{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:58:49Z","timestamp":1793134729336,"version":"4.5.0"},"reference-count":142,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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-\u03b1, IL-1\u03b2, IL-6 and high-sensitivity C-reactive protein (hs-CRP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 (I\u00b2) 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From 216 observations (14,374 paired values), intensive NSPT led to significantly greater reductions in TNF-\u03b1 (SMD \u20130.59, 95% CI \u20131.02 to \u20130.16;\n                      <jats:italic>P<\/jats:italic>\n                      =0.008), IL-6 (SMD \u20130.20, 95% CI \u20130.39 to \u20130.00;\n                      <jats:italic>P<\/jats:italic>\n                      =0.046) and hs-CRP (SMD \u20131.17, 95% CI \u20132.18 to \u20130.16;\n                      <jats:italic>P<\/jats:italic>\n                      =0.024) compared to standard therapy. IL-1\u03b2 showed a near-significant reduction (SMD \u20134.14,\n                      <jats:italic>P<\/jats:italic>\n                      =0.052). Standard therapy was paradoxically associated with greater CRP reduction (SMD \u20130.30,\n                      <jats:italic>P<\/jats:italic>\n                      =0.001). Age, tooth count and year of publication moderated effects. Early benefits emerged within 3 months for TNF-\u03b1 and 6 months for IL-1\u03b2. Although no strong nonlinear time-response was confirmed (QM = 4.23,\n                      <jats:italic>P<\/jats:italic>\n                      =0.2372),a potential rebound in cytokine suppression was suggested. The overall anti-inflammatory effect remained significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:uri>https:\/\/www.crd.york.ac.uk\/PROSPERO<\/jats:uri>\n                      , identifier CDR42024503063.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1634622","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T05:24:45Z","timestamp":1756358685000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Temporal dynamics of early inflammatory markers after professional dental cleaning: a meta-analysis and spline-based meta-regression of TNF-\u03b1, IL-1\u03b2, IL-6, and (hs)CRP"],"prefix":"10.3389","volume":"16","author":[{"given":"Martina","family":"Cardisciani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Di Nicolantonio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Altamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Ortu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Del Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Pietropaoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.18-0006","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition","volume":"89","author":"Tonetti","year":"2018","journal-title":"J Periodontol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/0022034520908533","article-title":"Global, regional, and national levels and trends in burden of oral conditions from 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