The systemic effects of inflammation and the dynamics of cytokine profile in chronic apical periodontitis

Introduction . Chronic apical periodontitis (CAP), affecting 11,2 % of the world′s population and ranking sixth in prevalence, is a serious public health problem. Despite the studied pathology, there are still gaps in understanding both the systemic effects of inflammation and the peculiarities of the local inflammatory response. The aim of the study : to study the effect on inflammatory markers of the chronic periapical process with the description of the peculiarities of the inflammatory profile. Materials and methods . The study was conducted from August to December 2024 on the basis of Yaroslavl SMU and the Medical Centre for Diagnostics and Prevention «Sodrugestvo» (Yaroslavl). The study included 94 patients of both sexes divided into three groups: the group with symptomatic CAP — 35 people; the group with asymptomatic CAP — 33 people; the control group — 26 people. The study was single-centre, prospective. Three groups of patients were examined before and after treatment. The treatment of CAP consisted of extraction of the affected tooth, which allowed the assessment of changes in the inflammatory profile both locally and systemically. The examinations were performed at two time points: before treatment (baseline) and 5 weeks after tooth extraction (after regeneration was complete). To assess the inflammatory profile, the content of 5 pro-inflammatory and 4 anti-inflammatory cytokines was examined. Blood sampling was performed twice: immediately before tooth extraction and 5 weeks after surgery. The level of cytokines in plasma was analysed using a special panel of NPO «EcoMed» (Russia) on a «Clima MC-15» device («DIACON-DS JSC», Russia). The results of measurements were presented in pg/ml. Statistical analysis was performed using Statistica v.14 programme. Normality of data was assessed by the Shapiro–Wilk test. Continuous data were presented as mean M±m. Differences between groups were analysed using analysis of variances. Group profiles were constructed by cluster analysis procedures. The probability of error was at p <0,05. Results . The study showed a significant effect of CAP on inflammatory markers in peripheral blood. Before treatment, there was a significant increase in the levels of the pro-inflammatory cytokines IL -1β, IL -6, TNF-α and G-CSF in both symptomatic and asymptomatic patients compared to the control group. Multivariate analysis allowed us to identify characteristic features of the cytokine profiles for each group. A clear predominance of proinflammatory mediators was found in patients with symptomatic CAP, confirmed by high correlations between IL -1β and IL -6 (r=0,76), IL -1β and G-CSF (r=0,93). The asymptomatic group showed a less pronounced but still significant inflammatory response, characterized by moderate correlations of IL -1β with IL -6 (r=0,59) and TNF-α with OPG (r=0,62). The control group showed a balanced cytokine profile with low correlations between proinflammatory mediators (IL -1β and IL -6 r=0,38; TNF-α and RANKL r=0,26) and a dominance of anti-inflammatory factors. Changes in the ratio of OPG to RANKL confirmed the involvement of these proteins in the alteration of bone metabolism in CAP. After extraction of the offending tooth, statistically significant changes in OPG/RANKL parameters were observed, indicating the onset of bone regeneration processes. Conclusion. The influence of CAP on the systemic inflammatory profile has been established. An increase in the levels of pro-inflammatory cytokines IL -1β, IL -6, TNF-α and G-CSF in both symptomatic and asymptomatic forms was noted before tooth extraction compared to the control group. Multivariate analysis revealed unique cytokine profiles of each group: dominance of pro-inflammatory cytokines in symptomatic course, moderate inflammatory response in asymptomatic and balanced profile in control group. Changes in the OPG/RANKL ratio confirmed the modification of bone metabolism in CAP and its correction after treatment.