Proinflammatory and anti-inflammatory cytokines in modulating bone remodeling during orthodontic tooth movement

<h2>Abstract</h2><h3>Objectives</h3> This systematic review and meta-analysis sought to assess the influence of proinflammatory (interleukin [IL]-1β, IL-6, tumor necrosis factor α) and anti-inflammatory (IL-10, IL-4, IL-1RA) cytokines on bone remodeling during orthodontic tooth movement. The aim was to clarify their dynamics over time and space and evaluate their potential as clinical biomarkers. <h3>Search Strategy</h3> The review adhered to the Preferred Reporting Items for Systematic reviews and Meta-analyses 2020 guidelines. A structured population, intervention, comparator, outcome framework directed the search. Medical Subject Heading terms alongside free-text key words were used in combination with Boolean operators across various databases (PubMed, Embase, Scopus, Cochrane Library, Web of Science) from 2000 through 2024. The reference lists of the included studies were examined manually to ensure thoroughness. <h3>Citation Sources</h3> Searching electronic databases and conducting manual reference checks resulted in an initial collection of 85 studies of which 14 met the criteria for inclusion. <h3>Study Selection Criteria</h3> The studies eligible for inclusion measured cytokine levels (IL-1β, IL-10, IL-1RA, IL-4) in gingival crevicular fluid, saliva, or serum throughout orthodontic treatment. No age, sex, or appliance type restrictions were imposed on the participants. Both observational and interventional human studies were considered. <h3>Data Elements Included</h3> Data extraction included details such as authorship, methodology, biological fluid examined, cytokines investigated, detection technique (enzymed-linked immunosorbant assay, multiplex assay, polymerase chain reaction), sample size, and key outcomes. Quality assessment was conducted using the Newcastle-Ottawa Scale. <h3>Overall Conclusions</h3> Proinflammatory cytokines showed early peaks after the application of orthodontic force, triggering bone resorption at compression sites. In contrast, anti-inflammatory cytokines appeared later, facilitating repair and bone deposition at tension sites. IL-1β levels were positively correlated with the rate of tooth movement, while lower levels of IL-1RA were associated with quicker distal displacement. Although the pooled results from the meta-analysis did not show statistically significant differences, consistent trends supported the regulatory role of cytokines in orthodontic tooth movement. Future investigations should focus on larger, multicenter studies using standardized protocols to confirm the reliability of cytokines as biomarkers for precise orthodontic treatments.