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The Top 10 BrainImmune Updates and Why These Stories Are Fundamentally and Clinically Important

The Top 10 BrainImmune updates
The Top 10 BrainImmune Updates

If you are passionately interested and hooked to inter-disciplinary and integrative medical research, take a look below at our selection of the Top 10 Brainimmune Updates. And perhaps why these stories may be fundamentally and clinically important.

BrainImmune was conceived at the National Institutes of Health (NIH), Bethesda, MD and the decision was made at a Functional Medicine meeting in Palm Springs, CA; but it was ‘born’ in 2009, in Rome, Italy. BrainImmune is the only web resource that delivers up to date information into the broad inter-disciplinary area of neuroendocrine-immunology and stress-immune interactions, and their impact on health and disease

One of the paradoxes of medical sciences is building boundaries between disciplines and drawing dividing lines between research fields. By NARROWING DOWN the information and conceptual gap at the interface of neurosciences and immunology, OUR MISSION is to help boost and expedite the advancement of neuroendocrine immunology research.

The more we share knowledge, the easier it is to break down barriers between scientific areas.

In the first couple of years we focussed on getting published our first reviews and articles written by some of the most established experts in the field. This includes  Walter Cannon: Homeostasis, the Fight-or-Flight Response, and the Wisdom of the Body, The Discovery of Interferon by Alick Isaacs and Jean Lindenmann,  The Discovery of Adrenaline or Claude Bernard, the Father of Modern Physiology and Experimental Medicine etc.

Or strictly fundamentally- and clinically-relevant articles such as Innervation of the Human Thymus and Spleen or Influence of the Sympathetic Nervous System on Regulatory T cells, Pregnancy and Rheumatoid Arthritis, Stress Response in Childhood Asthma or Pro- and Anti-Inflammatory Effects of Stress in the Brain: Mechanisms and Implications etc.

From 2011 we started to publish short news and what’s hot or blog stories, with the idea to spread the word about some innovative and advanced research in the field. The selected updates are from these sections.

As some of these stories were published more than 10 years ago, naturally the question of bringing updates was raised for discussion. The time frame and recent Google SEO-related demands convinced us that we should proceed. Strictly scientifically, we wanted to find out if a story and research concept written and developed 10 years ago is still relevant nowadays.

And last but not least,

are these stories still fundamentally and clinically important today?

First, most of these stories reflect an innovative, advanced, stimulating etc. research, niche, or conceptual framework of the new and rapidly developing inter-disciplinary area of neuroendocrine-immunology and stress-immune interactions. Second, you will find for yourself several reasons these stories to be included here – in the discussion section(s) of the articles. And third, we will provide, and make an attempt to highlight some of the most important fundamental and clinical implications.

Thus, here’s a look at our selection of the Top 10 Brainimmune Updates:

CARDIOVASCULAR & ATHEROSCLEROSIS RESEARCH

  1. C. pneumoniae PLD and Th17 inflammation in atherosclerosis

Major story – a PNAS article indicating that Chlamydophila pneumoniae phospholipase D (CpPLD) is a major C. pneumoniae factor able to induce T helper 17 (Th17) cells’ immune response in atherosclerosis.

Chlamydophila pneumonia Th17Figure with the summary of the putative protective and pathogenic effects of IL-17 in atherosclerosis. From: IL-17 and Th17 Cells in Atherosclerosis by S. Taleb, A. Tedgui and Z. Mallat; Arterioscler Thromb Vasc Biol, 2015 Feb;35(2):258-64. Public domain.

Perhaps the first study to suggest that CpPLD is driving Th17 inflammation within the atherosclerotic plaque, and that the CpPLD-related Th17 pathway may represent a new therapeutic target for the prevention and/or treatment of atherosclerosis.

  1. Interleukin-6 – a Better Predictor of Future Cardiovascular Events

One of the paradigm shifts in our understanding about atherosclerosis in the last 10-15 years is the development of the concept that it is potentially caused by a chronic inflammation.

Serum interleukin-6 (IL-6) – as a significant predictor of future cardiovascular (CV) events, discussed in several studies; why serum IL-6, but not CRP may be a significant predictor of CV events.

IL-6 should be preferred over CRP to evaluate critically ill patients’ prognoses and possibly to guide potential therapeutic interventions aimed at taming inflammation.

NEUROENDOCRINE IMMUNOLOGY OF CANCER

  1. Autonomic Nerves and Prostate Cancer Development

Major story – a Science magazine article providing evidence that autonomic nerves contribute to prostate cancer development, where the sympathetic nervous system via the activation of β2 and β3-adrenergic receptor pathways participate in the early phase of tumor development.

