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.     

Evaluation of Biochemical Parameters and Local and Systemic Levels of Osteoactive and B‐Cell Stimulatory Factors in Gestational Diabetes in the Presence or Absence of Gingivitis

Background: Gestational diabetes mellitus (GDM) is defined as varying glucose intolerance, with first onset or recognition in pregnancy. This study evaluates clinical and biochemical parameters in a possible association between GDM and gingivitis. Methods: A total of 167 pregnant females was included in the study. There were 101 females with GDM and 66 females without GDM. Subgroups were created according to the presence or absence of gingival inflammation. Plaque index, bleeding on probing, and probing depth were recorded at four sites per tooth. Serum, saliva, and gingival crevicular fluid (GCF) levels of interleukin (IL)‐6, IL‐8, soluble receptor activator of nuclear factor‐kappa B ligand (sRANKL), osteoprotegerin (OPG), B‐cell activating factor (BAFF), and a proliferation‐inducing ligand (APRIL) were determined by enzyme‐linked immunosorbent assay. Data were analyzed by Kruskal‐Wallis and Mann‐Whitney U tests and Spearman correlation analysis. Results: Age and anthropometric indices were higher in the GDM than non‐GDM group (P <0.0001). Clinical periodontal recordings, serum BAFF, IL‐8, and saliva sRANKL levels were higher in the GDM group (P <0.05). Saliva IL‐6 level was higher in the GDM with gingivitis group than non‐GDM with gingivitis group (P = 0.044). Serum and GCF BAFF (P <0.0001), serum, saliva, and GCF APRIL (P <0.0001; P <0.0001; P = 0.032, respectively), GCF OPG (P = 0.036), and serum and saliva sRANKL (P <0.0001) were higher in the GDM with gingivitis group than GDM without gingivitis group. Conclusions: The inflammatory response seems to be more pronounced in females with GDM. The observed increase in both local and systemic levels of inflammatory cytokines may suggest an interaction between gingivitis and GDM.     

The Association Between Thalassemia Major and Periodontal Health

Background : The aim of this cross‐sectional study is to compare the local and systemic levels of soluble receptor activator of nuclear factor‐κB ligand (sRANKL), osteoprotegerin (OPG), a proliferation‐inducing ligand (APRIL), B‐cell activating factor (BAFF), interleukin (IL)‐6, and IL‐8 in biofluids of patients with thalassemia major (TM) with or without gingivitis. Methods: Seventy‐seven patients are included in this study (TM, n = 29; systemically healthy, n = 48). Gingival crevicular fluid (GCF), saliva, and serum levels of IL‐6, IL‐8, sRANKL, OPG, BAFF, and APRIL were determined by enzyme‐linked immunosorbent assay. Data were analyzed by appropriate non‐parametric or parametric statistical tests. Results: Median GCF, serum, and saliva levels for BAFF (P <0.001) and IL‐6 and IL‐8 (P <0.005) were higher in TM gingivitis than in systemically healthy gingivitis (P <0.001). GCF, serum, and saliva levels for APRIL, sRANKL, IL‐6, and IL‐8 were higher in TM than in systemically and periodontally healthy comparison groups (P <0.05). Positive correlations were found between bleeding on probing (BOP), plaque index (PI) scores, and GCF APRIL, serum sRANKL, serum OPG, and sRANKL concentrations in TM groups (P <0.05). Several significant positive correlations were found between BOP, PI scores, and biofluid parameters also in systemically healthy groups. Conclusion: TM may have a role in the underlying systemic hematologic condition and potentially affect gingival inflammation via dysregulation of lymphocytes and increased activation of osteoclasts.     

Gingival crevicular fluid and serum levels of APRIL,BAFF and TNF-alpha in rheumatoid arthritis and osteoporosis patients with periodontal disease

Background

This study was performed to evaluate gingival crevicular fluid (GCF) and serum levels of a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF) and compare this to differences between TNF-alpha levels in rheumatoid arthritis (RA), osteoporosis (OPR) and systemically healthy women with periodontal disease (SH).

Design

Gingival crevicular fluid (GCF) and serum samples were obtained before any periodontal intervention from 17 RA, 19 OPR patients and 13 SH women with periodontitis. Full-mouth clinical periodontal measurements were recorded. APRIL, BAFF and TNF-α levels were determined by ELISA. Statistical analysis was performed using multivariate analysis, ANOVA and Spearman correlation.

