Diederik Hentenaar

41 Biomarkers in crevicular peri-implant fluid Biomarker levels in diseased implants before and after non-surgical therapy Biomarker levels of untreated and treated peri-implantitis implants are presented in table 3b. The majority of biomarkers did not change at 3 months after therapy; levels of IL-1β and MMP-8 remained high. Moreover, a significant increase in median levels of chemokine MIP-1α/CCL3 (10.8 [7.2;17.9] pg/ml per 30 seconds versus 14.9 [9.4;30.0] pg/ ml per 30 seconds, p < .001) and anti-inflammatory growth factor G-CSF (0.0 [0.0;24.0] pg/ml per 30 seconds versus 32.3 [26.8;41.6] pg/ml per 30 seconds, p < .001 ) was seen at 3 months after treatment. DISCUSSION In this study, 10 host-derived biomarkers were assessed in PICF of healthy implants and compared with biomarkers in PICF of implants with peri-implantitis using a customized Luminex™ multiplex panel. Additionally, the effect of non-surgical peri- implantitis therapy on the 10 host-derived biomarkers was evaluated. Outcomes showed that implants with peri-implantitis had significantly higher levels of IL-1β and MMP-8 compared to healthy implants whereas no difference in levels of IL-6, TNF-α, MIP1-a/CCL3, MCP-1, OPG and G-CSF were found between both groups. Levels of sRANKL and INF-y appeared to be under using the customized Luminex™ panel in this study. The effect of therapy on these biomarkers, as well as on peri-implant clinical and radiographical outcomes, appeared low. Healthy versus diseased biomarker levels in PICF Classical pro-inflammatory cytokines (IL-1β, TNF-α and IL-6), alone or in combination, belong to the most frequent investigated immunological markers in relation to peri- implant disease. Recent systematic reviews and meta-analyses have indicated moderate evidence in the literature to support that pro-inflammatory cytokines could differentiate between peri-implant health and peri-implant disease, especially regarding levels of IL-1β and TNF-α (Faot et al. 2015, Duarte et al. 2016, Ghassib et al. 2019). This study seems to be in accordance with this finding for levels of IL-1β, underlining the potential adjunctive role for this marker in the diagnosis of peri-implantitis. In contrast to IL-1β, we were not able to find a difference between health and disease for levels of TNF-α and IL-6. Although it is hypothesized in the literature that TNF-α or IL-6, next to IL-1β, are potential diagnostic markers, a recent meta-analysis by Ghassib et al. (2019) has shown that the literature on these markers is still scarce and with a high level of heterogeneity. Especially for levels for IL-6 limited evidence has been found to discriminate between peri-implantitis and healthy implants. In accordance with our study, two previous studies did not find a difference between implants with peri-implantitis and healthy 2