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

Objective To investigate the use of peri-implant crevicular fluid (PICF) interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), 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-1 beta, IL-6, and TNF-alpha, 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-1 beta, IL-6, and TNF-alpha, 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-1 ss 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-1 ss and IL-6, can be used as adjunct tools to clinical parameters to differentiate H from MU and PI.