Cardisciani Martina, Di Nicolantonio Sara, Altamura Serena, Ortu Eleonora, Del Pinto Rita, Pietropaoli Davide
Department of Life, Health & Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Center of Oral Diseases, Prevention and Translational Research - Dental Clinic, L'Aquila, Italy.
Front Immunol. 2025 Aug 28;16:1634622. doi: 10.3389/fimmu.2025.1634622. eCollection 2025.
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).
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.
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.
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.
https://www.crd.york.ac.uk/PROSPERO, identifier CDR42024503063.
慢性牙周炎与全身炎症和心血管风险相关，但非手术牙周治疗（NSPT）后全身细胞因子降低的时间轨迹和幅度仍未得到充分研究。我们进行了一项荟萃分析和基于样条的荟萃回归，以评估与标准治疗相比，强化NSPT是否能持续降低循环中的肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和高敏C反应蛋白（hs-CRP）。
我们系统检索了主要数据库，以查找截至2024年1月发表的关于比较强化与标准NSPT对炎症标志物影响的干预性研究。使用自定义的R管道，进行标准化均值差异（SMD）、95%置信区间（CIs）、异质性（I²）分析以及按表型（如吸烟、糖尿病）和时间进行分层分析。基于样条的混合效应荟萃回归探讨了强化组炎症降低随时间的动态变化。
从216项观察结果（14374对数值）来看，与标准治疗相比，强化NSPT能使TNF-α（SMD -0.59，95% CI -1.02至-0.16；P = 0.008）、IL-6（SMD -0.20，95% CI -0.39至-0.00；P = 0.046）和hs-CRP（SMD -1.17，95% CI -2.18至-0.16；P = 0.024）显著降低更多。IL-1β显示出接近显著的降低（SMD -4.14，P = 0.052）。矛盾的是，标准治疗与更大程度的CRP降低相关（SMD -0.30，P = 0.001）。年龄、牙齿数量和发表年份会影响治疗效果。TNF-α在3个月内、IL-1β在6个月内出现早期益处。虽然未确认有强烈的非线性时间反应（QM = 4.23，P = 0.2372），但提示细胞因子抑制可能存在反弹。总体抗炎效果仍然显著。
强化NSPT可减轻全身炎症，尤其在年轻、不吸烟的个体中。炎症标志物的潜在反弹凸显了进行纵向研究的必要性，但也支持了牙周治疗的全身免疫调节作用。
