The present study aimed to determine interleulin (IL)-6 and C-Reactive-Protein (CRP) levels in apical lesions of endodontic origin (ALEO) and to identify its potential sources in apical tissues.
Method:
Asymptomatic apical periodontitis patients and healthy volunteers consulting at the School of Dentistry, University of Chile were enrolled. ALEO and healthy periodontal ligaments were obtained and processed for either immunohistochemistry, DNA extraction for real-time RT-PCR, tissue homogenization and multiplex assay to determine IL-6 and CRP tissue localization, cytoplasmic RNA expression and protein levels, respectively. Primary periodontal ligament fibroblast tissue cultures were also performed and CRP synthesis was evaluated in response to IL-6, IL-6 soluble receptor (sIL-6R) alone and in combination. Statistic analysis was performed using unpaired t-test or Mann-Whitney test, according to data distribution, and Pearson’s correlation.
Results:
IL-6 and CRP demonstrated a similar pattern of tissue localization in apical granulomas and inflammatory radicular cysts, involving the inflammatory cell infiltrates, vascular endothelial cells and mesenchymal cells. Both, IL-6 and CRP were synthesized in ALEO, whereas their RNA expression and protein levels were significantly higher when compared with healthy periodontal ligament (p<0.05). In fact, healthy controls demonstrated almost no detection of IL-6 and CRP, but healthy periodontal ligament fibroblasts were able to produce CRP when stimulated with IL-6 in combination with sIL-6R.
Conclusion:
CRP synthesis can be induced in healthy periodontal fibroblasts in response to IL-6. Under inflammatory conditions, both IL-6 and CRP are locally produced and overexpressed in ALEO. Local synthesis of IL-6 and CRP in apical tissues might partially explain the development and progression of ALEO, as well as potentially AAP-associated systemic low grade inflammation.