Journal of Prevention and Treatment for Stomatological Diseases ›› 2021, Vol. 29 ›› Issue (12): 828-835.doi: 10.12016/j.issn.2096-1456.2021.12.005

• Clinical Study • Previous Articles     Next Articles

Changes and clinical significance of four biomarkers in gingival crevicular fluid after nonsurgical periodontal therapy

ZHANG Qian1(),CHEN Bin2,YAN Fuhua2()   

  1. 1. Department of Pediatric Dentistry, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China
    2. Department of Periodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China
  • Received:2021-04-22 Revised:2021-05-27 Online:2021-12-20 Published:2021-08-17
  • Contact: Fuhua YAN E-mail:xzybyy@foxmail.com;yanfh@nju.edu.cn
  • Supported by:
    Cultivation Plan for the Establishment of Clinical Medicine Research Centers By The Provinces(2019060009);Key Project of Science and Technology Bureau of Jiangsu Province(BL2013002)

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Abstract:

Objective To study the changes in levels of interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), and alkaline phosphatase (ALP) in the gingival crevicular fluid (GCF) of patients with severe chronic periodontitis before and after nonsurgical periodontal therapy and to explore the relationship among the levels of these four biomarkers in GCF, their periodontal status and their clinical significance to evaluate the effect of nonsurgical periodontal therapy and periodontitis activity. Methods In total, 30 patients with severe chronic periodontitis were enrolled in a 1-year longitudinal pilot study (Chinese Clinical Trial Registry: ChiCTR-OCH-13004679). At baseline and 1, 3, 6, and 12 months after nonsurgical therapy, the periodontal clinical indicators plaque index (PLI), probing depth (PD), clinical attachment loss (CAL), sulcus bleeding index (SBI) were recorded. Filter paper strips were used to collect two deep-pocket (probing depth ≥ 6 mm) and two shallow-pocket (probing depth ≤ 4 mm) periodontal sites for each patient and weighed. The levels of interleukin IL-6, IL-10, TNF-α, and ALP in GCF were assessed using enzyme-linked immunosorbent assay. Meanwhile, 30 healthy sites of 15 subjects with healthy periodontium were used as the baseline controls for patients with severe chronic periodontitis. Results At the baseline, the TNF-α, ALP and IL-6 levels in GCF of the disease sites of patients with periodontitis were significantly higher than those in healthy periodontal sites of the control group (P < 0.001), and the levels of IL-10 were significantly lower than those in the control group (P < 0.001). In patients with severe chronic periodontitis, the levels of TNF-α, ALP and IL-6 in GCF at deep-pocket sites were significantly higher than those at shallow-pocket sites (P <0.001), and the IL-10 levels were significantly lower than those at shallow-pocket sites (P < 0.001). 1, 3, 6, and 12 months after nonsurgical treatment, the levels of TNF-α and ALP in GCF at the shallow- and deep-pocket sites in patients with chronic periodontitis significantly decreased, the level of IL-10 significantly increased (P < 0.005), and the level of IL-6 in GCF at the deep-pocket sites significantly decreased (P < 0.005). However, there was no significant difference in IL-6 level at shallow-pocket sites (P > 0.05). 1, 3, 6, and 12 months after nonsurgical treatment, the periodontal clinical indicators were improved compared with the baseline. In addition, there was a significant correlation between the levels of these four biomarkers and the periodontal clinical parameters (P < 0.05). During the two follow-up visits after nonsurgical periodontal therapy, the sites with more than 2-mm increase in attachment loss had significant differences in the levels of the four biomarkers in the GCF compared with the previous visit time (P < 0.005). Conclusion The detection of the levels of these four biomarkers in GCF has strong clinical significance for assessing the severity of periodontitis and the efficacy of nonsurgical periodontal therapy. Increased levels of TNF-α, ALP, and IL-6 and decreased IL-10 levels in GCF may indicate periodontitis progression at this site.

