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Immunology of Stress: A Review Article
Open accessAbstract
Stress significantly impacts the immune system, affecting susceptibility to illness and overall health. This review examines the intricate relationship between stress and the immune system, offering insights having practical implications for health and disease prevention. Stress can significantly trigger molecular and immune modulation, affecting the distribution and trafficking of immune cells in various organs and altering their composition in the blood. The review delves into two key pathways connecting stress and immunity: the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system. Stress activates the neuroendocrine system and triggers microglia in the brain, releasing stress hormones and neurotransmitters that modulate the function and movement of immune cells. Acute stress can temporarily strengthen immunity and promote protection during infection; in contrast, chronic stress dysregulates or inhibits immune functions. Chronic stress causes an increase in cortisol levels through the HPA axis, ultimately suppressing the immune response. Recognizing stress triggers and implementing effective stress management techniques can significantly impact individuals’ well-being. This review indicates that immune cells express genes differentially in response to stress, suggesting individual variabilities in the immune response against stress. This underscores the need for a personalized approach to stress management. This review also highlights the potential link between chronic stress and autoimmune disorders and warrants further investigation.
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![Figure 1 Pathways connecting stress to immune function. Stress activates the HPA axis and SNA, releasing catecholamines (noradrenaline) and glucocorticoids. These hormones alter immune cell behavior, increasing inflammatory cytokines and redistributing immune cells. This has effects on organs like the spleen and gastrointestinal tract, potentially influencing the microbiome. Abbreviations: IL: interleukin; Th17: T helper lymphocyte 17; CXCL12: homeostatic chemokine ligand; β2/β3-AR: β2/β3-adrenoceptors; Ach: acetylcholine; α7nAChR: α7 nicotinic acetylcholine receptor; HPA: hypothalamic–pituitary–adrenal axis; SNS: sympathetic nervous system; NA: noradrenaline; GC: glucocorticoids. Adapted from Ishikawa and Furuyashiki (2022) [36].](/paper-figures/2495783e07fa4892bd3efd66fa7b2b87/immunology-of-stress-a-review-article-figure-1.jpg)
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“Recent studies indicate that chronic psychological or physiological stress can exacerbate RA through neuro–immune–bone axis pathways [76]”
From Interorgan Communications in Skeletal Pathophysiology: From Molecular Pathways to Multidisciplinary Therapies (2026) · cites this paper as [76]
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Krefting, F., Hölsken, S., Sondermann, W., & Schedlowski, M. (2025) · Clinical Immunology · doi:10.1016/j.clim.2025.110611 · Cited by 2
Hagström, D., Sundström, A. E., Hakelind, C., Nordin, S., & Nordin, M. (2025) · Stress and Health · doi:10.1002/smi.70119 · Cited by 2
“…possible explanation for the fact that anxious tension and gastrointestinal problems were the strongest predictors of burnout is that both stress (Alotiby 2024) and gastrointestinal problems (Layunta et al. 2024) are associated with the immune response and a suppressed immune response is…”
Research Hotspots and Emerging Trends of Schizophrenia and Immune Response: A Bibliometric Analysis
Zhang, Y. (2025) · Brain and Behavior · doi:10.1002/brb3.71054 · Cited by 2
“Lastly, the interplay between stress and neuroinflammation represents an increasingly important area of research, as environmental stressors are known to activate inflammatory pathways, exacerbate oxidative stress, and worsen clinical outcomes in schizophrenia (Alotiby 2024; Ravi et al. 2021).”
Comparative Characterization of High-Grade Glioma Models in Rats: Its Importance for Neurobiology
Kudelkina, V. V., Bulava, A., Gorkin, A. G., Venerina, Y. A., & Alexandrov, Y. I. (2025) · Clinical and Translational Neuroscience · doi:10.3390/ctn9040058 · Cited by 2
Mazon, C., Betters, R. K., Salmeron-Ceballos, G., Tomaziefski, A., Coffman, C. N., Simonson, R., & Tunc‐Ozcan, E. (2026) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2026.01.003 · Cited by 2
“Stress further amplifies these sex-specific responses by increasing microglial reactivity (Schramm & Waisman, 2022) and elevating pro-inflammatory cytokine production (Alotiby, 2024), which in turn can alter synaptic remodeling, neurotransmitter dynamics, and circuit excitability.”
Targeting immunometabolism in cancer through pharmacological and lifestyle interventions
Tan, R. J. Y., Liu, Y., Chen, W., Liang, Y., & Ling, G. S. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003617 · Cited by 2
“Indeed, it is known that low glucose availability triggers the secretion of cortisol via the HPA axis as a stress response mechanism [114], and that elevated cortisol correlates with poor immune activation and function [115].”
Dera, A. A., Alqahtani, L. M., & Alghamdi, A. (2025) · King Khalid University journal of health sciences. · doi:10.4103/kkujhs.kkujhs_18_25 · Cited by 2
Su, W., Ai, Z., Liu, J., Yang, B., Du, T., & Zhang, R. (2026) · Building and Environment · doi:10.1016/j.buildenv.2026.114436 · Cited by 2
El‐Raghi, A. A., Fawzy, M. S., Elmorsy, E. M., Doghaither, H. A. A., Al-Ghafari, A. B., Hassan, M. S., Gad, A. M. A., Abourashed, N. M., & Abdelhady, D. (2026) · Italian Journal of Animal Science · doi:10.1080/1828051x.2026.2639681 · Cited by 2
Circadian misalignment in PCOS: role of sleep and light
Samaddar, S., Ghosh, S., Kumar, A., Yadav, P., Yadav, M., & Dahiya, R. (2026) · Biological Rhythm Research · doi:10.1080/09291016.2026.2651558 · Cited by 2
“Its effect on immune function and mood control should be considered seriously, and supplementation should be closely monitored to avoid any adverse effects (Alotiby 2024).”
Zheng, M., Sun, S., & Lv, B. (2026) · Journal of International Medical Research · doi:10.1177/03000605261447130 · Cited by 2
“13,14 The pathogenesis of IBS involves multiple interrelated mechanisms, with key contributing factors including visceral hypersensitivity, low-grade inflammation, impaired intestinal barrier function, gastro-intestinal motility disorders, psychological disturbances, brain–gut axis (BGA)…”
Domestic Violence Law and Maqāṣid al-Syarī’ah in Protecting Families from Psychological Violence
Nasyiah, I., Nasrulloh, M., Humairoh, Z., Fakhruddin, F., & Saidon, R. (2026) · Unnes Law Journal · doi:10.15294/ulj.v12i1.48249 · Cited by 2
Valiente-Gómez, A., Bücker, J., Fontana-McNally, M., Gatto, D. L., Guinart, D., Moreno‐Alcázar, A., Rodriguez, C. C., Gil, C. D. C., Padberg, F., Pardina-Torner, H., et al. (2026) · EClinicalMedicine · doi:10.1016/j.eclinm.2026.103987 · Cited by 2
Zhou, H., Wang, X., & Sha, S. (2026) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2026.1829622 · Cited by 2
“…promoting inflammatory factors, activating natural killer cells and macrophages, and recruiting white blood cells via corticosterone and adrenaline (Alotiby, 2004), whereas chronic stress impairs immune function, inhibits lymphocyte proliferation, disrupts cytokine balance, and, through prolonged…”
Nys, L. D. (2026) · Journal of Geriatric Oncology · doi:10.1016/j.jgo.2026.102854 · Cited by 2
Gan, D., Qin, L., & Xiao, G. (2026) · Research · doi:10.34133/research.1319 · Cited by 1
“Recent studies indicate that chronic psychological or physiological stress can exacerbate RA through neuro–immune– bone axis pathways [ 76 ].”
Andong, F. A., Okoye, K. C., Nnachi, I. A., Attamah, G. N., Odo, U. U., Mayowa, E. S., Agina, O. A., Ekere, S. O., Ngonadi, J. U., Nwanozie, P. O., et al. (2025) · Avian Biology Research · doi:10.1177/17581559251345277 · Cited by 1
Complex war trauma in an adolescent: diagnosis and rehabilitation (clinical case)
Kabantseva, A. V., Панченко, О. А., Tsapro, N. P., & Serdyuk, I. A. (2025) · CHILD`S HEALTH · doi:10.22141/2224-0551.20.6.2025.1897 · Cited by 1
Mishra, S., & Mohanty, B. (2025) · Nutrire · doi:10.1186/s41110-025-00369-9 · Cited by 1
“In our study, LPS enhanced the pro-oxidants (LPx) and decreased the antioxidants (SOD, CAT) levels in immune organs (spleen and thymus) as observed in others [72, 73].”
Chakma, J., Choravada, D. R., & Champati, A. (2025) · Cogent Food & Agriculture · doi:10.1080/23311932.2025.2573872 · Cited by 1
“…2009). these enzymes include superoxide dismutase (sOd), catalase (cAt), and Glutathione Peroxidase (GPx) (ighodaro & Akinloye, 2018; Jomova et al., 2024). the expression of antioxidant enzyme genes is regulated by transcription factors, primarily nrf2 (ngo & duennwald, 2022). under normal…”
Stocker, A., Giangreco, B., Revet, A., Alameda, L., Bui, É., Bürgin, D., Clemens, V., Cortese, S., Schechter, D. S., Schmid, M., et al. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106393 · Cited by 1
Luo, Z., Huang, Y., Tang, L., Gao, Q., Hou, G., Shao, J., & Shen, Y. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115921 · Cited by 1
Botia, M., Muñoz-Prieto, A., Ortín-Bustillo, A., Maslov, D. R., Rubić, I., Fuentes, P., Jiménez-Caparrós, F. J., Hernández-Gómez, J. L., Avellaneda, A., Cerón, J. M. C., et al. (2026) · Animal Welfare · doi:10.1017/awf.2025.10055 · Cited by 1
“This is consistent with evidence that stress induces the release of hormones and neuro-transmitters that modulate the function and movement of immune cells (Alotiby 2024).”
Coulter, J. E. (2026) · The Design Journal · doi:10.1080/14606925.2026.2625752 · Cited by 1
“To adapt to stress the body produces cortisol until the body’s resources have been depleted and it moves to exhaustion stage (McFarlane, 2024). ongoing and un-managed stress significantly impacts the immune system, affecting susceptibility to illness and overall health (Alotiby, 2024).”
Stress as a factor in female reproductive health disorders
Adamyan, L. V., Avetisyan, J. S., Osipova, A. A., Pivazyan, L. G., Mailova, K. S., & Saakyan, S. V. (2026) · Russian Journal of Human Reproduction · doi:10.17116/repro20263201111 · Cited by 1
Mityuryayeva-Kornijko, I. O., Klets, T., Burlaka, I. A., Коротич, Т. І., & Odayskyi, O. M. (2026) · Eastern Ukrainian Medical Journal · doi:10.21272/eumj.2026;14(1);126-137 · Cited by 1
Inorganic biomaterials as immunomodulators: dual strategies for activation and suppression
Si, X., Lu, Y., & Zha, Z. (2026) · Science China Materials · doi:10.1007/s40843-025-4001-x · Cited by 1
ЕКСПЕРИМЕНТАЛЬНЕ ДОСЛІДЖЕННЯ ВПЛИВУ ГОРМОНІВ СТРЕСУ НА НЕСПЕЦИФІЧНУ ПРОТИПУХЛИННУ ІМУННУ ВІДПОВІДЬ
Gogol, S., Федосова, Н. І., & Чехун, В. Ф. (2026) · Oncology · doi:10.15407/oncology.2026.01.031 · Cited by 1
“…відомо, глюкокортикоїди мають подвійний вплив на імунну відповідь: у коротко-строкові терміни вони посилюють активність імунних клітин (зокрема ПКК та Мф) та сприя-ють виробленню ними прозапальних цитокінів; тривалий вплив призводить до порушення імунної регуляції та розвитку імуносупресії [17–19].”
Risk Factors for Secondary Immunodeficiency in the Aged
Lang, A., Grammatikos, A. P., Ballow, M. C., Otani, I. M., & Barmettler, S. (2026) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2026.05.022 · Cited by 3
Xu, Y., He, P., Kang, X., Liu, P., & Xu, C. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1784930 · Cited by 1
“First, psychological stress, immune-stress responses, motivation, adherence, sleep, behavioral activation, and caregiver or social-support indicators should be recorded, because stress-related immune pathways may influence both recovery capacity and biomarker interpretation (38).”
Papachristodoulou, E., Kakoullis, L., Christophi, C. A., Derk, C. T., Chatzittofis, A., Alexopoulos, P., Καρανικόλας, Μ., Velissaris, D., & Parperis, K. M. (2026) · Rheumatology International · doi:10.1007/s00296-026-06183-4 · Cited by 1
“Chronic psychological stress activates neuroendocrine stress pathways, primarily the hypothalamic-pituitary-adrenal axis (HPA) and the sympathetic nervous system, resulting in alterations in cortisol and catecholamine signaling that influence immune regulation [ 5].”
Babayeva, Z., Babayeva, A., & Miller, A. H. (2026) · Shusha Scientific Journal · doi:10.66366/ssj.2026.66 · Cited by 1
Olia, J. B. H., Nikanfar, M., Avci, Ç. B., Khalilnezhad, A., Shahriyari, E., & Nourazarian, A. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149826 · Cited by 1
Russu, E.-A., Popa, L. G., Burcea, A., Bohîlțea, L. C., Bogdan-Andreescu, C. F., Banateanu, A. M., Poalelungi, C.-V., & Albu, C.-C. (2025) · Romanian Journal of Oral Rehabilitation · doi:10.62610/rjor.2025.2.17.51 · Cited by 1
Jaimes, M. S. V., Chaimano, S., Lin, S., Chang, Y., Yang, C.-T., Hsieh, S., Goh, J. O. S., Chu, Y.-W., & Tsai, M. (2025) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2025.107624 · Cited by 1
Metadata
- Authors
- Alotiby, A.
- Affiliations
- Umm al-Qura University (SA)
- Corresponding author
- Alotiby, Amna
- ORCID
- Alotiby, Amna
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2024-10-25
- Volume
- 13
- Issue
- 21
- Pages
- 6394
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC11546738
- OpenAlex
- W4403749058
- Cited by
- 253
- References
- 51
- Citations by year
- 2026: 145 · 2025: 108
- FWCI
- 9.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Stress, Anesthesia, and Immune Response
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- stress, immune system, hypothalamic-pituitary-adrenal axis, sympathetic nervous system, cortisol, chronic stress, acute stress, immune cell trafficking, neuroendocrine-immune interaction, microglia, stress hormones, stress management, autoimmune disease, immune gene expression
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