Results

Pocket depths differed in site-specific comparisons, but otherwise clinical measurements were similar in the three study groups. Multivariate least squares regression ANOVA adjusted for age and for plaque index indicated that total amounts of TNF-α and concentrations of TNF-α, BAFF and APRIL were significantly greater in the RA patients than in the SH group (p < 0.05), and GCF concentrations of BAFF were greater in OPR patients than in SH. Serum TNF-α and BAFF were significantly higher in the RA group compared to SH (p < 0.05) and serum TNF-α was greater in RA than in OPR (p < 0.05). APRIL and BAFF correlated with RANKL levels in GCF and serum (p < 0.05).

Conclusion

Despite long-term usage of anti-inflammatory drugs in the RA and OPR patients, increased TNF-family cytokines, might suggest that these patients have a propensity to overproduce these inflammatory mediators but whether this results from greater disease activity or contribute to greater disease activity remains moot.     

Increased Expression of Interleukin (IL)‐35 and IL‐17, But Not IL‐27, in Gingival Tissues With Chronic Periodontitis

Background: Interleukin (IL)‐35 plays an important role in immune regulation through the suppression of effector T‐cell populations, including T‐helper 17 (Th17) cells. Although Th17 cells and IL‐17 are involved in the pathogenesis of periodontitis, the level of IL‐35 in inflamed periodontal tissues is unclear. Here, IL‐35, IL‐17, and IL‐27 production/expression in gingival crevicular fluid (GCF) and human gingival tissue were investigated. Methods: GCF samples were collected from buccal (mesial, center, and distal) sites of teeth from patients with chronic periodontitis (CP) and healthy controls and were analyzed by enzyme‐linked immunosorbent assay for IL‐35 (periodontitis, n = 36; healthy, n = 30) and IL‐17 (periodontitis, n = 16; healthy, n = 13). Gingival tissue, including sulcus/pocket epithelium and underlying connective tissue, was collected from an additional 10 healthy participants and 10 patients with CP and were analyzed by quantitative polymerase chain reaction (qPCR) for Epstein Barr virus‐induced gene 3 (EBI3), IL12A, and IL17A. IL27p28 was also tested by qPCR. Results: IL‐35 and IL‐17 were significantly higher in GCF from patients with periodontitis than healthy participants (P <0.01, P <0.05, respectively). In both healthy participants and those with periodontitis, positive correlations were found among IL‐35 and probing depth and clinical attachment level (CAL) as well as between IL‐17 and CAL. EBI3, IL12A (components of IL‐35), and IL17A messenger RNA expression levels were significantly higher in inflamed gingival tissue than in healthy control tissues (P <0.05). IL27p28 was not detected in any sample, suggesting that IL‐27 is not produced in large quantities in periodontal tissue. Conclusion: IL‐35 and IL‐17, but not IL‐27, may play important roles in the pathogenesis of periodontitis.     

The Gingival Crevicular Fluid Levels of Interleukin‐11 and Interleukin‐17 in Patients With Aggressive Periodontitis

Background: The balance (ratio) of anti‐inflammatory and proinflammatory cytokines is thought to play an important role in the pathogenesis of chronic periodontitis. Moreover, the imbalance of anti‐inflammatory/proinflammatory cytokines may modulate disease progression in aggressive periodontitis (AgP). This study aims to investigate the levels of interleukin (IL)‐11 and IL‐17 and their ratio in gingival crevicular fluid (GCF) in patients with AgP. Methods: This study included 20 patients with generalized AgP (GAgP) and 18 healthy controls (HC). For each patient, the values of clinical parameters, such as gingival index, plaque index, probing depth, and clinical attachment level, were recorded. Levels of IL‐11 and IL‐17 in GCF samples were evaluated using enzyme‐linked immunosorbent assay. The values of clinical parameters, cytokine levels, and the ratios of cytokines were evaluated. Results: The values of all the clinical parameters were significantly higher in the GAgP group than in the HC group (P <0.001). The total amount and concentration of IL‐11 and the concentration of the IL‐17 and IL‐11/IL‐17 ratio were significantly lower in the GAgP group than in the HC group (P <0.001). The total amount of IL‐17 was not significantly different between the groups (P = 0.317) Conclusions: The IL‐11/IL‐17 ratio was decreased in the GAgP group because of the decreased IL‐11 levels. The IL‐11/IL‐17 axis and the link between IL‐17 and neutrophil function disorders in AgP should be investigated to clarify the role of the IL‐11/IL‐17 axis and its balance and imbalance in the pathogenesis of AgP.     

