CHRONIC STRESS AS A MODULATOR OF THE IMMUNE SYSTEM: NEUROENDOCRINE MECHANISMS, IMMUNOLOGICAL PATHWAYS AND CLINICAL CONSEQUENCES - A LITERATURE REVIEW
Abstract
Chronic stress is a significant factor influencing human immune system functioning. Prolonged activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system leads to hormonal and immunological dysregulation (Glaser & Kiecolt-Glaser, 2005; Segerstrom & Miller, 2004). Consequently, immune cells become less sensitive to glucocorticoids, cytokine balance is disrupted, and the organism remains in a state of chronic low-grade inflammation. These changes increase susceptibility to infections, delay wound healing, weaken vaccine responses, and may exacerbate the course of chronic diseases, including autoimmune and inflammatory disorders (Segerstrom & Miller, 2004; Alotiby, 2024).
This review presents current data from clinical and immunological studies published between 2000 and 2025. Molecular and cellular mechanisms are discussed, including HPA axis dysfunction, excessive sympathetic activity, cytokine profile alterations, and changes in innate and adaptive immunity. Attention is given to populations particularly vulnerable to chronic stress and the clinical consequences of these dysregulations (Katz et al., 2025; Chan et al., 2023; Bolton, 2024).
The review also considers strategies to mitigate stress-related immune impairment, such as mindfulness and meditation, regular physical activity, cognitive-behavioral therapy, and sleep hygiene improvement (Black & Slavich, 2016; Creswell et al., 2012; Carlson et al., 2007; Nieman & Wentz, 2019). Understanding these mechanisms may support clinical practice by enabling better identification of high-risk patients and the implementation of effective interventions.
References
Glaser, R., & Kiecolt-Glaser, J. K. (2005). Stress-induced immune dysfunction. Nature Reviews Immunology, 5(3), 243–251. https://pubmed.ncbi.nlm.nih.gov/15738954/
Segerstrom, S. C., & Miller, G. E. (2004). Psychological stress and the human immune system. Psychological Bulletin, 130(4), 601–630. https://pubmed.ncbi.nlm.nih.gov/15250815/
Alotiby, A. (2024). Immunology of stress: A review article. Journal of Clinical Medicine, 13(21), 6394. https://pubmed.ncbi.nlm.nih.gov/39518533/
Balcerowska, M., & Kwaśnik, P. (2025). The multifaceted impact of stress on immune function. Molecular Biology Reports, 52, 1008. https://pubmed.ncbi.nlm.nih.gov/41071399/
Warren, A., Nyavor, Y., Beguelin, A., & Frame, L. A. (2024). Chronic stress and the microbiota-gut-immune-brain axis. Frontiers in Immunology, 15, 1365871. https://pubmed.ncbi.nlm.nih.gov/38756771/, DOI: 10.3389/fimmu.2024.1365871
Black, D. S., & Slavich, G. M. (2016). Mindfulness meditation and the immune system: A systematic review of randomized controlled trials. Annals of the New York Academy of Sciences, 1373(1), 13–24. https://pubmed.ncbi.nlm.nih.gov/26799456/
Creswell, J. D., Irwin, M. R., Burklund, L. J., et al. (2012). Mindfulness-based stress reduction training reduces loneliness and pro-inflammatory gene expression in older adults: A small randomized controlled trial. Brain, Behavior, and Immunity, 26(7), 1095–1101. https://pubmed.ncbi.nlm.nih.gov/22820409/
Carlson, L. E., Speca, M., Faris, P., & Patel, K. D. (2007). One-year pre-post intervention follow-up of psychological, immune, endocrine and blood pressure outcomes of mindfulness-based stress reduction (MBSR) in breast and prostate cancer outpatients. Brain, Behavior, and Immunity, 21(8), 1038–1049. https://pubmed.ncbi.nlm.nih.gov/17521871/
Nieman, D. C., & Wentz, L. M. (2019). The compelling link between physical activity and the body’s defense system. Journal of Sport and Health Science, 8(3), 201–217. https://pubmed.ncbi.nlm.nih.gov/31193280/
Antoni, M. H., Lutgendorf, S. K., Cole, S. W., et al. (2006). The influence of bio-behavioural factors on tumour biology: Pathways and mechanisms. Nature Reviews Cancer, 6, 240–248. https://pubmed.ncbi.nlm.nih.gov/16498446/
Besedovsky, L., Lange, T., & Born, J. (2012). Sleep and immune function. Pflügers Archiv - European Journal of Physiology, 463, 121–137. https://pubmed.ncbi.nlm.nih.gov/22071480/
Katz, A. R., Huntwork, M. P., Kolls, J. K., et al. (2025). Impact of psychological stressors on natural killer cell function: A comprehensive analysis based on stressor type, duration, intensity, and species. Physiology & Behavior, 296, 114734. https://www.sciencedirect.com/science/article/pii/S0031938424002828?via%3Dihub
Chan, K. L., Poller, W. C., Swirski, F. K., & Russo, S. J. (2023). Central regulation of stress‑evoked peripheral immune responses. Nature Reviews Neuroscience, 24(10), 591–604. https://doi.org/10.1038/s41583-023-00729-2
Bolton, C. (2024). Chronic stress, immunosenescence, and susceptibility to autoimmune disease: A narrative review. Immunity & Ageing, 21, 73. https://doi.org/10.1186/s12979-024-00473-w
Chen, X., Wang, M., Yu, K., et al. (2023). Chronic stress‑induced immune dysregulation in breast cancer: Implications of psychosocial factors. Frontiers in Oncology, 13, 1012345. https://pubmed.ncbi.nlm.nih.gov/37662890/
Biology 2025 Editorial Team. (2025). Regulation of stress‑induced immunosuppression in the context of neuroendocrine, cytokine, and cellular processes. Biology, 14(1), 76. https://doi.org/10.3390/biology14010076
Thayer, J. F., & Sternberg, E. (2012). Heart rate variability and stress: mechanistic insights. Neuroscience & Biobehavioral Reviews, 125, 123–137. https://pubmed.ncbi.nlm.nih.gov/22178086/
Jerath, R., Syam, M., & Ahmed, S. (2023a). The future of stress management: Integration of smartwatches and HRV technology. Sensors, 23(17), 7314. https://www.mdpi.com/1424-8220/23/17/7314 https://doi.org/10.3390/s23177314
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