key: cord-0884351-o6zov8rq authors: Theoharides, Theoharis C. title: Stress, Inflammation and Autoimmunity: The Three Modern Erinyes date: 2020-04-18 journal: Clin Ther DOI: 10.1016/j.clinthera.2020.04.002 sha: 301a559e833551f0b7500a523f3bcc20744feaee doc_id: 884351 cord_uid: o6zov8rq nan There is no more relevant time to be addressing the effect of stress as the health, economic and emotional stressors associated with COVID-19 have engulfed the entire planet. 1 Stress has been particularly apparent among health care workers who are more exposed and susceptible to infection, as well as to the emotional strain of caring for SARS-CoV-2 patients. 2 Stress, inflammation and autoimmunity may stand for the Erinyes of modern times. In ancient Greek mythology, the Erinyes, also known as the Furies, were female chthonic deities of vengeance, especially for crimes committed against the natural world order. 3 The first mention of stress possibly contributing to disease pathology was by Hippocrates, who advised a patient with asthma to contain his anger that he felt contributed to his condition. 4 Mounting evidence has shown that stress 5,6 adversely affects many different diseases, especially autoimmune, 7,8 and inflammatory 9,10 disorders, such as aging, 11 allergies, 12, 13 Alzheimer's disease, 14 23 and myalgic encephalomyelitis/chronic fatigue syndrome. 24 Stress typically activates the hypothalamic-pituitary-adrenal (HPA) axis, the "fight or flight" system developed to ensure the survival of the organism, via release of catecholamines and corticosteroids from the adrenal glands. Acute stress increases the readiness of the organism and typically decreases the function of the immune system. In contrast, prolonged stress has the opposite effect contributing to chronic inflammation, 25 either via blunting the cortisol effect and/or activation of the tissue immune cells, the mast cells. 26 Mast cells contribute to both health and disease. 27, 28 Mast cells are located around blood vessels and nerves in all tissues, including the brain, acting as sensors of environmental and pathogenic "danger" signals, 29 by secreting multiple pro-inflammatory mediators. 30, 31 Mast cells may mediate the pro-inflammatory effect of stress in response to stimulation by neurohormonal triggers, 32 especially the key stress mediator corticotropin-releasing hormone (CRH). 33 In fact, CRH stimulates mast cells and is also synthesized by mast cells. 34 In this May issue, part one of the Stress and Immunity Update emphasizes the effect of stress on skin immune processes. [35] [36] [37] [38] Scientists address the effect of stress on itch and chronic urticaria, as well as the effect of stress on levels of immune molecules and neurotransmitters. The June issue will focus on the effects of acute and chronic stress on neuroimmune processes and the reprogramming of the immune system. Vicarious traumatization in the general public, members, and nonmembers of medical teams aiding in COVID-19 control Mental health care for medical staff in China during the COVID-19 outbreak Stress and Asthma: Hippocrates Revisited The legacy of Hans Selye and the origins of stress research: a retrospective 75 years after his landmark brief "letter" to the editor of nature Stress, chronic inflammation, and emotional and physical well-being: concurrent effects and chronic sequelae Environmental and occupational stress and autoimmunity Cumulative childhood stress and autoimmune diseases in adults The stress response and the regulation of inflammatory disease Critical role of mast cells in inflammatory diseases and the effect of acute stress The role of stress factors during aging of the immune system Stress, mindfulness, and the allergic patient Perceived stress predicts allergy flares Mast cells in stress, pain, Blood-Brain Barrier, neuroinflammation and Alzheimer's disease. Front Cell Neurosci Contribution of stress to asthma worsening through mast cell activation The role of stress in asthma: insight from studies on the effect of acute and chronic stressors in models of airway inflammation Mast Cells, Stress, Fear and Autism Spectrum Disorder Effects of mycotoxins on neuropsychiatric ymptoms and immune processes The impact of psychosocial stress and stress management on immune responses in patients with cancer. Cancer Impact of stress and mast cells on brain metastases Stress triggers coronary mast cells leading to cardiac events Psychological stress, inflammation, and Coronary Heart Disease Effect of stress on brain inflammation and multiple sclerosis A Timely multidisciplinary update on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation Mast cells, mastocytosis, and related disorders Mast cells as drivers of disease and therapeutic targets Mast cells signal their importance in health and disease Danger signals and inflammation Mast cells and inflammation Mast cells as sources of cytokines, chemokines, and growth factors Neuroendocrinology of mast cells: Challenges and controversies Key role of CRF in the skin stress response system Mast cells as targets of corticotropin-releasing factor and related peptides Stress-induced interaction of skin immune cells, hormones, and neurotransmitters The effects of stress on itch