Is Interleukin‐17 Involved in the Interaction Between Polycystic Ovary Syndrome and Gingival Inflammation?

Background: Polycystic ovarian syndrome (PCOS) is a hormonal disorder of females of reproductive age that impacts their oral and systemic health. The aim of this study is to evaluate interleukin‐17A (IL‐17A), IL‐17F, IL‐17A/F, and IL‐17E (IL‐25) levels in gingival crevicular fluid (GCF), saliva, and serum of non‐obese females with PCOS and with either a clinically healthy periodontium or gingivitis. Methods: Thirty‐one females with PCOS, 30 females with PCOS and gingivitis, and 12 systemically and periodontally healthy females participated in the study. Clinical periodontal measurements, body mass index, and Ferriman‐Gallwey score (FGS) (a measure of hirsutism in females) were recorded. Circulating levels of sex hormones, cortisol, and insulin were also determined. Levels of IL‐17 cytokines were measured by enzyme‐linked immunosorbent assay. Results: The general linear model multivariate analysis, adjusting for age or plaque index, showed that the two groups with PCOS had higher concentrations of IL‐17A, IL‐17F, and IL‐17A/F in serum and higher levels of IL‐17A and IL‐17F in GCF and saliva but lower serum IL‐17E than systemically healthy females. Levels of IL‐17E were lowest in females with PCOS and gingivitis who also had the highest FGS. Serum IL‐17A and IL‐17F levels correlated positively with FGS and periodontal probing depth (all ρ >0.33; P <0.005). Serum IL‐17E showed the reverse relationship and also correlated negatively with IL‐17A (ρ >?0.28; P <0.05). Conclusions: IL‐17 levels are altered in non‐obese females with PCOS and may influence gingival inflammation. Additional studies are warranted to clarify the relationship between PCOS and gingivitis.     

Analysis of YKL‐40 Acute‐Phase Protein and Interleukin‐6 Levels in Periodontal Disease

Background: YKL‐40, a new acute‐phase protein, is shown to be elevated in inflammatory diseases, such as rheumatoid arthritis, type 2 diabetes mellitus, and coronary artery diseases. However, there is no data indicating a relationship between YKL‐40 and periodontal disease. Interleukin‐6 (IL‐6) is the major regulator of acute‐phase protein synthesis and one of the most studied inflammatory markers in periodontal disease. The purpose of the present study is to evaluate YKL‐40 and IL‐6 levels in gingival crevicular fluid (GCF) and serum of patients with periodontal disease and healthy individuals. Methods: Periodontally healthy individuals (n = 15), patients with gingivitis (n = 15), and patients with severe chronic periodontitis (CP) (n = 15) without any systemic disease were included in the study. Clinical measurements were recorded; GCF and blood samples were obtained from each participant. GCF and serum YKL‐40 and IL‐6 levels were analyzed by enzyme‐linked immunosorbent assay. Statistical analysis was performed by parametric and non‐parametric tests. Results: Total amounts of YKL‐40 and IL‐6 in GCF as well as serum YKL‐40 and IL‐6 levels were significantly higher in patients with gingivitis and CP compared with healthy controls (P <0.01). YKL‐40 levels in GCF and serum as well as serum IL‐6 levels were significantly higher in patients with CP compared with patients with gingivitis (P <0.01). Conclusions: YKL‐40 levels in GCF as well as serum YKL‐40 and IL‐6 levels increased from gingivitis to periodontitis. Within the limits of the present study, the YKL‐40 molecule might be a potential novel inflammatory marker of periodontal disease.     

