Effects of sub-antimicrobial dose doxycycline therapy on crevicular fluid MMP-8, and gingival tissue MMP-9, TIMP-1 and IL-6 levels in chronic periodontitis.
OBJECTIVE
To investigate whether sub-antimicrobial dose doxycycline (SDD) therapy for 120 d in chronic adult periodontitis patients had significant effects on gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) levels, and on gingival tissue MMP-9, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and interleukin-6 (IL-6) levels.


BACKGROUND
Tetracycline can significantly inhibit MMP activity in GCF and in gingival tissue, even in much lower dosage then a traditional antimicrobial dosage used in conventional therapy. Sub-antimicrobial dose doxycycline (SDD) therapy has been shown to reduce periodontal disease activity to control MMP and pro-inflammatory cytokines.


METHODS
A total of 32 patients with incipient to moderate (probing pocket depth approximately 4-7 mm) chronic adult periodontitis were included in the study. Subjects were randomly assigned to two groups. After scaling and root planning (SRP), the SRP + SDD group received SDD, 20 mg bid, whereas the SRP + placebo group received placebo, 20 mg bid. In the follow-up, efficacy measures included the change in probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) and gingival crevicular fluid MMP-8 levels, gingival tissue MMP-9, TIMP-1 and IL-6 levels from baseline to 120 d.


RESULTS
After 120 d, PD and CAL improved significantly in the SRP + SDD group. Initial MMP-8 levels for the SRP + SDD group and the SRP + placebo group were 407.13 +/- 114.45 ng/ml and 378.71 +/- 189.39 ng/ml, respectively, with no statistical difference between the two groups. MMP-8 levels for the SRP + SDD group and the SRP + placebo group were: 235.35 +/- 134.58 ng/ml and 364.04 +/- 219.27 ng/ml at 30 d; 157.50 +/- 95.95 ng/ml and 236.60 +/- 186.16 ng/ml at 60 d; 102.70 +/- 67.64 ng/ml and 208.56 +/- 124.54 ng/ml at 90 d; and 63.77 +/- 53.33 ng/ml and 229.13 +/- 168.09 ng/ml at 120 d, respectively. The amount of decrease in MMP-8 levels for the SRP + SDD group was statistically significant compared to that for the SRP + placebo group, especially apparent at 120 d (p < 0.05). TIMP-1 levels in both groups increased from the baseline to 120 d with statistical significance (p-value < 0.05), but there was no significant difference between the two groups. Changes in MMP-9 and IL-6 levels were not statistically significant.


CONCLUSIONS
Adjunctive SDD therapy can improve the clinical parameters and this clinical improvement is reflected by controlled level of MMP-8 in chronic adult periodontitis after the therapy.
Choi
Dong-Hoon
DH
Department of Periodontology, College of Dentistry, Yonsei University, Seoul, Korea.
Moon
Ik-Sang
IS
Choi
Bong-Kyu
BK
Paik
Jeong-Won
JW
Kim
Yoon-Sik
YS
Choi
Seong-Ho
SH
Kim
Chong-Kwan
CK
D000328:Adult; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002908:Chronic Disease; D012534:Dental Scaling; D004318:Doxycycline / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005883:Gingival Crevicular Fluid / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis*; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects*; D008875:Middle Aged; D010518:Periodontitis / Q000188:drug therapy* / Q000201:enzymology; D010919:Placebos; D011480:Protease Inhibitors / Q000032:analysis*; D016745:Root Planing; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D015850:Interleukin-6; D010919:Placebos; D011480:Protease Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline