{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:31:14Z","timestamp":1791048674821,"version":"4.1.0"},"reference-count":194,"publisher":"Portland Press Ltd.","issue":"22","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,27]]},"abstract":"<jats:p>Periodontitis is a chronic inflammatory condition that gradually destroys the tissues supporting the teeth, including the gingiva, periodontal ligament, and alveolar bone. Emerging evidence suggests that psychological stress plays a significant role in the initiation and progression of periodontal disease, primarily through its impact on immune regulation. Stressors activate the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis, leading to the release of corticotropin-releasing hormone (CRH) from the hypothalamus and, in turn, adrenocorticotropic hormone (ACTH) from the pituitary gland. Activation of the HPA axis and the sympathetic-adrenal-medullary (SAM) system during stress triggers the systemic release of cortisol, epinephrine, norepinephrine, and cytokines. The HPA, SAM, and cytokines interact in both direct and indirect ways. Not only does stress induce interleukin-10 (IL-10), but IL-10 also helps regulate the stress response and cortisol levels. IL-10 can stimulate the release of CRH and ACTH, while concurrently inhibiting cortisol secretion from the adrenal glands. IL-10 has drawn increasing attention within the oral cavity owing to its dual role in modulating immune responses and maintaining periodontal tissue homeostasis. This review outlines the current understanding of stress-related neuroendocrine pathways and their relevance to periodontal health. It explores the involvement of HPA axis effectors\u2014cortisol and IL-10\u2014in modulating the inflammatory milieu associated with periodontitis. This includes recent insights into IL-10-expressing regulatory B cells and the potential role of IL-10 in mitigating alveolar bone loss. By integrating recent advances in neuroendocrinology, immunology, and oral biology, this review clarifies how systemic stress responses contribute to local inflammatory changes in the periodontium. Understanding the mechanisms linking psychological stress, cortisol dynamics, and IL-10-mediated regulation may offer new opportunities for early diagnosis and intervention in stress-exacerbated periodontitis.<\/jats:p>","DOI":"10.1042\/cs20256843","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T16:06:13Z","timestamp":1764086773000},"page":"1469-1487","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Chronic stress and the IL-10-mediated immunoregulatory loop in the pathogenesis of periodontitis"],"prefix":"10.1042","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9552-4098","authenticated-orcid":false,"given":"Maksym","family":"Skrypnyk","sequence":"first","affiliation":[{"name":"1Centre for Health Informatics, Australian Institute of Health Innovation, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia"},{"name":"2Charles Perkins Centre, The University of Sydney, Sydney, NSW, 2050, Australia"},{"name":"3Sydney Dental School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2010, Australia"},{"name":"4Juntendo Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1714-5727","authenticated-orcid":false,"given":"Axel","family":"Spahr","sequence":"additional","affiliation":[{"name":"5Discipline of Periodontics, School of Dentistry, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2638-4121","authenticated-orcid":false,"given":"Shlomo","family":"Berkovsky","sequence":"additional","affiliation":[{"name":"1Centre for Health Informatics, Australian Institute of Health Innovation, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8601-1939","authenticated-orcid":false,"given":"Tetiana","family":"Yatsenko","sequence":"additional","affiliation":[{"name":"4Juntendo Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan"},{"name":"6Department of Enzymes Chemistry and Biochemistry, Palladin Institute of Biochemistry of NAS of Ukraine, Kyiv, 01054, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8831-3607","authenticated-orcid":false,"given":"Chun","family":"Xu","sequence":"additional","affiliation":[{"name":"2Charles Perkins Centre, The University of Sydney, Sydney, NSW, 2050, Australia"},{"name":"3Sydney Dental School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0559-6718","authenticated-orcid":false,"given":"Olga","family":"Zuieva","sequence":"additional","affiliation":[{"name":"4Juntendo Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Osada","sequence":"additional","affiliation":[{"name":"7Department of Gastroenterology, Juntendo University Urayasu Hospital, Urayasu-shi, Chiba, 279-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"8Division of Clinical Precision Research Platform, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, 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