Study Year of
publication 		Study design Number of patients
(implants) 		Assessed PISF biomarker/enzyme Type of assay Main findings
Panagos et al. [7] 1996 CS 13 (17 H, 27 M, 26 P) IL-1β, TNF-α, pro- IL-1β ELISA H group had very low levels of IL-1β and pro- IL-1β when compared to other groups.
Hultin et al. [20] 2002 CS 37 (114 H, 45 P) IL-1β ELISA No difference between peri-implant health and disease condition according to IL-1β levels.
Wang et al. [21] 2015 CS 68 (34 H, 34 P) IL-1β, VEGF, MMP-8, TIMP-2, and OPG ELISA Increased levels of these biomarkers with site-specific microbial profile may be associated with peri-implant diseases.
Yaghobee et al. [22] 2014 CS 8 (16): 8 P, 8 H IL-1β and IL-6 ELISA Significant differences exist in the levels of IL-1β and IL-6 in the crevicular fluid of implants with peri-implantitis versus healthy implants.
Wohlfahrt et al. [23] 2014 INT (32 P) (before and after surgical treatment) IL-6, OPG, OC, leptin, OPN, PTH,TNF-α, adiponectin and insulin ELISA and Luminex A significant reduction in total protein, MMP -8, IL-6, OPG, leptin and adiponectin levels were demonstrated after surgical treatment.
de Mendonça et al. [24] 2009 INT 10P TNF-α ELISA Total amount of TNF-α was significantly reduced at 3 and 12 months after therapy (open flap debridement) compared to baseline.
Schierano et al. [25] 2008 INT 25 (25 H) TNF-α, TGF-β2 and IL-1β ELISA After de novo plaque accumulation; no significant changes observed in the total amount of TNF-α, IL-1β and TGF-β2 compared to baseline in PICF.
Duarte et al [26] 2009 INT 35 (10 H, 10 M, 20 P) IL-4, IL-10, IL-12, TNF-α, RANKL, OPG ELISA Levels of TNF-α was significantly higher in P and M, TNF-α levels of diseased implants decreased from baseline to 3 months after therapies, no differences among groups for IL-4, IL-10, IL-12 and the OPG/RANKL ratio was higher for healthy implants than for untreated peri-implantitis.
Lachmann et al. [27] 2007 INT 21 (42) IL-1β and PGE2 ELISA No difference between peri-implant health and disease condition.
Basegmez et al. [29] 2012 Longitudinal 28 (72) PGE2 and MMP-8 ELISA PGE2 and MMP-8 demonstrated positive correlations with gingival index and probing depth.
Ramseier et al. [30] 2016 CS (504 implant 493 adjacent teeth) IL-1β, MMP-3, MMP-8, MMP-1, and MMP-1 bound to tissue inhibitor of MMP (TIMP)-1 (MMP-1/TIMP-1) ELISA Increased levels of MMP-8 and IL-1β in PISF or GCF may be associated with inflammation around teeth and implants while lower levels of MMP-1/TIMP-1 may be an indicator of disease progression around implants.
Nomura et al. [31] 2000 CS 6 (10) MMP-8 ELISA Increased MMP-8 levels were found in peri-implantitis.
Ma et al. [32] 2000 CS 13 (49) Collagenase 2 and 3 Time-resolved immunofluorometric assay and quantitative immunoblot Collagenase-2 and collagenase-3 were higher in the group which had lost > 3 mm of bone than in the two other groups (bones loss < 3 mm).
Ma et al. [33] 2003 CS 12 (46) Gelatinase B Modified urokinase assay Gelatinase B is associated with peri-implant bone loss.
Casado et al. [35] 2013 CS 30 (10 H, 10 M,10 P) IL-1β and IL-10 ELISA IL-1β levels were lower in healthy group compared with Groups B and C. IL-10 levels were higher in Groups A compared with B.
Petković et al. [36] 2010 CS 90 (49 H, 30 M, 11 advanced M) IL-1β, TNF-α, IL-8 and MIP-1a ELISA Patients from the control group (healthy patients) have significantly lower concentrations of IL-1 β, TNF-α, IL-8 and MIP-1a in PICF compared with both groups with mucositis.
Ata-Ali et al. [38] 2013 CS 34 (23 H-54 M) IL-1β and IL-6 ELISA The mucositis group showed a significantly greater expression of IL-6 than the healthy group.
Lachmann et al. [39] 2007 CS 29 (36 H, 17 P) IL-1β, PAI-2 and PGE2 ELISA Increased PAI-2 levels in P group when compared to H group. No significant differences between healthy and diseased groups according to IL-1β levels.
Melo et al. [40] 2012 CS 31 (31 H, 16 P) IL-1β and IL-6 ELISA No significant differences between healthy implants and implants having peri-implantitis according to IL-1β and IL-6 concentration.
Renvert et al. [41] 2015 CS (41 P) IL-17, IL-1β, IL-1ra, IL-6, IL-8, IP-10, MIP-1a, PDGF, TNF-a and VEGF Luminex magnet bead technology Profuse bleeding and/or suppuration in untreated peri-implantitis can be associated with higher concentrations of IL-1β, IL-8, TNF-α and VEGF in PICF.
Yaghobee et al. [42] 2013 CS 32 (41 implant 41 contralateral tooth) IL-1β ELISA The positive correlation between the level of IL-1β and PI, GI, PD and BL in both groups was observed.
Fonseca et al. [43] 2014 CS 22 (60 M, 50 P) IL-1β, IL-2, IL-4,IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IFN-γ and TNF-α Multiplexed immunoassay The levels of IL-1β levels were significantly higher in P sites compared to M sites.
