Your new experience awaits. Try the new design now and help us make it even better

SYSTEMATIC REVIEW article

Front. Bioeng. Biotechnol.

Sec. Tissue Engineering and Regenerative Medicine

This article is part of the Research TopicTissue Engineering Strategies and Biomaterials in Oral and Maxillofacial Hard Tissue Injury RepairView all 11 articles

Clinical effect of immunomodulatory therapy in periodontitis: A Systematic Review and Meta-analysis

Provisionally accepted
Yubing  ZhangYubing Zhang1Xu  QinXu Qin1Jiexuan  YangJiexuan Yang1Hannah  M RogersHannah M Rogers1Babak  BabanBabak Baban2Siwei  TianSiwei Tian2*
  • 1Huazhong University of Science and Technology, Wuhan, China
  • 2Augusta University, Augusta, United States

The final, formatted version of the article will be published soon.

Objectives: To evaluate the clinical effect of immunomodulatory therapy in periodontitis, and to identify the possible key inflammatory factors to intervene to modulate the immune status and improve periodontal conditions. Materials and methods: An electronic search was conducted for human-based studies published until October 2025 on MEDLINE (PubMed), ISI Web of Science, EMBASE, and the Cochrane Database. Randomized controlled trials (RCTs) comparing the effectiveness of immunotherapy and placebo were included. We also compared cytokine levels between the immunotherapy group and the non-immunotherapy group to identify the specific inflammatory mediators influenced by immunotherapy but not by SRP (Scaling and Root Planning). Meta-analyses with fixed and random effects models were performed. Risk of bias assessment was also performed for randomized controlled trials. Results: Of the 34 articles selected, 22 were included in the meta-analysis(n=991). It was found that immunomodulatory therapy improved clinical attachment level (CAL), bleeding from probing (BOP), and depth of probing (PD) in patients with periodontitis. A three-group meta-analysis showed that immunotherapy affected periodontal disease progression by modulating local immune factors IL-1β, IL-17, IL-6, IL-8 and TNF-α, thus providing a potential statistically significant benefit. Conclusion: Immunotherapy influenced periodontal disease progression through the modulation of local immune factors. The data support the use of immunotherapy as an adjunct to conventional mechanical therapy. Further investigations are warranted to elucidate sources of heterogeneity of the results and examine the potentiality of using inflammatory cytokines as novel targets for the treatment of periodontal disease.

Keywords: Periodontitis, clinical trials, Immunomodulation, Immunotherapy, Systematic review

Received: 27 Aug 2025; Accepted: 27 Oct 2025.

Copyright: © 2025 Zhang, Qin, Yang, Rogers, Baban and Tian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Siwei Tian, tiansw@139.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.