Gingival crevicular fluid during experimental gingivitis: A review of immune and tissue regulation

BackgroundThis systematic review summarized the features of human experimental gingivitis (EG) in terms of immune responses and tissue remodeling in the gingival crevicular fluid (GCF).MethodsSystematic searches were conducted to screen the literature published from January 1960 to June 2024 from MEDLINE (PubMed), EMBASE, and Web of Science. The selected studies were prospective trials evaluating the immune responses and tissue remodeling mediators in GCF before and after EG via oral hygiene refrain. Evidence quality and risk of bias were assessed.ResultsThirty studies with 594 volunteers met the inclusion criteria, analyzing 74 clinical parameters and biomarkers in GCF samples. Consistent with EG induction, the EG sites showed an increase in plaque index (PI), gingival index (GI), and myeloperoxidase (MPO) (an indicator of neutrophil migration). In addition, the expression levels of interleukin (IL)‐1α and IL‐1β were increased, also consistent with the previous literature investigating active lesions of periodontal inflammation during gingivitis. However, the expression of macrophage inflammatory protein (MIP)‐1 β, monocyte chemoattractant protein (MCP)‐1, CCL2, and fractalkine/CX3CL1 decreased among EG in multiple studies demonstrating an EG effect on recruitment and cellular communication of mononuclear cells. In contrast, the levels of fibroblast growth factors (FGFs), vascular endothelial growth factor (VEGF), and anti‐inflammatory cytokines showed insignificant changes during EG induction. Aging, stress level, and the diabetes status of the volunteer populations affected the outcomes.ConclusionsThe features of acute inflammatory lesions of EG with limited tissue destruction showcase that it is a valuable tool to investigate the initial immune responses on gingival tissue against bacterial challenges.Plain Language SummaryThis review examined how human experimental gingivitis (EG) affects immune responses and tissue changes in the fluid around the gums. Researchers analyzed studies published from 1960 to 2024, focusing on those that looked at immune responses and tissue changes in gum fluid before and after participants stopped brushing their teeth to induce EG. The review included 30 studies with 594 participants, exploring various health markers in gum fluid. When EG was induced, areas of the gums showed increased plaque and markers of inflammation, indicating an inflammatory response. Specifically, two inflammatory proteins (interleukin [IL]‐1α and IL‐1β) were found in greater expression, which aligns with what previous research has shown in gum disease. However, levels of certain proteins that help attract monocytes and macrophages decreased, suggesting changes in how these cells communicate during EG. Additionally, the levels of growth factors and anti‐inflammatory substances did not change significantly. Factors such as age, stress, and diabetes also influenced the outcomes. These findings help us understand early immune responses in gum disease, which is crucial for developing prevention strategies and improving oral health overall.