Cytokines and bone-related factors in systemically healthy patients with chronic periodontitis and patients with type 2 diabetes and chronic periodontitis

Background: This study compares the levels of cytokines and bone‐related factors in the gingival crevicular fluid (GCF) of systemically healthy patients with chronic periodontitis (CP); and better‐controlled, and poorly controlled patients with type 2 diabetes and CP. Methods: Thirty‐seven patients with type 2 diabetes and CP and 20 systemically healthy patients with CP were enrolled in this study. The patients with diabetes mellitus were categorized as better‐controlled (n = 17; HbA_1c levels ≤8%) or poorly controlled (n = 20; glycated hemoglobin values >8%). Levels of tumor necrosis factor‐α, interleukin (IL)‐4, interferon (IFN)‐γ, IL‐23, IL‐17, soluble receptor activator of nuclear factor‐kappa B ligand (sRANKL), and osteoprotegerin (OPG) in GCF of diseased sites were analyzed by enzyme‐linked immunosorbent assay. Results: Type 2 diabetes mellitus, as a whole, upregulates the levels of OPG, sRANKL, IFN‐γ, IL‐17, and IL‐23 and downregulates the production of IL‐4 in sites with CP (P <0.05). Better‐controlled individuals exhibited the highest levels of IFN‐γ, whereas poorly controlled patients presented the highest levels of IL‐17 (P <0.05). There were no differences in the levels of tumor necrosis factor‐α, OPG, and IL‐23 among systemically healthy, better‐controlled, and poorly controlled patients with diabetes (P >0.05). Conclusions: Increased levels of proinflammatory cytokines and RANKL were observed in the GCF of patients with type 2 diabetes with CP, compared to patients without diabetes. In addition, poor or good glycemic status seems to modulate osteo‐immunoinflammatory mediators in a different manner.     

Level of Interleukin‐35 in Gingival Crevicular Fluid,Saliva, and Plasma in Periodontal Disease and Health

Background: A novel member of the interleukin (IL)‐12 family, IL‐35 is an important inhibitory cytokine released by regulatory T cells. The aim of this study is to evaluate gingival crevicular fluid (GCF), saliva, and plasma levels of IL‐35 in periodontal disease and health. Methods: Samples of GCF, whole saliva, and plasma were obtained from systemically healthy, non‐smoking individuals with gingivitis (n = 20) or chronic periodontitis (CP) (n = 20) and periodontally healthy individuals (n = 20). Full‐mouth clinical periodontal measurements, including probing depth (PD), bleeding on probing, gingival index, and plaque index (PI), were also recorded. Enzyme‐linked immunosorbent assay was used to determine IL‐35 levels in the samples. Data were tested statistically by analysis of variance and Pearson rank correlation test. Results: All clinical parameters were significantly higher in the CP group than the healthy and gingivitis groups (P <0.001). The GCF total amount of IL‐35 was significantly higher in the CP group than the other groups (P = 0.04), whereas the GCF concentration of IL‐35 was significantly higher in the healthy group than the other groups (P = 0.002). There were significant differences among the study groups in terms of salivary IL‐35 level (P <0.001), with the highest level observed in the healthy group and the lowest in the CP group. There was no statistical difference between groups in plasma levels of IL‐35 (P >0.05). There was a positive correlation between GCF total amount of IL‐35 and PD (r = 0.338, P = 0.03) and PI (r = 0.374, P = 0.005) parameters. Conclusions: IL‐35 could have an important role in suppressing periodontal inflammation and maintaining periodontal health. Additional studies are required to evaluate its role in periodontal diseases.     

Effect of Non‐Surgical Periodontal Treatment on Gingival Crevicular Fluid and Serum Endocan,Vascular Endothelial Growth Factor‐A,and Tumor Necrosis Factor‐Alpha Levels

Background: Periodontitis is a chronic inflammatory disease that occurs due to the interaction between pathogenic microorganisms and host defenses. Endocan is a proteoglycan secreted by endothelial cells under the control of inflammatory cytokines. Aims of the study are to determine serum and gingival crevicular fluid (GCF) endocan levels in the pathogenesis of periodontal diseases, supported with vascular endothelial growth factor (VEGF‐A) and tumor necrosis factor (TNF)‐alpha levels. This study additionally aims to evaluate correlation between GCF endocan levels, VEGF‐A, and TNF‐α levels with periodontal probing depth (PD). Methods: The study consists of two groups: group 1 (n = 20), healthy individuals; group 2 (n = 20), individuals with generalized chronic periodontitis (CP). Clinical measurements were recorded; GCF and serum samples were obtained from each participant before and 6 weeks after therapy. Levels of biomarkers were measured by enzyme‐linked immunosorbent assay. Intergroup comparisons of biochemical and clinical parameters were analyzed by Kruskal–Wallis/Bonferroni‐adjusted Mann–Whitney U test using statistical software. Results: Serum and GCF endocan, VEGF‐A, and TNF‐α levels were significantly higher in patients with CP than in healthy individuals (P <0.001) and decreased after treatment (P <0.03). A significant correlation was observed between GCF TNF‐α and PD (4 mm ≤ PD ≤5 mm and PD ≥6 mm). A significant relationship was found among GCF endocan and TNF‐α, VEGF‐A, CAL, and GI for all groups (P <0.05). Conclusions: Endocan and TNF‐α levels, both in GCF and serum, increased from health to periodontitis and decreased with non‐surgical periodontal treatment. Within the limits of the study, endocan may be considered as a potential inflammatory marker for periodontal disease.     

