Journal Nature confirmed the negative role of acute stress on Immunity

--potential role of acupuncture?


Manuscript Title: Brain motor and fear circuits regulate leukocytes during acute stress Journal: Nature – Embargo Lifts May 30, 11am EST Corresponding Author: Filip Swirski, PhD, Director of the Cardiovascular Research Institute at the Icahn School of Medicine at Mount Sinai Bottom Line: Acute stress can be detrimental to fighting off infection, especially COVID-19, and increases the chance of dying in mouse models.


With the ever-accelerating pace of modern life and work, people are experiencing more stress than ever before, and stressful modern people are also facing more and more health challenges. In previous studies, scientists have confirmed that stress can increase the occurrence and development of various diseases (including emotional disorders and post-traumatic stress disorder, obesity, diabetes, tumors, etc.). In the stress response, there is a close dialogue and connection between the nervous system and the immune system. Studies have found that stress response is an important factor affecting immune function, but whether there is a direct relationship between stress in the brain and peripheral blood leukocytes and what kind of connection exists is still poorly understood.


This study showed that under acute stress conditions, white blood cells, including neutrophils, monocytes, B cells and T cells, undergo significant changes in tissue distribution in mice. Different brain regions rapidly adjust the distribution of white blood cells in different ways, thereby adjusting the responsiveness of the body's immune system. The researchers further demonstrated that acute stress alleviated autoimmune encephalomyelitis (EAE) in mice, but aggravated infections caused by SARS-CoV-2 and influenza viruses. This important finding sheds light on the regulation of the immune system by different brain regions and neural circuits under stressful conditions, and also elucidates the impact of stress on the development of different inflammatory diseases, with potential clinical implications.


This study is the first to show how specific regions in the brain control the body’s cellular immune response while under acute stress and infected with COVID-19 or influenza. More specifically, it demonstrated that acute stress prompts neurons from the region known as the paraventricular hypothalamus to instantly trigger a large-scale migration of white blood cells (immune cells, or leukocytes) from lymph nodes to the blood and bone marrow. This diminishes an immune response to viruses such as COVID-19 and influenza, making the body less resistant to fighting infection and putting it at greater risk of complications and death.


Why this is important: This fundamental discovery connecting the brain to the immune system provides a better understanding of how stress affects the body’s response to a virus, and why some may be more susceptible to severe illness and worse outcomes.


Fig. 1: Acute stress impairs the acquisition of immunity to SARS-CoV-2 and influenza

a, Experimental schematic. b, Lymphocytes in lymph nodes (n=4-5 per group). c, Pulmonary viral loads (n=5 per group). d, Survival curves (n=12 non-stressed, n=14 stressed; two experiments). Log-rank (Mantel-Cox) test. e-k, Mice infected with sublethal dose of influenza A virus (IAV). e, Experimental schematic f, Images of mediastinal lymph nodes g, B cells in mediastinal lymph node of WT, PVH-CRH neuron ablated, and B cell specific GR-KO mice, as well as of mice with chemogenetic PVH-CRH neuron stimulation (dark orange) or vehicle injection (light orange) (n=7-12 per group). h, T cells in mediastinal lymph nodes in mice as above and indicated, except for T cell specific GR-KO (n=7-12 per group). i, j, IAV-specific IgG in the BAL (i) and pulmonary viral loads (j) of mice as above and indicated (n=7-12 per group), two-tailed unpaired t-test, Mann-Whitney test). k, H&E-stained lung cross-sections of mice under indicated conditions. Scale bar: 1 mm in low-magnification, 41 µm in high-magnification.

Data are mean ±s.e.m.; ★P<0.05, ★★P<0.01, ★★★ P<0.001, statistical tests: two-tailed unpaired t test in b,c,g,h,i; otherwise indicated.


Potential role of acupuncture


As one important part of body-mind medicine, acupuncture has been applied to a variety of mental disorders such as depression, anxiety, bipolar disease, post-traumatic stress disorders. Also in Traditional Chinese Medicine, stress is always an important cause of chronic disorders, with unclear mechanism. This study showed that acute stress may be detrimental to fighting off COVID-19 and influenza. Formal studies also confirmed that stimulating ST36 (zusanli) is helpful in alleviating inflammatory response of COVID-19. We wish more studies will be published to elucidate how chronic stress affects long-term health.


References:


1. Brain motor and fear circuits regulate leukocytes during acute stress. Nature. https://www.nature.com/articles/s41586-022-04890-z_reference.pdf

2. Acute stress may be detrimental to fighting off COVID-19 and influenza. https://www.eurekalert.org/news-releases/954163

3. A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis. Nature. https://pubmed.ncbi.nlm.nih.gov/34646018/

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