Whole Salivary Interleukin‐6 and Matrix Metalloproteinase‐8 Levels in Patients With Chronic Periodontitis With and Without Prediabetes

Background: The cytokine profile in unstimulated whole saliva (UWS) of patients with prediabetes and chronic periodontitis (CP) remains uninvestigated. The aim of this study is to assess interleukin (IL)‐6 and matrix metalloproteinase (MMP)‐8 levels in UWS of patients with CP with and without prediabetes. Methods: Eighty‐eight males (aged 39 to 51 years) were divided into three groups: group 1: 28 patients with CP and prediabetes; group 2: 30 patients with CP and without prediabetes; and group 3: 30 controls. Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels, periodontal parameters (plaque index, bleeding on probing, probing depth, attachment loss, and marginal bone loss), and number of missing teeth were recorded. UWS samples were collected, and UWS flow rate (UWSFR) was measured. IL‐6 and MMP‐8 were measured in UWS using enzyme‐linked immunosorbent assay. P values <0.05 were considered statistically significant. Results: Mean FBG and HbA1c levels were significantly higher in group 1 (119.3 ± 3.1 mg/dL and 6.1% ± 0.2%) than group 2 (80.1 ± 3.5 mg/dL and 4.8% ± 0.5%; P <0.001) and group 3 (75.3 ± 2.2 mg/dL and 4.3% ± 0.2%; P <0.05). UWSFR was significantly higher in groups 2 (0.53 ± 0.1 mL/minute; P <0.05) and 3 (0.51 ± 0.1 mL/minute; P <0.01) than group 1 (0.33 ± 0.05 mL/minute). Periodontal parameters were worse in group 1 (P <0.05) and group 2 (P <0.05) than group 3. There was no difference in periodontal parameters, numbers of missing teeth, or salivary IL‐6 and MMP‐8 levels between patients in groups 1 and 2. Conclusion: Salivary IL‐6 and MMP‐8 levels are elevated in patients with CP with and without prediabetes.     

The Influences of Periodontal Status and Periodontal Pathogen Quantity on Salivary 8‐Hydroxydeoxyguanosine and Interleukin‐17 Levels

Background: Periodontitis is a biofilm‐initiated disease that is characterized by elevated inflammatory status. 8‐Hydroxydeoxyguanosine (8‐OHdG) and interleukin (IL)‐17 are highly associated with inflammation and bone resorption and therefore are regarded as potential biomarkers for periodontitis. In this study, the associations between salivary 8‐OHdG and IL‐17 levels and clinical and microbial parameters before and after non‐surgical treatment are investigated. Methods: Forty‐five patients with chronic periodontitis (CP) and 47 periodontally healthy volunteers were recruited for the study. Clinical parameters, including the probing depth (PD), clinical attachment level (CAL), sulcular bleeding index, and simplified oral hygiene index (OHI‐S), were examined for each participant. Microbial parameters including the quantities of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola in the subgingival plaque and saliva were determined by real‐time polymerase chain reaction at baseline and 1 and 3 months after the non‐surgical treatment. Salivary 8‐OHdG and IL‐17 levels were detected by enzyme‐linked immunosorbent assays. Results: Compared with healthy volunteers, CP group patients had significantly higher salivary 8‐OHdG and IL‐17 levels at baseline. Baseline salivary 8‐OHdG and IL‐17 levels were positively correlated with all clinical parameters as well as the quantities of T. forsythia and T. denticola. After non‐surgical treatment, baseline levels of salivary 8‐OHdG and IL‐17 were reduced significantly at both the 1‐ and 3‐month follow‐ups. The hierarchical linear model revealed that variations in the PD, CAL, and OHI‐S had significant positive effects on variation in the salivary 8‐OHdG level. However, variations in the PD; quantity of T. forsythia in the subgingival plaque; and quantities of P. gingivalis, T. forsythia, and T. denticola in saliva were associated significantly with variation in the salivary IL‐17 levels. Conclusions: There was a strong association between salivary 8‐OHdG and IL‐17 levels and periodontitis. Variation in the salivary 8‐OHdG level was correlated with variations in the clinical parameters, whereas variation in the IL‐17 level was correlated with variation in the microbial parameters.     