Gingival Crevicular Fluid Levels of Sclerostin,Osteoprotegerin, and Receptor Activator of Nuclear Factor‐κB Ligand in Periodontitis

Background: To investigate changes in the levels and relative ratios of sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor‐κB ligand (RANKL) in the gingival crevicular fluid (GCF) of patients with periodontitis after non‐surgical periodontal treatment. Methods: Fifty‐four individuals (27 healthy controls and 27 patients with chronic periodontitis [CP]) were enrolled in the study. Periodontitis patients received non‐surgical periodontal therapy. GCF sampling and clinical periodontal parameters were assessed before and 6 weeks after therapy. Sclerostin, OPG, and RANKL levels were measured by enzyme‐linked immunosorbent assay, and their relative ratios were calculated. Results: Total amounts and concentrations of sclerostin were significantly higher in patients with CP than in healthy individuals (P <0.025) and decreased after treatment (P <0.05). The RANKL/OPG ratio was significantly lower in healthy individuals than in patients with periodontitis before and after treatment (P <0.025), but no significant difference was observed in patients with periodontitis after treatment (P >0.05). The sclerostin/OPG and sclerostin/RANKL ratios were significantly lower in healthy individuals than in patients with periodontitis before and after treatment (P <0.025) and decreased in patients with periodontitis after treatment (P <0.05). Conclusions: The GCF sclerostin level may be more reliable than the RANKL/OPG ratio as a diagnostic and prognostic marker of periodontal disease and treatment outcome. Regulation of sclerostin levels may aid the development of new therapeutic strategies for the treatment of periodontal disease.     

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.     

Short‐Term Effects of Non‐Surgical Periodontal Treatment on the Gingival Crevicular Fluid Cytokine Profiles in Sites With Induced Periodontal Defects: A Study on Dogs With and Without Streptozotocin‐Induced Diabetes

Background: The aim of this study is to assess the short‐term effects of non‐surgical periodontal therapy (NSPT) on the gingival crevicular fluid (GCF) cytokine profile in sites with standardized periodontal bony defects in beagle dogs with and without diabetes. Methods: Four beagle dogs with streptozotocin (STZ)‐induced diabetes and four healthy dogs were included. Fasting blood glucose levels were measured using a glucometer. In all animals, a 3‐walled bony defect was created on the mesial surface of the second premolar and first molar in all quadrants. After 12 weeks, all animals underwent weekly NSPT for 3 weeks. Baseline and post‐NSPT GCF samples were collected, and levels of interleukin (IL)‐1, IL‐1β, IL‐6, IL‐8, and tumor necrosis factor (TNF)‐α were measured using enzyme‐linked immunosorbent assay. Statistical analyses were performed using a software program, and P values <0.05 were considered statistically significant. Results: Mean fasting blood glucose levels were significantly higher in dogs with induced diabetes than those without diabetes (P <0.01). At baseline, mean IL‐6 (P <0.01) and IL‐8 (P <0.05) levels were higher in dogs with diabetes than those without diabetes. A significant reduction in levels of IL‐1, IL‐1β, IL‐6, IL‐8, and TNF‐α was noted in dogs without diabetes 1 week after NSPT. However, this significant reduction (P <0.05) only appeared 2 weeks after NSPT in dogs with diabetes. Conclusions: NSPT reduces GCF levels of proinflammatory cytokines in dogs with and without STZ‐induced diabetes; however, chronic hyperglycemia seems to retard the effect of NSPT on GCF cytokine concentration.     

