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Conventional therapy, involving professional mechanical plaque removal (PMPR) and oral hygiene instruction, faces limitations involving disease recurrence and patient factors. This systematic review explores immunomodulatory therapies as alternative or adjunctive treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>MEDLINE (Ovid), EMBASE (Ovid), Cochrane Database of Systematic Reviews and MEDLINE (Web of Science) databases were searched on 9 June 2024. Two authors independently screened the articles using pre-specified inclusion and exclusion criteria, and findings were grouped by immunomodulatory agent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The search retrieved 2363 records, and 42 were included. Thirteen types of immunomodulatory agents were evaluated across cell lines, animal models of PD, and observational studies and clinical trials in humans. Several agents showed evidence of effects on inflammation and alveolar bone loss; however, the quality and consistency of evidence varied. Limited data suggest that longer treatment duration, alternative delivery methods, or combination approaches may enhance therapeutic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Immunomodulatory agents show promise for the management of PD, including in patients with co-morbidities. However, clinical evidence in the context of conventional therapy and safety data remain limited. Further rigorous trials are needed to confirm efficacy, optimise treatment, and evaluate long-term safety before these therapies can be incorporated into routine clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12903-026-08120-0","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T06:15:12Z","timestamp":1781504112000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunomodulation as a novel treatment strategy for periodontal disease: a systematic review"],"prefix":"10.1186","volume":"26","author":[{"given":"Fariad","family":"Akbar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Czesnikiewicz-Guzik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"8120_CR1","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1111\/jre.13050","volume":"57","author":"AH Abidi","year":"2022","unstructured":"Abidi AH, Abhyankar V, Alghamdi SS, Tipton DA, Dabbous M. 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