Key words: biomarkers, IL-10, TNF-α, IL-6, ALP, gingival crevicular fluid, nonsurgical periodontal therapy, severe chronic periodontitis, clinical trial

CLC Number: 

  • R78

Table 1

Levels of biomarkers in GCF at periodontitis sites in patients with severe chronic periodontitis at baseline and healthy sites in the control group Median (IQR)"

Group IL-6 (pg/site) IL-10 (pg/site) TNF-α (pg/site) ALP (pg/site)
Control 0.30(0.21,0.61) 1.34(0.62,1.74) 1.65(0.62,2.65) 129.7(22.31,192.8)
SPP 2.05(1.16,2.82)1) 0.62(0.29,0.89)1) 2.90(2.45,4.16)1) 272.1(210.3,519.8)1)
DPP 6.32(3.50,9.42)1)2) 0.31(0.10,0.61)1)2) 6.51(1.45,9.82)1)2) 905.2(457.9,1744)1)2)

Figure 1

Levels of IL-6, TNF-α, IL-10, and ALP in the GCF of deep-pocket and shallow-pocket sites at the baseline and 1, 3, 6 and 12 months after nonsurgical periodontal therapy a: IL-6; b: IL-10; c: TNF-α; d: ALP; *: compared with the baseline, P < 0.005. 1, 3, 6, and 12 months after nonsurgical therapy, the levels of TNF-α and ALP in GCF at the shallow- pocket (PD ≤ 4 mm) and deep-pocket (PD ≥ 6 mm) sites significantly decreased, the level of IL-10 significantly increased (P < 0.005), and the IL-6 level in GCF at the deep-pocket sites significantly decreased. IL-6: interleukin-6; IL-10: interleukin-10; TNF-α: tumor necrosis factor α; ALP: alkaline phosphatase; PD: probing depth"

Figure 2

Clinical indicators of deep pocket and shallow pocket sites at the baseline and 1, 3, 6 and 12 months after nonsurgical periodontal therapy a: PD; b: CAL; c: PLI; d: SBI; *: compared with the baseline, P < 0.005. 1, 3, 6, and 12 months after nonsurgical therapy, PD and CAL in the GCF at the shallow-pocket (PD ≤ 4 mm) and deep-pocket (PD ≥ 6 mm) sites significantly decreased, and PLI and SBI in the GCF at the deep pocket sites significantly decreased; PD: probing depth; CAL: clinical attachment loss; PLI: plaque index; SBI: sulcus bleeding index; GCF: gingival crevicular fluid"

Table 2

Correlation between periodontal parameters and the levels of biomarkers in GCF"

Parameters IL-6 IL-10 TNF-α ALP
PD(mm) P < 0.000 1 P < 0.000 1 P < 0.000 1 P < 0.000 1
r=0.758 r=-0.633 r=0.697 r=0.676
CAL (mm) P < 0.000 1 P<0.000 1 P < 0.000 1 P < 0.000 1
r=0.703 r=-0.594 r=0.729 r=0.687
PLI P=0.003 P=0.007 P=0.004 P=0.003
r=0.374 r=-0.256 r=0.398 r=0.372
SBI P=0.001 P=0.004 P=0.003 P=0.002
r=0.477 r=-0.389 r=0.380 r=0.459

Table 3

Levels of biomarkers in GCF at the sites of periodontitis progression 1, 3, 6, and 12 months after nonsurgical periodontal therapy $\bar{x}±s$"

Biomarkers and
clinical parameters		 1 month/baseline 3 months/1 month 6 months/3 months 12 months/6 months
sites/total, ratio 8/120, 6.67% 12/120, 10% 10/120, 8.33% 12/120, 10%
IL-6(pg) 6.72±1.071)/5.71±0.87 5.16±0.481)/4.18±0.45 6.31±0.891)/4.71±0.50 6.10±1.001)/4.46±0.74
TNF-α(pg) 6.99±0.931)/5.67±0.62 4.72±0.611)/3.85±0.70 5.70±0.841)/4.08±0.49 5.54±0.781)/4.33±0.86
IL-10(pg) 0.37±0.041)/0.50±0.03 0.42±0.061)/0.60±0.04 0.47±0.071)/0.77±0.10 0.80±0.171)/1.30±0.17
ALP(pg) 1 372.45±221.141)/1 071.29±208.25 1 091.54±243.481)/514.36±35.28 672.39±103.691)/441.23±70.15 642.34±130.291)/343.27±52.36
CAL(mm) 7.44±0.821)/5.31±0.75 7.12±0.611)/4.96±0.54 7.05±0.721)/4.75±0.75 7.33±0.721)/5.08±0.70
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