SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Mucosal Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1634622
This article is part of the Research TopicImmunology in Oral DiseasesView all articles
Temporal dynamics of early inflammatory markers after professional dental cleaning: a metaanalysis and spline-based meta-regression of TNF-α, IL-1β, IL-6, and (hs)CRP
Provisionally accepted
Martina CARDISCIANI
Sara Di Nicolantonio
Serena Altamura
Eleonora Ortu
Rita Del Pinto*
Davide Pietropaoli*- University of L'Aquila, L'Aquila, Italy
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Background: Chronic periodontitis is linked to systemic inflammation and cardiovascular risk, yet the temporal trajectory and magnitude of systemic cytokine reduction following nonsurgical-periodontal-therapy (NSPT) remain underexplored. We conducted a meta-analysis and spline-based meta-regression to assess whether intensive NSPT, compared to standard therapy, produces sustained reductions in circulating TNF-α, IL-1β, IL-6 and high-sensitivity C-reactive protein (hs-CRP). Methods: We systematically searched major databases for interventional studies published until January 2024 comparing intensive vs. standard NSPT on inflammatory markers. Using a custom R pipeline, standardized mean differences (SMDs), 95% confidence intervals (Cis) heterogeneity (I²) and stratified analyses by phenotype (e.g., smoking, diabetes) and time were performed. A spline-based mixed-effects meta-regression explored temporal dynamics of inflammatory reduction in the intensive group. Results: From 216 observations (14,374 paired values), intensive NSPT led to significantly greater reductions in TNF-α (SMD –0.59, 95% CI –1.02 to –0.16; P=0.008), IL-6 (SMD –0.20, 95% CI –0.39 to –0.00; P=0.046) and hs-CRP (SMD –1.17, 95% CI –2.18 to –0.16; P=0.024) compared to standard therapy. IL-1β showed a near-significant reduction (SMD –4.14, P=0.052). Standard therapy was paradoxically associated with greater CRP reduction (SMD –0.30, P=0.001). Age, tooth count and year of publication moderated effects. Early benefits emerged within 3 months for TNF-α and 6 months for IL-1β. Although no strong nonlinear time-response was confirmed (QM = 4.23, P=0.2372),a potential rebound in cytokine suppression was suggested. The overall anti-inflammatory effect remained significant. Conclusions: Intensive NSPT reduces systemic inflammation particularly in younger, non-smoking individuals. The potential rebound in inflammatory markers underscores the need for longitudinal studies but, supports the systemic immunoregulatory effect of periodontal therapy
Keywords: Periodontitis, Inflammation, tumor necrosis factor-α, Interleukin-6, interleukin-1β, C-Reactive Protein, Cytokines, Meta-analysis
Received: 24 May 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 CARDISCIANI, Di Nicolantonio, Altamura, Ortu, Del Pinto and Pietropaoli. 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:
Rita Del Pinto, University of L'Aquila, L'Aquila, Italy
Davide Pietropaoli, University of L'Aquila, L'Aquila, Italy
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