Assessment of Interleukin‐6 Receptor Inhibition Therapy on Periodontal Condition in Patients With Rheumatoid Arthritis and Chronic Periodontitis

Background: Overproduction of interleukin (IL)‐6 may play a pathologic role in rheumatoid arthritis (RA) and chronic periodontitis (CP). The present study assesses IL‐6 receptor (IL‐6R) inhibition therapy on the periodontal condition of patients with RA and CP. Methods: The study participants were 28 patients with RA and CP during treatment with IL‐6R inhibitor, and 27 patients with RA and CP during treatment without IL‐6R inhibitor. Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers and immunoglobulin G against periodontopathic bacteria were examined after medication with IL‐6R inhibitor for 20.3 months on average (T1) and again 8 weeks later (T2). Results: No differences were observed between the groups in any parameter values at T1, except for serum IL‐6 levels. The anti–IL‐6R group showed a significantly greater decrease in gingival index, bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and serum levels of IL‐6 and matrix metalloproteinase (MMP)‐3 from T1 to T2 than the control group (P <0.05). A significant correlation was found between changes in serum anticyclic citrullinated peptide levels and those in PD and CAL in the anti–IL‐6R group (P <0.05), whereas both groups exhibited a significant association between changes in serum MMP‐3 levels and those in BOP (P <0.05). Conclusion: Changes in periodontal and serum parameter values were different between the patients with RA and CP during treatment with and without IL‐6R inhibitor.     

Dental Implants in Patients with Oral Lichen Planus: A Cross‐Sectional Study

Purpose: The main aim of this study was to evaluate the patients with oral lichen planus (OLP) and dental implants. Material and Methods: Three groups of 16 patients took part in the study. Group I patients had received dental implants and been diagnosed with OLP; Group II had not received implants but were diagnosed with OLP; Group III had implants but not OLP. Clinical observations and OLP symptoms were registered in each case. Periodontal pocket depth, implant mobility, bleeding upon probing, erythema, pain, and radiolucency around implants were measured. Patient quality of life was evaluated using OHIP 14. Results: Peri‐implant mucositis and peri‐implantitis were detected in 17.86% and 25% of the OLP‐implant group, while the control group with implants showed 18% and 16%. The implant survival rate in patients treated for OLP did not appear to differ from the survival rate among the general population. Quality of life was better among patients with implants and without OLP (p = .001). Conclusions: The results of the present study suggest that implants do not influence manifestations of OLP. OLP is not a risk factor for peri‐implantitis.     

8‐Hydroxy‐Deoxyguanosine Levels in Gingival Crevicular Fluid and Saliva in Patients With Chronic Periodontitis After Initial Periodontal Treatment

Background: This study evaluates the effects of initial periodontal treatment on the gingival crevicular fluid (GCF) and salivary levels of 8‐hydroxy‐deoxyguanosine (8‐OHdG) as a marker of oxidative deoxyribonucleic acid (DNA) damage in patients with chronic periodontitis (CP). Methods: At baseline, clinical parameters were determined and GCF and saliva samples were obtained from 24 patients with CP and 24 individuals with clinically healthy periodontium. GCF, saliva samples, and clinical periodontal measurements were repeated at day 10, 1 month, and 3 months following initial periodontal therapy in patients with CP. 8‐OHdG levels of GCF and saliva samples were investigated by using an enzyme‐linked immunosorbent assay. Results: Statistically significant higher 8‐OHdG levels of GCF and a significant decrease after initial periodontal therapy were determined in the CP group (P <0.001). A significant positive correlation was found between 8‐OHdG levels of GCF and clinical periodontal measurements (P <0.001). However, salivary levels of 8‐OHdG did not differ between groups or during initial periodontal therapy (P >0.05). Conclusions: This study reveals that DNA injury and oxidative stress increase in tissue cells and especially in periodontal pockets in patients with CP, and the periodontal treatment results in a significant decrease of 8‐OHdG levels in the GCF samples. To the best of our knowledge, this study evaluates for the first time, 8‐OHdG levels in GCF, which is shown to be more useful as a biomarker than saliva. 8‐OHdG was found to be important and may reveal the severity of periodontal disease and the effect of periodontal therapy.     

