Immunomodulatory Roles of Interleukins in Root Canal Healing: A Molecular Perspective on Endodontic Sealer Biocompatibility

Background: Effective root canal treatment is not only associated with the eradication of infection but also with responses of tissue to endodontic adhesives. The periapical immune microenvironment, especially interleukin (IL) signaling, is essential for periapical healing. The purpose of this study was to determine the immunomodulatory functions of ILs during root canal healing and assess the molecular biocompatibility with endodontic sealers. Methods: In this cross-sectional study, 90 human periodontal ligament fibroblast (hPDLF) samples were exposed to 3 sealers (Bioceramic, zinc oxide eugenol (ZOE), and epoxy resin). ELISA was used to measure cytokine levels (IL-1b, IL-6, IL-8, IL-10); osteogenic markers, including Alkaline Phosphatase (ALP), Runt-related TF-2 (RUNX2), and Osteocalcin (OCN), were quantified by real-time qPCR, and cell viability by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. ANOVA and Chi-square tests were used to analyze data, where p < 0.05 was considered significant. Results: Bio-ceramic sealers exhibited maximum IL-10 (99.7 ± 8.7) and osteogenic markers expression and significantly reduced IL-6 (116.2 ± 13.7) and IL-8 (106.8 ± 12.2) expressions (p < 0.001). Epoxy resin was moderately biocompatible. ZOE had higher pro-inflammatory cytokines (132.1, 245.8, 202.6 for IL-1b, IL-6, and IL-8, respectively) and lower cell viability (69.4 ± 6.1, p < 0.001). Conclusion: Bio-ceramic sealers indicated better immunomodulatory and regenerative capabilities, which favors their use in clinical practice for root canal treatment. These findings highlight the requirement for molecular compatibility during the selection of the sealer.