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The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X
Abstract
In previous publications, we presented the hypothesis that repeated episodes of acute or chronic psychological stress could induce an acute phase response (APR) and subsequently a chronic inflammatory process such as atherosclerosis. In this paper, that hypothesis, namely that such stress can induce an APR and inflammation, has been extended to include a chronic inflammatory process(s), characterized by the presence of certain cytokines and acute phase reactants (APR), which is associated with certain metabolic diseases. The loci of origin of these cytokines, particularly interleukin 6 (IL-6), and their induction, has been considered. Evidence is presented that the liver, the endothelium, and fat cell depots are the primary sources of cytokines, particularly IL-6, and that IL-6 and the acute phase protein (APP), C-reactive protein (CRP), are strongly associated with, and likely play a dominant role in, the development of this inflammatory process which leads to insulin resistance, non-insulin dependent diabetes mellitus type II, and Metabolic syndrome X. The possible role of psychological stress and the major stress-related hormones as etiologic factors in the pathogenesis of these metabolic diseases, as well as atherosclerosis, is discussed. The fact that stress can activate an APR, which is part of the innate immune inflammatory response, is evidence that the inflammatory response is contained within the stress response or that stress can induce an inflammatory response. The evidence that the stress, inflammatory, and immune systems all evolved from a single cell, the phagocyte, is further evidence for their intimate relationship which almost certainly was maintained throughout evolution.
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“Inflammation is associated with autonomic dysfunction (Black, 2003; McGovern and Mazzone, 2014; Mirakaj et al., 2014), so this result is compatible with the hypothesis that the reduction in hs-CRP may be due in part to improved autonomic function.”
From Effectiveness of a Novel Qigong Meditative Movement Practice for Impaired Health in Flight Attendants Exposed to Second-Hand Cigarette Smoke (2017) · cites this paper as Black, 2003
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Rowley, K., & Anderson, I. P. S. (2006) · Internal Medicine Journal · doi:10.1111/j.1445-5994.2006.01233.x · Cited by 3
Yu, J., Cudjoe, T., Mathis, W. S., & Chen, X. (2025) · The Journals of Gerontology Series B · doi:10.1093/geronb/gbaf242 · Cited by 2
Sabry, M. O., Seleem, M. M., Ebrahim, Y. M., Hussien, S. G., Ahmed, R., Hassan, H. E., Bahr, A., Alsadany, M. A., El-Shiekh, R. A., & Ali, D. E. (2025) · Revista Brasileira de Farmacognosia · doi:10.1007/s43450-025-00729-6 · Cited by 2
Metadata
- Authors
- Black, P. H.
- Affiliations
- Boston University (US)
- Corresponding author
- Black, Paul H.
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 17
- Issue
- 5
- Pages
- 350-364
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2081378977
- Cited by
- 502
- References
- 148
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 16 · 2023: 15 · 2022: 22 · 2021: 14 · 2020: 20 · 2019: 21 · 2018: 19 · 2017: 26 · 2016: 18 · 2015: 31 · 2014: 22 · 2013: 25 · 2012: 36
- FWCI
- 15.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- psychological stress, inflammation, acute phase response, atherosclerosis, insulin resistance, type 2 diabetes, metabolic syndrome X, interleukin-6, C-reactive protein, cytokines, acute phase proteins, innate immunity, stress hormones, liver, endothelium, adipose tissue, immune system evolution
- MeSH terms
- Acute-Phase Reaction, Arteriosclerosis, Diabetes Mellitus, Type 2, Humans, Inflammation, Insulin Resistance, Obesity, Stress, Physiological, Stress, Psychological, Interleukin-6, Metabolic Syndrome
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