Cimetidine Reduces Interleukin‐6, Matrix Metalloproteinases‐1 and ‐9 Immunoexpression in the Gingival Mucosa of Rat Molars With Induced Periodontal Disease

Background: Histamine seems to act, via H₂ receptor, on inflammatory processes by stimulating interleukin (IL)‐6 and matrix metalloproteinase (MMP) release. As cimetidine is an H₂ receptor antagonist, the authors hypothesize that this antiulcer drug reduces IL‐6, MMP‐1, and MMP‐9 immunoexpression in gingiva with induced periodontal disease (PD). To confirm a possible modulatory role of IL‐6 on MMPs, the relationship between IL‐6/MMP‐1 and IL‐6/MMP‐9 immunoexpression was evaluated. Methods: Forty‐six male rats were distributed into the cimetidine group (CimG: received daily intraperitoneal injections of 100 mg/kg of body weight of cimetidine) or the saline group (SG). PD was induced by cotton ligature around the maxillary left first molars (PDSG and PDCimG). The right molars were used as controls (SG and CimG). After 7, 15, 30, and 50 days, maxillary fragments were processed for paraffin embedding or for transmission electron microscopy. Tartrate‐resistant acid phosphatase (TRAP)‐positive osteoclasts in the alveolar process surface and number of IL‐6, MMP‐1, and MMP‐9‐immunolabeled cells in the gingival mucosa were quantified. Statistical analyses were performed (P ≤0.05). Results: In PDSG and PDCimG, gingival mucosa exhibited few collagen fibers among numerous inflammatory cells. In PDCimG, the number of TRAP‐positive osteoclasts and IL‐6, MMP‐1, and MMP‐9‐immunolabeled cells was significantly lower than in PDSG at all periods. A positive correlation between IL‐6/MMP‐1 and IL‐6/MMP‐9 was detected in PDSG and PDCimG. Conclusion: Cimetidine decreases bone loss through reduction of osteoclast number and induces reduction of IL‐6, MMP‐1, and MMP‐9 immunoexpression, reinforcing the idea that the beneficial effect of cimetidine in PD may be due to reduction of IL‐6 immunolabeling in the inflamed gingival mucosa.     

Evaluation of MicroRNA‐146a and Its Targets in Gingival Tissues of Patients With Chronic Periodontitis

Background: MicroRNAs (miRNAs) are a group of small non‐coding RNAs that play an important role in the regulation of gene expression. miRNA‐146a (miR‐146a), a member of the miR‐146 family, is involved in the control of inflammation. Periodontitis is a set of chronic inflammatory disorders of the tissues surrounding the teeth that lead to the breakdown of alveolar bone and tooth loss. In this study, expression levels of miR‐146a and its targets, including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and IL‐6, are evaluated in human patients with chronic periodontitis (CP). Methods: The study population consisted of 10 healthy controls and 20 individuals with CP. For each participant, clinical parameters including probing depth and clinical attachment level were measured, and a gingival tissue sample was collected. Levels of miR‐146a, TNF‐α, IL‐1β, and IL‐6 were quantified using real‐time polymerase chain reaction. Results: Levels of miR‐146a were significantly higher in patients with CP (P <0.001). There was a positive correlation between levels of miR‐146a and clinical parameters (P <0.05). Elevated miR‐146a was accompanied by a significant reduction in TNF‐α and IL‐6 (P <0.001). Conclusions: Patients with CP had higher levels of miR‐146a than healthy individuals, accompanied by reduced levels of TNF‐α and IL‐6. A positive relationship between miR‐146a levels and clinical parameters suggests a pathophysiologic role of miR‐146a in CP.     

