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.