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.

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; =0.008), IL-6 (SMD -0.20, 95% CI -0.39 to -0.00; =0.046) and hs-CRP (SMD -1.17, 95% CI -2.18 to -0.16; =0.024) compared to standard therapy. IL-1β showed a near-significant reduction (SMD -4.14, =0.052). Standard therapy was paradoxically associated with greater CRP reduction (SMD -0.30, =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, =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.