Meta‐Analysis of Association Between Interleukin‐1β C‐511T Polymorphism and Chronic Periodontitis Susceptibility

Background: Many studies have been conducted to explore the association between interleukin (IL)‐1β C‐511T polymorphism and risk of chronic periodontitis (CP) but with different or even contradictory results. A meta‐analysis was performed to further explore their association. Methods: PubMed, Chinese National Knowledge Infrastructure, and EMBASE were searched up to September 30, 2014 for relevant case‐control studies. Two authors (D‐YL and L‐YX) independently selected studies and extracted data from included studies. The meta‐analysis was performed using comprehensive meta‐analysis software. Results: Nineteen case‐control studies involving 2,173 patients with CP and 3,900 healthy controls were included. Using a random‐effects meta‐analysis model, a non‐significant association between IL‐1β C‐511T polymorphism and CP was identified (T versus C: odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.85 to 1.25; TT versus CC: OR = 1.03, 95% CI = 0.72 to 1.46; CT versus CC: OR = 0.96, 95% CI = 0.71 to 1.30; CT + TT versus CC: OR = 1.00, 95% CI = 0.74 to 1.34; TT versus CT + CC: OR = 1.05, 95% CI = 0.81 to 1.38), and sensitivity analysis indicated that the results were robust. Subgroup analyses also revealed a non‐significant association. No publication bias was detected. Conclusions: Based on currently available evidence, IL‐1β C‐511T polymorphism is not associated with the risk of developing CP. Additional research is warranted to further explore and confirm the association of genetic polymorphism and CP.     

Proinflammatory and Anti‐Inflammatory Cytokines in Gingival Crevicular Fluid and Serum of Patients With Rheumatoid Arthritis and Patients With Chronic Periodontitis

Background: The aim of this study is to evaluate proinflammatory and anti‐inflammatory cytokine levels in gingival crevicular fluid (GCF) and serum of rheumatoid arthritis (RA) and chronic periodontitis (CP) patients to assess whether cytokine profiles distinguish patients with RA and patients with CP while using healthy patients as background controls. Methods: A total of 49 patients, 17 patients with RA (three males and 14 females; mean age: 47.82 ± 10.74 years), 16 patients with CP (10 males and six females; mean age: 44.00 ± 7.00 years), and 16 controls (eight males and eight females; mean age: 28.06 ± 6.18 years) were enrolled. Patients with RA were under the supervision of rheumatologists; 15 of the patients with RA were being treated with methotrexate–sulfasalazine combined therapy, and two of the patients were being treated with leflunomid therapy. Periodontal parameters (plaque index, gingival index, probing depth, and clinical attachment level) were recorded. Interleukin (IL)‐1β, IL‐4, IL‐10, and tumor necrosis factor‐α (TNF‐α) were determined in GCF and IL‐1β and IL‐10 in serum by enzyme‐linked immunosorbent assay. Results: There were significant differences found among RA, CP, and control groups for all periodontal parameters (P <0.05). The total amount and concentration of GCF IL‐1 β, IL‐4, IL‐10, and TNF‐α were similar in RA and CP patients (P >0.05). Although the total amount and concentration of serum IL‐10 was not significantly different among the groups (P >0.05), serum IL‐1β was significantly lower in the RA group compared to CP patients and controls and was higher in GCF of the RA group compared to the CP group. Conclusions: Although clinical periodontal disease parameters indicated more severe periodontal disease in CP compared to RA patients, immunologic evaluation did not reveal consistent results regarding proinflammatory and anti‐inflammatory cytokine levels. This might be a result of the use of non‐steroidal anti‐inflammatory drugs and rheumatoid agents by patients with RA.     

