The Effect of Subgingival Antimicrobial Therapy on the Levels of Stromelysin and Tissue Inhibitor of Metalloproteinases in Gingival Crevicular Fluid

Pourtaghi, Nahid (1995) The Effect of Subgingival Antimicrobial Therapy on the Levels of Stromelysin and Tissue Inhibitor of Metalloproteinases in Gingival Crevicular Fluid. MSc(R) thesis, University of Glasgow.

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Abstract

Recent investigations imply that a key mechanism in the pathogenesis of periodontal disease may be the ability of oral micro-organisms to induce production and /or activation of matrix metalloproteinases in the host tissues. Stromelysin (SL) is a member of the matrix metalloproteinase family which may play a role in chronic inflammatory periodontitis. Extracellular control of these enzymes is performed by tissue inhibitor of metalloproteinases (TIMP) and during normal tissue turnover, inflammation and healing, levels of MMPs and TIMP will change. The effect of treatment on the levels of MMPs and inhibitors has been to decrease collagenase activity, to decrease the amount of collagenase and stromelysin (SL) produced, and to increase the level of TIMP. It has been suggested that the pharmacologic inhibition of MMP activity could play an important role in achieving a desirable outcome in periodontal therapy. In addition to antimicrobial effects, tetracyclines have been shown to be able to inhibit metalloproteinases (MMPs). However, recent results indicate that the inhibition of MMPs by systemic tetracycline depends on the drug concentration and type as well as the origin of the MMP. Therefore, theoretically a greater inhibitory effect on MMPs would be expected if higher concentrations of drug could be delivered to the site of action. Recently, there has been increasing interest in the use of locally delivered antibiotics in order to obtain a high concentration of the drug at the target site and to minimise potential systemic adverse effects. We therefore sought to investigate the efficacy of locally delivered antibiotics on the level of gingival crevicular fluid (GCF) stromelysin (SL) and tissue inhibitor of metalloproteinases (TIMP) on sites with a history of a poor response to mechanical treatment. 52 patients with 4 periodontal pockets >5 mm and bleeding on probing were randomised into four groups of 13 patients. One group received scaling and root planing alone and the other three groups received scaling and root planing plus a locally delivered antimicrobial system. These included 25% tetracycline fibre, 2% minocycline gel, and 25% metronidazole gel. The GCF samples taken at baseline and 6 weeks after treatments were analysed using an enzyme linked immunosorbent assay (ELISA). All treatments resulted in significant improvement in clinical parameters. The pocket depth reduction was significantly greater in the scaling plus tetracycline fibre group than the scaling alone group (p=0.003) . GCF SL levels significantly decreased after adjunctive tetracycline fibre (paired t-test, p=0.020) and minocycline gel (paired t-test, p=0.023) treatments whereas it remained almost unchanged in the other two groups. While the GCF TIMP level did not change significantly in the scaling and root planing alone XX group, it significantly increased for all three adjunctive antimicrobial treatments (for tetracycline fibre p<0.001, minocycline gel p=0.005, metronidazole gel p<0.001). The analysis of covariance (ANCOVA) on the baseline SL was used to reduce the error resulting from the variation in the baseline. The level of SL at baseline had a significant effect on the SL change following treatment (p<0.001), and this effect was positive i.e. the higher the baseline SL, the higher the reduction of SL. Treatment also had a significant effect on the reduction of SL (p=0.001). Follow-up analysis showed significant differences between; i) tetracycline fibre plus scaling and scaling alone groups (p=0.004); and ii) minocycline gel plus scaling and scaling alone groups Cp=0.002). There was a significant difference in TIMP levels between treatment groups (p=0.007). Furthermore, the analysis of TIMP levels revealed that a significant difference existed between the minocycline gel plus scaling and the scaling alone group (p=0.018), and also between the metronidazole gel plus scaling and the scaling alone group (p=0.001). Our observation that the mean level of SL decreased after antibiotic treatment could be explained by the fact that local delivery of antibiotics plus scaling and root planing may change the microbial flora. This may cause a larger decrease of SL than scaling and root planing alone. However, the greatest decrease was observed in the sites treated by tetracycline or minocycline delivery systems. Previous studies have also shown that tetracyclines, in addition to decreasing the level of periodontal bacteria, resulting in decrease of MMP activity in the gingiva, could decrease the synthesis of pro-MMPs and also protect the endogenous MMP inhibitors (TIMP-1) and other proteinase inhibitors (alpha1-antitrypsin) from degradation and inactivation by direct and indirect mechanisms. However, it cannot be established from this study whether the effect of the tetracyclines on the level of SL is direct, or indirect through the reduction in microbial challenge which could reduce the microbial proteases and inflammatory mediators such as cytokines, both of which could reduce the levels of human MMP. After treatment the level of free TIMP increased. This might be due to a reduction in MMPs which would bind to free TIMP.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Additional Information: Adviser: D F Kinane
Keywords: Dentistry
Date of Award: 1995
Depositing User: Enlighten Team
Unique ID: glathesis:1995-74866
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 27 Sep 2019 15:46
Last Modified: 27 Sep 2019 15:46
URI: http://theses.gla.ac.uk/id/eprint/74866

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