Chemerin as a Novel Crevicular Fluid Marker of Patients With Periodontitis and Type 2 Diabetes Mellitus

Background: The objectives of the present study are to: 1) determine whether gingival crevicular fluid (GCF) chemerin is a novel predictive marker for patients with chronic periodontitis (CP) with and without type 2 diabetes mellitus (t2DM); 2) analyze the relationship between chemerin and interleukin (IL)‐6 in periodontally healthy individuals and in patients with CP and with and without t2DM; and 3) evaluate the effect of non‐surgical periodontal therapy on GCF chemerin levels. Methods: Eighty individuals were split into four groups: 20 who were systemically and periodontally healthy (CTRL), 20 with t2DM and periodontally healthy (DM‐CTRL), 20 systemically healthy with CP (CP), and 20 with CP and t2DM (DM‐CP). Individuals with periodontitis were treated with non‐surgical periodontal therapy. GCF sampling procedures and clinical periodontal measures were performed before and 6 weeks after treatment. Enzyme‐linked immunosorbent assay was used to measure chemerin and IL‐6 levels. Results: Greater values for GCF chemerin and IL‐6 levels were found in CP groups than in periodontally healthy groups, in DM‐CP than in CP, and in DM‐CTRL than in CTRL (P <0.008). GCF chemerin and IL‐6 levels decreased following therapy in CP groups (P <0.02). A comprehensive overview of all groups showed a statistically significant positive correlation of chemerin with IL‐6, glycated hemoglobin, sampled‐site clinical attachment level, and gingival index (P <0.05). Conclusions: In this study, periodontitis and t2DM induced aberrant secretion of chemerin, and non‐surgical periodontal therapy influenced the decrease of GCF chemerin levels in patients with CP with and without t2DM. Furthermore, it suggests GCF chemerin levels may be considered a potential proinflammatory marker for diabetes, periodontal disease, and treatment outcomes.     

A Cross‐Sectional Assessment of Biomarker Levels Around Implants Versus Natural Teeth in Periodontal Maintenance Patients

Background: Recent studies point to the clinical utility of using peri‐implant sulcular fluid (PISF) as a valuable diagnostic aid for monitoring peri‐implant tissue health. The objectives of this study are to determine the levels of key biomarkers in PISF in periodontal maintenance participants and compare them with their corresponding levels in gingival crevicular fluid (GCF) obtained from the same participants. Methods: PISF and GCF were collected from an implant and a contralateral natural tooth after the clinical examination of 73 participants. The levels of interleukin (IL)‐1α, IL‐1β, IL‐6, IL‐8, IL‐10, IL‐12, IL‐17A, tumor necrosis factor (TNF)‐α, C‐reactive protein, osteoprotegerin, leptin, and adiponectin were determined using multiplex proteomic immunoassays. The correlation of biomarker concentrations between GCF versus PISF, within GCF or PISF, and with several covariates (age, brushing frequency, days since professional cleaning, probing depth [PD], and plaque index) were also determined. Results: Significantly higher levels of IL‐17A (P = 0.02) and TNF‐α (P = 0.03) were noted in PISF when compared with their levels in GCF. Significant positive correlations were noted between the concentrations of cytokines in PISF versus their levels in GCF. Among the covariates, a significant positive correlation was noted between mean PDs around implants and levels of IL‐1β (P <0.05) and IL‐8 (P <0.05) in PISF. Conclusion: The results of this study point to the differential expression of specific biomarkers in GCF versus their levels in PISF in periodontal maintenance patients, which is critical information before establishing PISF as a diagnostic fluid to monitor peri‐implant health.     

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.     