Porphyromonas gingivalis HmuY‐Induced Production of Interleukin‐6 and IL‐6 Polymorphism in Chronic Periodontitis

Background: In chronic periodontitis (CP), the gene polymorphism of interleukin‐6 (IL‐6) to 174C/G has been associated with the altered production of this cytokine. The aim of this pilot study is to compare the allelic and genotypic frequencies in patients with CP with control individuals without periodontitis (NP) and to measure the production of IL‐6 by whole blood cells stimulated with Porphyromonas gingivalis HmuY protein. Methods: DNA was isolated from peripheral blood cells of 49 patients with CP and 60 control individuals classified as NP, and genotyping was performed by polymerase chain reaction using sequence‐specific primers. Whole blood cells from 29 patients with CP and 30 control individuals were stimulated for 48 hours with HmuY, and IL‐6 levels were measured using enzyme‐linked immunosorbent assay. Results: The proportion of individuals carrying the G allele at position –174 of the IL‐6 gene was higher in the group with CP (85.7%) than in the normal control group (73.3%; P <0.03). P. gingivalis HmuY‐induced production of IL‐6 was higher in the group with CP (P <0.05). Conclusions: Our findings suggest that P. gingivalis HmuY may be associated with increased IL‐6 production during CP. Furthermore, patients with periodontitis and individuals with higher HmuY‐induced production of IL‐6 show a high frequency of the G allele at position –174.     

Salivary Visfatin Concentrations in Patients With Chronic Periodontitis

Background: Visfatin, also known as pre‐B‐cell colony‐enhancing factor, is secreted from a variety of cells and is thought to have some proinflammatory and immunomodulating effects. It is indicated that serum/plasma levels of visfatin increase in a number of inflammatory disorders. The present study aims to evaluate salivary concentrations of visfatin in patients with chronic periodontitis (CP). Methods: Twenty patients with CP and 20 periodontally healthy individuals were enrolled in this study. For each patient, the values of clinical parameters, such as bleeding index, plaque index, probing depth, and clinical attachment level (CAL), were recorded. Whole saliva samples were collected, and concentrations of visfatin were evaluated using standard enzyme‐linked immunosorbent assay. Statistical analysis was performed using statistical software. Results: Visfatin was detectable in all samples. Salivary visfatin concentrations were significantly higher in the periodontitis group. In addition, there was a positive significant relationship between salivary visfatin concentrations and CAL in the periodontitis group. However, no significant association was observed between salivary visfatin levels and other periodontal parameters or body mass index. Conclusion: These results indicate that there is a relationship between salivary visfatin and CP; however, further studies are needed to confirm this finding.     

慢性牙周炎病变部位白细胞介素-8表达的初步研究

目的探讨牙龈组织中自细胞介素-8(IL-8)与慢性牙周炎的关系。方法采用免疫组化法检测32例牙龈组织样本(16例健康者，16例慢性牙周炎患者)，分析IL-8的检出率及IL-8分泌细胞在牙龈组织中的分布。结果慢性牙周炎患者中的IL-8的检出率均高于健康者，IL-8阳性细胞分布于牙龈的上皮和结缔组织中。结论研究结果提示IL-8参与了牙周炎的病理过程。     

Interleukin-6 in oral diseases: a review

Oral Diseases (2012) 18 , 236–243 Interleukin‐6 (IL‐6) is a pleomorphic cytokine involved in a number of physiologic and pathologic processes including response to trauma and infection and development and progression of inflammation and malignancy. IL‐6 is emerging as an important mediator and novel therapeutic target for chronic inflammatory diseases and cancer. The present study reviews the available evidence regarding the association between IL‐6 and a range of oral diseases including infections (periodontal disease and endodontic infections), immunologically mediated disorders (oral lichen planus and Sjögren’s syndrome) and malignancy (oral cancer and precancer). The role of common genetic variants of IL‐6 in determining individual susceptibility to certain oral diseases, as well as novel therapeutic strategies based on IL‐6 inhibition are also discussed.     

