Periodontitis and Its Treatment on Circulating Inflammatory Cell Profiling: A Systematic Review and Meta-Analysis

Abstract

Background: Inflammation is a key driver of common non-communicable diseases. Among common triggers of inflammation, chronic gingival inflammation (periodontitis) triggers a consistent humoral host inflammatory response but little is known on its impact on the circulating peripheral cell profiles. Our aim was to critically appraise the whole existing evidence linking periodontitis and its treatment to circulating inflammatory cell profiles. Methods: In this systematic review and meta-analysis, we searched Cochrane CENTRAL, MEDLINE, Embase, Web of science, Scopus, and CINAHL databases for studies published in English up to 1 March 2021. Case-control, non-randomised and randomised controlled trials that reported the impact of periodontitis and its treatment on circulating inflammatory cell populations and functions were included. Qualitative and quantitative (meta-analysis) syntheses were performed. Weighted mean difference (WMD) with 95% CI of percentage of cell populations values between periodontitis patients and healthy controls were calculated in random effects models. Risk of Bias, including publication and heterogeneity were considered. Findings: Of 12687 studies identified, 157 were eligible for qualitative synthesis and 29 for meta-analysis. Participants with periodontitis exhibited a mean increase in circulating CD4+ (WMD of 0∙04, 95% CI 0∙01 to 0∙07, p=0·0144) and decrease in CD8+ lymphocytes (WMD of -0∙02, 95% CI -0∙04 to -0∙01, p=0∙0075). Peripheral blood neutrophils of patients with periodontitis consistently showed an elevated production of reactive oxygen species (ROS) when compared to those of healthy controls. Some evidence suggested that the treatment of periodontitis reversed the exaggerated ROS production but limited and inconclusive data was found on several circulating inflammatory cell profiling. Peripheral naive cytotoxic T (CD8+CCR7+CD45RA+), T helper (CD4+CCR7+CD45RA+), and effector T helper (CD4+CD45RA+) lymphocytes increased, whereas myeloid dendritic (CD1C+CCR6+), Th17 (CD4+IL-17+Foxp3+/-), CD8+ effector memory, and B (CD19+) lymphocytes decreased after periodontal treatment. Interpretation: Periodontitis and its treatment cause minor but consistent alterations in circulating inflammatory cell profiles. These changes could represent key mechanisms explaining the association of periodontitis with other co-morbidities such as cardiovascular diseases, diabetes, and rheumatoid arthritis. FundingNIHR-BRC at UCL/UCLH and Indonesia Endowment Fund for Education Registration Information: This study was registered with PROSPERO, CRD42020199995. Funding Information: NIHR-BRC at UCL/UCLH and Indonesia Endowment Fund for Education. Declaration of Interests: We declare no competing interests.