Use of IL‐1 β, IL‐6, TNF‐α, and MMP‐8 biomarkers to distinguish peri‐implant diseases: A systematic review and meta‐analysis

Abstract

Objective To investigate the use of peri‐implant crevicular fluid (PICF) interleukin‐1β (IL‐1β), IL‐6, tumor necrosis factor‐α (TNF‐α), and matrix metalloproteinase‐8 (MMP‐8) biomarkers in distinguishing between healthy implants (H), peri‐implant mucositis (MU), and peri‐implantitis (PI). Material and Methods Electronic using three databases (Pubmed, EMBASE, and Cochrane) and manual searches were conducted for articles published up to March 2018 by two independent calibrated reviewers. Meta‐analyses using a random‐effects model were conducted for each of the cytokines; IL‐1β, IL‐6, and TNF‐α, to analyze standardized mean difference (SMD) between H and MU, MU and PI, H and PI with their associated 95% confidence intervals (CI). Qualitative assessment of MMP‐8 was provided consequent to the lack of studies that provide valid data for a meta‐analysis. Results Nineteen articles were included in this review. IL‐1β, IL‐6, and TNF‐α, levels were significantly higher in MU than H groups (SMD: 1.94; 95% CI: 0.87, 3.35; P < .001, SMD: 1.17; 95% CI: 0.16, 3.19; P = .031 and SMD: 3.91; 95% CI: 1.13, 6.70; P = .006, respectively). Similar results were obtained with PI compared to H sites (SMD: 2.21, 95% CI: 1.32, 3.11; P < .001, SMD: 1.72; 95% CI: 0.56, 2.87; P = .004 and SMD: 3.78; 95% CI: 1.67, 5.89; P < .001, respectively). IL‐6 was statistically higher in PI than MU sites (SMD = 1.46; 95% CI: 0.36, 2.55; P = .009); while IL‐1ß increase was not significant. Despite absence of meta‐analysis, MMP‐8 show to be a promising biomarker in detection of PI in literature. Conclusion Within the limitations of this study, pro‐inflammatory cytokines in PICF, such as IL‐1ß and IL‐6, can be used as adjunct tools to clinical parameters to differentiate H from MU and PI.

Biological response to peri‐implantitis treatment

“…Studies have detected MMP‐8 in saliva and GCF of periodontitis patients and in PICF of PIP patients suggestive that MMP‐8 levels may be useful for diagnostic monitoring of the connective tissue destruction phase of peri‐implant disease. MMP‐8, including targeting its active form, has been reported to represent a valuable target for chairside point‐of‐care testing of oral fluids related to detection of periodontitis, and more recently in PIP; albeit active MMP‐8’s ability to affect treatment decision‐making remains to be fully elucidated and implemented within the global dental profession. Similar to our findings, Wang et al did not observe significant differences in the concentration of MMP‐8 between healthy and PIP individuals, although the literature would support that differences in selection of antibody systems to detect these types of biomolecules can create variation in the levels and outcome measures between health and disease .…”

“…Biomarkers linked to PIP include an array of pro‐inflammatory cytokines (tumor necrosis factor‐α, interferon‐γ, interleukin (IL)‐1β, IL‐6, anti‐inflammatory cytokines (IL‐4 and IL‐10), chemokines (IL‐8, monocyte chemoattractant protein (MCP)‐1 and macrophage inflammatory protein (MIP‐1α), and tissue destructive enzymes (matrix metalloproteinases (MMP‐8) . Of these, pro‐inflammatory cytokines demonstrate the strongest association with PIP . However, additional studies are needed to establish their validity, help predict susceptibility, identify early biological indicators of failing implants and better quantify response to therapy …”

“…20,[27][28][29][30][31][32][33][34] Of these, pro-inflammatory cytokines demonstrate the strongest association with PIP. 20,27,28,35,36 However, additional studies are needed to establish their validity, help predict susceptibility, identify early biological indicators of failing implants and better quantify response to therapy. 37 Based on these findings, we hypothesized that concentrations of IL-1β, MMP-8, and MIP-1α would demonstrate a biological response to surgical and antimicrobial therapy relative to clinical improvement.…”

Peri-Implantitis Diagnosis and Prognosis Using Biomarkers in Peri-Implant Crevicular Fluid: A Narrative Review

“…Contrary to what was found with IL-1β, IL-6 increases significantly between PIM and PI. IL-6 links innate and acquired immune responses, in which it induces differentiation of activated B cells into antibody-producing cells as well as naïve CD4+ T cells [36]. Studies of experimental PIM demonstrated that TNFα and TGF-β2 levels did not change during an experimental PIM period.…”

“…MMP upregulation has been associated with irreversible peri-implant connective tissue destruction [42]. One suggested reason for MMP upregulation is polymorphism in the promoter region of MMP-8 which explains varied responses between different individuals with the same disease category [36]. During the initiation and course of inflammatory responses in PI, proinflammatory mediators including MMP-8 are up-regulated in affected tissues and present in PICF [51].…”