Expression of inflammatory biomarkers and growth factors in gingival crevicular fluid at different healing intervals following non‐surgical periodontal treatment: A systematic review

Abstract

Background: Non-surgical periodontal treatment (NSPT) is widely employed for the treatment of periodontal disease and yields significant clinical improvements. Gingival crevicular fluid (GCF) can be used to profile health and disease, and recent technological advances, such as multiplex bead immunoassays, are promising in identifying a wider array of GCF factors with the ultimate aim to predict the treatment response. Objective: The aim of this systematic review was to compare the expression of GCF markers using multiplex bead immunoassays before treatment and during early, average, or late healing period, following non-surgical periodontal treatment (NSPT). Methods: An electronic literature search was conducted by two independent examiners (VK and NC) in MEDLINE, EMBASE, OpenGrey, LILACS, and Cochrane Library up to January 2020. The PICO question formulated was as follows: "In patients with periodontal disease, does the expression of gingival crevicular fluid (GCF) markers detected using multiplex bead immunoassay differ at baseline compared with early (≤30 days), average (6-8 weeks), or late (≥3 months) healing after intervention?" Results: A total of 366 publications were obtained and reviewed for eligibility for inclusion. Of these, 12 publications fulfilled the inclusion criteria and were included in the present review. Data for a total of 31 different GCF markers were extracted and summarized for early, average, or late healing after NSPT. Early healing following NSPT (≤ 30 days) indicated an increase in IL-1β, TNFα, and IL-10. At the average healing period (6-8 weeks), IL-1β, IL-1α, IL-6, TNF-α, IFN-γ, GM-CSF, MCP-1, and MIP-1α were all reduced, compared to their respective baseline values. Three months after NSPT, IL-1β, IL-4, IL-6, IL-10, TNF-α, and IFN-γ were detected at reduced levels, compared to pre-treatment levels. Overall, the changes following treatment indicated a reduction of inflammation present at baseline. Conclusion: Following non-surgical periodontal treatment, an upregulation of inflammation markers is noted early post-operatively and a subsequent reduction of their levels three months following treatment. The investigation of levels of GCF markers associated with inflammation and regeneration, especially using multiplex bead

Molecular profiling of intrabony defects' gingival crevicular fluid

“…The samples were read using a Luminex MAGPIX analyser (Luminex; R&D systems), and the concentrations for each marker were reported in pg/ml. The 27 GCF markers investigated were as follows 6,7 : angiopoietin-1 (Ang-1), bone morphogenic protein-2 (BMP-2), epidermal growth factor (EGF), basic fibroblast growth factor (FGFb), interferon-gamma (IFNγ), interleukin-1α (IL-1α), interleukin 1β (IL-1β), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-8 (MMP-8), osteopontin (OPN), platelet-derived growth factor-AA (PDGF-AA), derived growth factor-BB (PDGF-BB), tissue inhibitor metalloproteinase-1 (TIMP-1), tumor necrosis factor-alpha (TNFα), receptor activator of nuclear factor kappa-Β (RANKL), vascular endothelial growth factor (VEGF), bone morphogenic protein-7…”

“…Our group has previously identified a broad array of both inflammatory and regenerative markers present in the GCF following surgical treatment of intrabony sites 6 and following non-surgical treatment of conventional periodontitis sites. 7 In the present study, this wide array of markers was used to profile the GCF of intrabony defect sites and periodontally healthy sites, using multiplex immunoassays.…”

The secretion of cytokines by peripheral blood mononuclear cells of patients with periodontitis and healthy controls when exposed to H2S

“…In a systematic review and meta-analysis, it was reported that the levels of IL-1β, IFN- γ, MCP-1, and IL-6 in gingival crevicular fluid of periodontitis patients were higher than in healthy individuals, while no differences were observed for IL-12 and IL-17 [ 21 ]. Further, it was reported that the levels of IL-1β and IL-17 significantly decreased after periodontal treatment, while another systemic review reported reduced levels of, among others, IL-1β, IL-6, TNF-α, IFN- γ, and MCP-1, six to eight weeks after periodontal treatment [ 24 ]. Thus, the inflammatory mediators measured in our study have previously been linked to periodontitis.…”

Expression of Wnt signaling agonists and antagonists in periodontitis and healthy subjects, before and after non‐surgical periodontal treatment: A systematic review

“… Human studies Prospective clinical studies reporting on the expression of Wnt signaling agonists: Wnts, Norrin, R‐spondins (Rspo), and antagonists: Dickkopf proteins (Dkks), secreted frizzled‐related proteins (sFRPs), Wnt‐inhibitory factor 1 (WIF‐1), Wise/SOST, Cerberus, insulin‐like growth factor‐binding protein 4 (IGFBP‐4), Shisa, Wnt‐activated inhibitory factor 1 (Waif1/5 T4), adenomatosis polyposis coli down‐regulated 1 (APCDD1), and Tiki1 in the GCF, serum and/or gingival tissue Expression levels reported before and early (≤30 days) or late (3 months) after NSPT Only studies with at least 5 subjects per group were included in this review For this analysis, the follow‐up time points were classified as early, when the sampling occurred less than 30 days following the intervention and late, when the sampling occurred more than 3 months following the intervention 31,32 …”