The authors conclude that autonomic nerves infiltrate the prostatic tumor, and sympathetic/noradrenergic fibers are implicated in the initial stages of tumor development. The study sheds light on the exciting potential of using already available and widely used therapeutics such as beta-blockers to impact cancer prognosis.

  1. Cold Stress Linked to Immunosuppression and Increased Tumor Growth

Major story – a PNAS article demonstrates that a cool ambient housing temperature may affect the outcome of a broad range of experimental endpoints, including antitumor immunity and experimental tumor growth in mice.

  1. Stress and Suppressor Cells in Breast Cancer

Several studies indicating that chronic psychosocial stress in mice not only increases the number of myeloid-derived suppressor cells (MDSC) and Treg cells, but in the case of MDSC, also enhances their suppressive capacity.

stress MDSCFigure: Chronic stress causes the sympathetic nerve to release norepinephrine (NE). High levels of NE induce tumor cells to secrete large amount of IL-6 through β2-adrenergic receptor signal pathway. IL-6 promotes MDSCs differentiation by activating IL-6/STAT3 signal pathway. Increased MDSCs promotes lung metastasis of breast cancer. From: Chronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signalling, by Jiale an et al. Oncoimmunology, 2021 Nov 23;10. Open Access. Public Domain.

Of note, MDSCs

may represent a key link between chronic stress and tumor progression since many proinflammatory cytokines induced by chronic stress are associated with the generation and/or expansion of MDSCs.

  1. Breast cancer survivors consider stress as major factor for their disease

According to a report and survey published in Psychooncology a substantial part of women who had survived breast cancer believe that there is a link between breast cancer and psychological stress. As per another, 2018 study discussed here – salient Life Events (LEs) differentially influence breast cancer risk according to stress perception – negative valence, cumulative LEs perceived as stressful seem to be most influential in increasing breast cancer risk.

NEUROENDOCRINE IMMUNOLOGY OF AUTOIMMUNITY & CHRONIC INFLAMMATION

  1. Chronic Stress Promoting Autoimmunity via Glucocorticoid Resistance

Major story – a European Journal of Immunology article linking chronic stress and autoimmunity through a mechanism referred to as glucocorticoid resistance. This is also substantiated by a 2012 study, discussed here, indicating that chronic stress may induce glucocorticoid receptor resistance (GCR), which in turn, interferes with appropriate regulation of inflammation.

  1. Sensory Nerves Driving Interleukin-23 Production in Skin: A Breakthrough in Psoriasis Research?

Major story – a study published in the June 05, 2014 issue of Nature magazine indicates that sensory nerves driving interleukin-23 (IL-23) production by dermal dendritic cells (DDCs) may contribute to psoriasis-like inflammation. These findings may represent a breakthrough in psoriasis research and the understanding of the pathogenesis of this skin disease.

NEUROENDOCRINE IMMUNOLOGY OF MAJOR DEPRESSION

  1. Magnified IL-6 Response Linked to Stress Susceptibility & Higher Risk of Depression

Major story – a study published in the Proceedings of the National Academy of Sciences of the USA (PNAS) is perhaps the first to demonstrate that the magnitude of peripheral interleukin (IL)-6 responses preceding stress challenge may confer inter-individual differences in susceptibility or resilience to a subsequent social stressor.

The authors conclude that individual differences in the sensitivity of some peripheral immune cells, and more specifically, their IL-6 hyper-responsiveness are pre-existing and may determine a greater risk of developing a stress-related disorder, such as depression in a subgroup of susceptible individuals.

  1. A Deficit of Oxytocin in Women with Major Depression

Major story – A study published in the Journal of Psychiatric Research extends the results of two previous studies and provides evidence for a deficit of oxytocin in women with depression, including patients with psychotic major depression (PMD), who typically exhibit greater depressive severity.

Figure 1 low oxytocinFigure 1. From ‘Depressive symptomatology, temperament and oxytocin serum levels in a sample of healthy female university students’ by L. Veiga et al. BMC Psychology volume 10, Article number: 36, 2022. Open Access, Public Domain.

In addition, the study suggests that oxytocin levels may also be linked to desirability, drug dependence, and compulsivity scores as measured by the Million Clinical Multiaxial Inventory-III.

Ilia Elenkov, MD, PhD
The Editors, BrainImmune: Trends in Neuroendocrine Immunology

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