Endodontic treatment modifies circulatory inflammatory mediator levels: A systematic review with meta-analysis

Background: There is limited and conflicting data on the reduction of circulatory inflammatory mediators in patients with apical periodontitis (AP) following endodontic treatment. Objective: To answer the following research question: in adult healthy patients with AP [Population (P)], is there a difference before [Comparator (C)] and after various endodontic treatments (nonsurgical, surgical or retreatment) [Intervention (I)] on systemic levels of inflammatory biomarkers [Outcome (O)] in the follow-up period [Time (T)]? Methods: An electronic literature search was conducted in the databases Scopus, PubMed, Clarivate Analytics' Web of Science, Cochrane Database of Systematic Reviews and Grey literature from inception to July 2024 with no language restrictions. Observational studies examining changes in serum levels of inflammatory mediators were included. Two independent reviewers selected studies, extracted data and critically appraised the included studies. Qualitative and quantitative (meta-analysis) data synthesis methods were employed. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Results: Sixteen studies met the inclusion criteria, of which six were included in the meta-analysis. These studies were published between 1992 and 2024, involving a total of 596 patients (54% females) aged between 16 and 75 years. The meta-analysis of pooled data showed a significant decrease in high-sensitive C-reactive protein (hs-CRP) levels in the serum of patients with AP 6 months after treatment [2.26 +/- 1.76 versus 1.28 +/- 1.06 mg/L, (Z = 2.03, p = .04)] and a decrease in interleukin-1 beta (IL-1 beta) levels 12 months after treatment [13.01 +/- 5.95 versus 10.86 +/- 3.52 pg/mL, (Z = 3.72, p < .01)]. One study was assessed as poor quality, while all others were considered high quality. Discussion: Despite the differences in methodologies across the included studies, it has been established that effective endodontic treatment leads to a reduction in systemic inflammatory biomarkers in the body. Conclusion: Following effective endodontic treatment in patients with AP, the systemic levels of hs-CRP and IL-1 beta exhibit a significant reduction at 6 and 12 months, respectively. Further clinical studies should investigate whether effective endodontic treatment and reduced levels of investigated biomarkers may change the clinical presentation of systemic diseases. Registration: PROSPERO database (CRD42024559271).