhood stress and autoimmune diseases in adults. Psychosom Med 2009:71:243-50.
  7. Prashant B P,Anusuya G H. Psychosomatic disorders of the oral cavity- A Review. American Journal of oral oral Medicine and Radiology 2015;2(2):96-102.
  8. Manolache L, Petrescu-Seceleanu D. Stress involvement as trigger factor in different skin conditions. World journal of dermatology 2013;2(3):16-26.
  9. Chaudhary S. Psychological stressors in oral lichen planus.Aus Dent J 2004;49(4):192-195.
  10. Satyanarayana RTS. Psychosomatic paradigms in psoriasis:psoriasis,stress and mental health. Ind J psy2013;55(4):313-15.
  11. Segerstrom SC, Miller GE. Psychological stress and human immune system. A meta-analytic study of 30 years of inquiry. Psychological Bulletin 2013;1:601-630.
  12. Stojanovich L, Marisavijevich D. Stress as a trigger of autoimmune disease. Autoimmun Rev 2008;7: 209-13.
  13. Jessop DS, Richards LJ, Harbuz MS. Effects of stress on inflammatory autoimmune disease: destructive or protective? Stress 2004:7:261-268.
  14. Shoenfeld YZ, Man-Goddard G, Stojanovich L, Cutolo M,Amital H, Ley Y, et al. The mosaic of autoimmunity: Hormonal and environmental factors involved in autoimmune diseases.IMAJ 2008;21:55-89.
  15. SapolskyRM,Romero ML, Munck AV. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 2000;21:55-89.
  16. Stojanovich L, Marisavijevich D. Stress as a trigger of autoimmune disease. Autoimmun Rev 2008;7: 209-13.
  17. Priyadarshini S, Palok A. Effects of psychological stress on innate immunity and metabolism in humans : A systematic analysis. Plos One 2012;7(9):8-15.
  18. Shrihari T.G. Chronic psychological stress induced microbial imbalance (dysbiosis) mediated autoimmune disease-A current concept. Gerontology and geriatric studies 2018;3(1):1.
  19. Shrihari T.G. Current concept of Auto-immune disease and holistic therapeutic approach. EC microbiology 2018;15(2): 103-107.
  20. Shrihari T.G. Beta-Endorphins – Therapeutic Boon. International Journal of Modern Pharmaceutical Research 2018;2(6):7-8.



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