Güncü et al. [44]. 2012 CS 8 (20 H, 27 M) IL-1β, IL-10, RANKL, and OPG ELISA IL-1β, IL-10 and OPG levels in PISF were significantly higher in inflamed implants.
Aboyoussef et al. [45] 1998 CS (37 H, 37 P) IL-1β and PGE2 ELISA PGE2 in healthy sites were not significantly different from those at diseased sites. IL-1β was higher in implants with peri-implantitis.
Luo et al. [46] 2011 CS (20 H, 25 P) IL-1β, IL-6, IL-8, TNF-α ELISA Highest concentrations of IL-1β, IL-6, IL-8, TNF-α in the P group.
Ata-Ali et al. [47] 2015 CS 35 (54 H, 24 P) IL-8, IL-1β, IL-6, IL-10 and TNF-α Flow cytometry IL-1β, IL-6 , IL-10 and TNF-α were significantly higher at sites with peri-implantitis compared to healthy peri-implant tissue, IL-8 did not show significant difference.
Darabi et al [48] 2013 CS (18 H, 24 P) TNF-α, IL-17 ELISA TNF-α, IL-17 levels in the P group were higher with H group.
Güncü et al [50]. 2008 RCT (111 tooth site, 109 implant site) MPO Spectrophotometrically Total MPO levels were higher at inflamed implant sites compared to non-inflamed/healthy sites.
Liskmann et al. [51] 2006 CS 25 (64) MPO Spectrophotometrically Total amounts of MPO were significantly higher in PISF collected around implants with inflammatory lesions.
Tözüm et al. [52] 2007 CS 21 (67 tooth, 42 implant site) MPO and NO Spectrophotometrically PISF from inflamed sites had higher MPO and nitrite content than non-inflamed sites.
Plagnat et al. [53] 2002 CS 8 (11 P), 7 (11H) Elastase, alpha2-macroglobulin and alkaline phosphatase ELISA In comparison to the clinically healthy implants, total amounts of each of these substances were significantly higher in PICF collected around implants with peri-implantitis.
Yamalik et al. [54] 2011 CS (60 teeth, 68 implant) Cathepsin K Cathepsin-K activity assay kit More cathepsin-K activity was clearly observed with inflammatory periodontal and peri-implant destruction.
Arikan et al. [55]. 2011 CC 12 (18 P), 16 (21 H) ICTP, sRANKL and OPG ELISA Total amounts of ICTP were significantly higher, sRANKL concentrations, OPG total amounts, and OPG concentrations were significantly lower peri-implantitis group when compared to healthy group.
Rakic et al. [56]. 2013 CS 70 (23 P, 25 H) sRANKL, RANK and OPG ELISA sRANKL, RANK and OPG concentrations were significantly higher in peri-implantitis sites when compared to those in healthy implant sites.In these sites all three markers were significantly correlated with the clinical parameters.
Murata et al. [57] 2002 CC 16 (6 P, 8 M, 20 H) OC, deoxypyridinoline and IL-1β ELISA OC levels in PICF from mucositis sites were significantly higher than healthy implants whereas peri-implantitis sites were not significantly different from either mucositis or healthy implant sites. IL-1β levels in PICF from peri-implantitis sites were significantly higher than peri-implant mucositis and healthy implant sites.
Tümer et al. [58] 2008 CS 15 (30 P) ICTP and OC Radioimmunoassay A significant increase was noticed for OC PISF level in peri-implantitis sites compared with healthy ones.
Rakic et al. [59] 2014 CS (52 P, 54 M, 58 H) RANK, soluble RANKL, OPG, cathepsin-K, and sclerostin. ELISA Concentrations of RANK, sRANKL, OPG, and sclerostin were significantly increased in patients with peri-implantitis compared with patients with healthy peri-implant tissues.
Severino et al. [60] 2011 CS 14 (20 P), 11 (20 H) IL-6, IL-10 and IL-17 and the chemokine IL-8 ELISA The expression of IL-17 was significantly higher in the P group when compared to H.
Monov et al. [61] 2006 CS 16 (19) RANKL Immunuassay Absolute amounts of sRANKL showed no correlation with the adsorbed volume and the clinical parameters PD, MBI, and MPI.
Fiorellini et al. [62] 2000 CS 20 (59) AST Spectrophotometrically Utilizing the site or implant as the unit of measure, the authors found a statistically significant association of increased AST activity with positive bleeding on probing, increased probing depth, and increased GI.
Zhang et al. [63] 2005 CS 56 (23 H, 35 M, 8 P) IL-6 ELISA IL-6 was significantly higher in P compared with M and H.

CS = cross-sectional; INT = interventional; CC = case-control; RCT = randomized clinical trial; PICF = peri-implant crevicular fluid; PISF = peri-implant sulcus fluid; IL = interleukin; P = peri-implantitis; M = mucositis; H = healthy; TNF = tumour necrosis factor; VEGF = vascular endothelial growth factor; MMP = matrix metallo proteinase; TIMP = tissue inhibitor of matrix metallo proteinase; OPG = osteoprotegerin; PTH = parathyroid hormone; OC = osteocalcin; OPN = osteopontin; TGF = transforming growth factor; RANKL = receptor activator of nuclear factor kappa B ligand; PGE = prostoglandine; MIP-1alpha = macrophage inflammatory protein-1alpha; PAI-2 = plasminogen activator inhibitor type 2; PDGF = platelet derived growth factor; IFN = interferone; MPO = myeloperoxidase; NO = nitricoxide; ICTP = C-telopeptide pyridinoline crosslinks of Type I collagen; AST = Aspartat amino transferase; PD = probing depth; GI = gingival index; PI = plaque index; MBI = modified bleeding index; MPI = modified plaque index.