Interleukin‐6 Family of Cytokines in Crevicular Fluid of Renal Transplant Recipients With and Without Cyclosporine A–Induced Gingival Overgrowth

Background: Interleukin (IL)‐6 family of cytokines, including IL‐6, oncostatin M (OSM), leukemia inhibitory factor (LIF), and IL‐11, have fibrogenic features. The current study determines gingival crevicular fluid (GCF) levels of fibrosis‐related IL‐6–type cytokines in cyclosporine A (CsA)–induced gingival overgrowth (GO). Methods: Eighty non‐smokers were included (40 CsA‐medicated renal transplant patients with GO [GO + ; n = 20] or without GO [GO?; n = 20], 20 individuals with gingivitis, and 20 healthy participants). Probing depth and plaque, papilla bleeding, and hyperplastic index scores were recorded. GCF samples were obtained from the mesio‐buccal aspects of two teeth. GCF IL‐6, IL‐1β, OSM, LIF, and IL‐11 levels were analyzed by enzyme‐linked immunosorbent assay. Results: The GO+ and GO? groups had higher IL‐6 total amounts than the healthy group (P <0.008). IL‐1β total amounts in the GO+ group were significantly higher than in both the healthy and GO? groups (P <0.008). OSM total amount was elevated in the GO+ and GO? groups compared with both the gingivitis and healthy groups (P <0.008). All groups had similar LIF and IL‐11 total amounts (P >0.008). Moderate positive correlations were detected among IL‐6, IL‐1β, OSM, and IL‐11 total amount in GCF and clinical parameters (P <0.05). Conclusions: IL‐6 and OSM increases in GCF as a result of CsA usage or an immunosuppressed state irrespective of the severity of inflammation and the presence of GO. The IL‐6 family of cytokines might not be directly involved in biologic mechanisms associated with CsA‐induced GO. Lack of an association between assessed IL‐6 cytokines and CsA‐induced GO might indicate distinct effects of these cytokines on fibrotic changes of different tissues.     

Evaluation of t-PA, PAI-2, IL-1beta and PGE(2) in gingival crevicular fluid of rheumatoid arthritis patients with periodontal disease

AIMS: This study was undertaken to compare periodontal conditions, gingival crevicular fluid (GCF) levels of tissue-type plasminogen activator (t-PA), its inhibitor plasminogen activator inhibitor-2 (PAI-2), interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)) in rheumatoid arthritis (RA) patients and control groups. METHODS: Twenty-three RA patients, 17 systemically healthy patients with periodontal disease (PD), and 17 systemically and periodontally healthy subjects were recruited. GCF samples were obtained from two single-rooted teeth. Full-mouth clinical periodontal measurements were recorded at six sites/tooth. GCF samples were analysed using relevant ELISA kits. Data were tested statistically by appropriate tests. RESULTS: Total amounts of t-PA, PAI-2 and PGE(2) in GCF samples of the healthy control group were significantly lower than the other groups (p<0.05). The RA group exhibited a higher total amount of t-PA in GCF samples than the PD group (p<0.05). PAI-2, IL-1beta and PGE(2) total amounts were similar in RA and PD groups (p>0.05). CONCLUSION: The coexistence of RA and periodontitis does not seem to affect clinical periodontal findings or systemic markers of RA. Similar inflammatory mediator levels in RA and PD groups, despite the long-term usage of corticosteroids, non-steroidal anti-inflammatory drugs, suggest that RA patients may have a propensity to overproduce these inflammatory mediators.     

Effect of Non‐Surgical Periodontal Treatment on Visfatin Concentrations in Serum and Gingival Crevicular Fluid of Patients With Chronic Periodontitis and Type 2 Diabetes Mellitus

Background : This study aims to assess visfatin concentrations in serum and gingival crevicular fluid (GCF) and investigate this relationship in patients with type 2 diabetes mellitus (T2DM) and chronic periodontitis (CP) before and after non‐surgical periodontal treatment. Methods: Fifty‐four patients with T2DM and CP were recruited. The patients were randomly divided into two groups: treatment and control. Serum and GCF visfatin concentrations and glycated hemoglobin (HbA1c) levels were measured by enzyme‐linked immunosorbent assay at different time points (at baseline and 3 and 6 months after non‐surgical periodontal treatment). Results: Serum and GCF visfatin concentrations showed no significant differences between the groups at baseline (t test, P >0.05). A significant decline of visfatin in the treatment group was found in serum and GCF 3 months after non‐surgical periodontal treatment (t test, P <0.01). Baseline and 3‐month HbA1c levels were not significantly different, but at 6 months, a statistically significant difference was detected (t test, P >0.05). Conclusions: The data suggest that non‐surgical periodontal treatment is helpful for glucose control, an effect that may be associated with reduced visfatin in patients with T2DM and periodontitis. Furthermore, the data suggest that visfatin may be considered an inflammatory marker for periodontal diseases.