The associations between gingival crevice fluid matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 and periodontitis in human immunodeficiency virus-positive patients

J Periodontal Res. 2006 Dec;41(6):491-7. doi: 10.1111/j.1600-0765.2006.00887.x.


Background and objective: The study aimed to determine whether matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in gingival crevice fluid could serve as prognostic factors for the progression of periodontitis in human immunodeficiency virus (HIV) -positive patients. Activated inflammatory cells produce inflammatory mediators, which stimulate the production of MMPs and their inhibitors. It is likely that the compromised immune system contributes to the pathogenesis of periodontitis in HIV-positive patients.

Methods: Clinical measurements including gingival index, plaque index, bleeding index, probing depth, attachment loss, and gingival crevice fluid samples were taken from two healthy sites (including sites with gingival recession, gingival index = 0; probing depth < or = 3 mm; attachment loss < or = 2 mm), three gingivitis sites (gingival index > 0; probing depth < or = 3 mm; attachment loss = 0) and three periodontitis sites (gingival index > 0; probing depth > or = 5 mm; attachment loss > or = 3 mm) of each of the 35 patients at baseline visits and 6-month visits by means of paper strips. Gingival crevice fluid levels of MMP-9 and TIMP-1 were determined by sandwich enzyme-linked immunosorbent assays.

Results: The mean amounts of MMP-9 and TIMP-1 in the gingivitis and periodontitis sites sites were significantly higher than in the healthy sites (P < 0.0001). The progressing site was defined as a site that had 2 mm or more attachment loss during the 6-month study period. Gingival crevice fluid levels of MMP-9 were significantly correlated with probing depth, attachment loss, TIMP-1, age, smoking pack years, and viral load values at baseline and 6-month visits (0.0001 < P < 0.001). TIMP-1 levels were only correlated with CD4, viral load, attachment loss, and MMP-9 (0.001 < P < 0.01). Repeated measures analysis of 11 active sites vs. 269 inactive sites indicated that MMP-9 and TIMP-1 levels were significantly higher in active sites than in inactive sites (P < 0.0001). These data indicate that sites with high ginigval crevice fluid levels of MMP-9 and TIMP-1 in HIV-positive patients are at significantly greater risk for progression of periodontitis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Biomarkers / analysis
  • CD4 Antigens / analysis
  • Disease Progression
  • Epidemiologic Methods
  • Gingival Crevicular Fluid / chemistry
  • Gingival Crevicular Fluid / enzymology*
  • HIV Infections / complications
  • HIV Infections / enzymology*
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / analysis*
  • Peptide Fragments / analysis
  • Periodontal Attachment Loss / complications
  • Periodontal Attachment Loss / enzymology
  • Periodontitis / complications
  • Periodontitis / enzymology*
  • Protease Inhibitors / analysis
  • Smoking / physiopathology
  • Tissue Inhibitor of Metalloproteinase-1 / analysis*
  • Viral Load


  • Biomarkers
  • CD4 Antigens
  • Peptide Fragments
  • Protease Inhibitors
  • Tissue Inhibitor of Metalloproteinase-1
  • CD4 (76-94)
  • Matrix Metalloproteinase 9