Prognostic Value of 8‐Hydroxy‐2′‐Deoxyguanosine and Human Neutrophil Elastase/α1‐Proteinase Inhibitor Complex as Salivary Biomarkers of Oxidative Stress in Chronic Periodontitis

Background: 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and human neutrophil elastase/α1‐proteinase inhibitor (HNE/α₁‐PI) complex have been regarded as reliable biomarkers of oxidative stress in inflammatory conditions. This study investigates whether the salivary levels of these two analytes may be linked with periodontal health status. Methods: One hundred ten patients with chronic periodontitis (CP) and 50 healthy controls were selected. Periodontal status was assessed by criteria based on probing depth, clinical attachment level, and extent and severity of periodontal breakdown. 8‐OHdG and HNE/α₁‐PI salivary levels were analyzed by enzyme‐linked immunosorbent assay. The association of these analytes with CP was analyzed individually and adjusted for confounding factors using a multivariate binary logistic regression model. Results: Significantly higher levels of both markers were detected in the CP group in comparison to controls. Weak‐to‐moderate positive significant correlations between salivary biomarkers and clinical parameters were observed. After binary logistic regression analysis, salivary levels of 8‐OHdG >17.35 ng/mL and HNE/α1‐PI complex >158.28 ng/mL were independently associated with disease status. Interaction effects among candidate prognostic variables were also noted. Conclusions: Increased salivary levels of 8‐OHdG and HNE/α₁‐PI complex may be strong, independent prognostic indicators of the amount and extent of oxidative stress–induced periodontal breakdown. In addition, unstimulated whole saliva samples might reflect a synergistic biologic interactive effect of HNE/α₁‐PI associated with the aging and smoking cumulative characteristics of periodontal damage.     

慢性牙周炎治疗前后龈沟液中PGE2、IL-6、IL-8的变化

目的检测慢性牙周炎患牙龈沟液(GCF)中PGE2、IL-6、IL-8在治疗前后的浓度,探讨评价牙周治疗效果的指标.方法选择20例牙周炎患牙,用超声波治疗仪进行龈下刮治,检查治疗前、治疗后4周龈沟出血指数(SBI),并收集治疗前后的GCF,用ELISA检测其中PGE2、IL-6、IL-8的浓度.结果治疗前后SBI分别为2.87±0.52和1.32±0.28,P＜0.01;PGE2 浓度为254.86±123.60和157.78±129.06 (ng/ml),P＜0.05;而IL-6、IL-8的浓度没有显著性差异.结论经过彻底的牙周治疗后,GCF中PGE2浓度明显降低,IL-6、IL-8降低没有统计学意义,提示作为牙周治疗效果评价的指标,PGE2较IL-6、IL-8等更为敏感.     

Interleukin‐6 and granulocyte‐macrophage colony‐stimulating factor in apical periodontitis: correlation with clinical and histologic findings of the involved teeth

Apical periodontitis is characterized by the presence of immunocompetent cells producing a wide variety of inflammatory mediators. Releasing cytokines with long‐range action, such as interleukin‐6 (IL‐6) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), apical periodontitis may induce changes in remote organs of the host. This study quantified the levels of IL‐6 and GM‐CSF in symptomatic and asymptomatic human periradicular lesions. Lesions were also characterized by size and histologic findings. Tissue samples were homogenized and supernatants were assayed using an enzyme‐linked immunosorbent assay (ELISA). Correlations between cytokine levels and characteristic features (as single variables) of the lesions were analysed. There was a trend for higher levels of IL‐6 and GM‐CSF in symptomatic than in asymptomatic lesions, but the difference was not significant. Levels also tended to be higher in large than in small lesions, in polymorphonuclear (PMN) cell‐rich than in PMN cell‐poor samples, and in epithelialized than in non‐epithelialized lesions. Significantly higher levels of IL‐6 (778.1 ± 220.5 pg/μg) and GM‐CSF (363.3 ± 98.4 pg/μg) were found in samples coincidentally possessing symptomatic and epithelialized features than in asymptomatic, small, PMN cell‐poor, non‐epithelialized lesions (IL‐6: 45.2 ± 13.1 pg/μg and GM‐CSF: 135.1 ± 26.4 pg/μg). These results suggest that symptomatic lesions containing epithelial cells represent an immunologically active stage of apical periodontitis, whereas asymptomatic, small, PMN cell‐poor, non‐epithelialized lesions represent healing apical lesions.