What type of study is this?

This is a Meta-Analysis study (also classified as: Observational).

September 5, 2025Frontiers in Immunology0 citationsOpen Access

Temporal dynamics of early inflammatory markers after professional dental cleaning: a meta-analysis and spline-based meta-regression of TNF-α, IL-1β, IL-6, and (hs)CRP

MCMartina Cardisciani SNSara Di Nicolantonio SASerena Altamura

Key Points

Intensive nonsurgical-periodontal-therapy significantly reduces TNF-α and IL-6, indicating anti-inflammatory benefits.
With 216 observations, TNF-α saw a mean reduction of –0.59, while IL-6 dropped by –0.20 after intensive therapy.
Meta-regression revealed early benefits in inflammatory markers like TNF-α within 3 months and IL-1β within 6 months.
Although rebound in inflammatory markers is suggested, intensive therapy appears to reduce systemic inflammation, highlighting its importance.

Abstract

Introduction 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. Discussion 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. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO , identifier CDR42024503063.

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