INTERRELATIONSHIP OF PERIODONTAL AND ENDODONTIC INFECTIONS WITH SYSTEMIC INFLAMMATORY RESPONSES: A CLINICAL INVESTIGATION

Abstract

Periodontal and endodontic infections cause chronic inflammatory conditions of the oral cavity that can lead to systemic inflammatory activity via unique, but possibly overlapping, immune processes. This study evaluated the association between periodontal disease burden and systemic inflammatory markers and characterized inflammatory molecular signatures in chronic apical periodontitis. A secondary-data analytical design integrated independent clinical and transcriptomic analyses. Periodontal examination, C-reactive protein (CRP), and complete blood count data were used to assess systemic inflammatory profiles according to periodontal severity, probing pocket depth, and clinical attachment loss. Group comparisons, Spearman correlations, and robust linear regression were performed. Processed single-cell transcriptomic data from chronic apical periodontitis were independently analyzed to identify cell-specific inflammatory markers and mechanistic domains. CRP, white blood cell count, neutrophils, lymphocytes, monocytes, platelets, and platelet-to-lymphocyte ratio differed significantly across periodontal severity categories. Continuous periodontal measures showed weak but significant associations with CRP and selected leukocyte markers, while severe periodontitis was associated with higher log-transformed CRP. Chronic apical periodontitis showed high expression of inflammatory markers associated with myeloid/macrophage, epithelial, stromal and lymphoid cell populations, such as S100A8, S100A9, CXCL8, IL1B, CCL3, CCL4, and CCL5. Therefore, the systemic inflammatory associations of periodontal disease were modest, while those of chronic apical periodontitis had significant levels of local inflammatory transcriptional activity and did not indicate distinctive participant-level inflammatory links; however, inflammatory pathways converged.