title: Salivary biomarkers in a biofilm overgrowth model.
abstract: BACKGROUND
  The purpose of this study is to determine whether baseline salivary inflammatory biomarkers could discriminate between different clinical levels of disease and/or detect clinical changes over a 3-week stent-induced biofilm overgrowth (SIBO) period.
  
  
  METHODS
  A total of 168 participants were enrolled in a 21-day experimental gingivitis investigation and grouped according to clinical measures of periodontal status of health and diseased individuals representing each of five biofilm gingival interface (BGI) periodontal groups: 1) health, all probing depth (PD) <3 mm and bleeding on probing (BOP) <10%; 2) gingivitis, all PD <3 mm and BOP ≥10%; 3) periodontitis (P)1, ≥1 site with PD >3 mm and BOP ≤10%; 4) P2, ≥1 site with PD >3 mm and BOP >10% but ≤50%; and 5) P3, ≥1 site with PD >3 mm and BOP >50%. Stents were used to prevent plaque removal during brushing over one maxillary and one mandibular posterior dental sextant for 21 days. Clinical periodontal parameters and unstimulated saliva were collected at screening, baseline, and each week during SIBO. Saliva samples were assessed for levels of 13 different biomarkers by multiplex immunoassay.
  
  
  RESULTS
  Higher salivary levels of interleukin (IL)-1β, matrix metalloproteinase (MMP)-3, MMP-8, MMP-9, and neutrophil gelatinase-associated lipocalin (NGAL) were found in diseased groups compared with the healthy group at baseline. Conversely, higher IL-1 receptor antagonist (ra) levels were found in healthy patients at baseline. In addition, during SIBO, MMP-1, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 levels increased across all participant groups. A stepwise linear regression model using all salivary biomarkers demonstrated that, at baseline, increased IL-1ra (P = 0.004) and IL-6 (P = 0.009) were significantly associated with change in PDs during SIBO.
  
  
  CONCLUSIONS
  In summary, this investigation supports salivary levels of IL-1ra and IL-6 as potential indicators for PD changes during induced gingival inflammation. In addition, participants from the BGI-P3 group (severe periodontitis) demonstrated elevated baseline levels of IL-1β, MMP-3, MMP-8, MMP-9, and NGAL compared with the other study groups, strengthening the relevance of participants' biologic phenotype on expression of salivary biomarkers.
authors: Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors: Thiago
authors: T
authors: Morelli
authors: Michael
authors: M
authors: Stella
authors: Silvana P
authors: SP
authors: Barros
authors: Julie T
authors: JT
authors: Marchesan
authors: Kevin L
authors: KL
authors: Moss
authors: Steven J
authors: SJ
authors: Kim
authors: Ning
authors: N
authors: Yu
authors: Marcelo B
authors: MB
authors: Aspiras
authors: Marilyn
authors: M
authors: Ward
authors: Steven
authors: S
authors: Offenbacher
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000328:Adult; D000368:Aged; D018441:Biofilms / Q000254:growth & development*; D015415:Biomarkers / Q000032:analysis*; D015331:Cohort Studies; D003773:Dental Plaque / Q000382:microbiology; D005260:Female; D005881:Gingiva / Q000378:metabolism; D005891:Gingivitis / Q000382:microbiology; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D000071068:Lipocalin-2; D054834:Lipocalins / Q000032:analysis; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020784:Matrix Metalloproteinase 8 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D010518:Periodontitis / Q000145:classification / Q000382:microbiology; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012463:Saliva / Q000737:chemistry*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C507763:IL1RN protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Cytokines; diagnosis; periodontitis; saliva