Is There an Interaction Between Polycystic Ovary Syndrome and Gingival Inflammation?

Background: The aim of this study is to evaluate the gingival crevicular fluid (GCF), saliva, and serum concentrations of tumor necrosis factor‐α (TNF‐α), TNF‐α receptor‐1 (TNF‐αR1), TNF‐αR2, and interleukin‐6 (IL‐6) in non‐obese females with polycystic ovary syndrome (PCOS) and either clinically healthy periodontium or gingivitis. Methods: Thirty‐one females with PCOS and healthy periodontium, 30 females with PCOS and gingivitis, and 12 systemically and periodontally healthy females were included in the study. GCF, saliva, and serum samples were collected, and clinical periodontal measurements, body mass index, and Ferriman‐Gallwey score (FGS) were recorded. Sex hormones, cortisol, and insulin levels were measured. TNF‐α, TNF‐αR1, TNF‐αR2, and IL‐6 were determined by enzyme‐linked immunosorbent assay. Kruskal‐Wallis followed by Bonferroni‐corrected post hoc Mann‐Whitney U tests were used to analyze the data. Results: The PCOS + gingivitis group revealed significantly higher GCF, saliva, and serum IL‐6 concentrations than the PCOS + healthy group (P <0.0001). The two PCOS groups exhibited significantly higher saliva TNF‐α concentrations than the control group (P = 0.024 and P = 0.013, respectively). The FGS index was significantly higher in the PCOS + gingivitis group than the PCOS + healthy group (P = 0.030). The PCOS + gingivitis group revealed significantly higher insulin concentration than the PCOS + healthy and control groups (P = 0.014 and P <0.0001, respectively). Serum TNF‐α, TNF‐αRs, and serum, GCF, and salivary IL‐6 levels correlated with the clinical periodontal measurements. Conclusions: PCOS and gingival inflammation appear to act synergistically on the proinflammatory cytokines IL‐6 and TNF‐α. Thus, PCOS may have an impact on gingival inflammation or vice versa. Additional studies are warranted to clarify the possible relationship between PCOS and periodontal disease.     

Interleukin-33 levels in gingival crevicular fluid, saliva, or plasma do not differentiate chronic periodontitis

Background: This study investigates whether gingival crevicular fluid (GCF), saliva, and plasma levels of interleukin‐33 (IL‐33) can differentiate individuals with chronic periodontitis from individuals with healthy periodontium. Methods: GCF, whole saliva, and plasma samples together with full‐mouth clinical periodontal recordings were obtained from 32 otherwise healthy, non‐smoker chronic periodontitis individuals and 25 systemically and periodontally healthy, non‐smoker individuals. IL‐33 levels in the biofluid samples were determined by enzyme‐linked immunosorbent assay. Data were tested statistically by Mann‐Whitney U test. Results: The GCF concentrations of IL‐33 were significantly lower in chronic periodontitis individuals than in healthy individuals (P <0.0001), whereas the total amounts in GCF samples were similar (P >0.05). The salivary and plasma contrations of IL‐33 were indifferent in the two study groups (P >0.05). Conclusions: According to the present findings, the GCF, saliva or plasma levels of IL‐33 could not differentiate chronic periodontitis individuals and periodontally healthy individuals. Larger‐scale intervention studies may better clarify this issue.     

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.     

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.     

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.     

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.     

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.     

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.     

Gingival Crevicular Fluid,Serum Levels of Receptor Activator of Nuclear Factor‐κB Ligand,Osteoprotegerin, and Interleukin‐17 in Patients With Rheumatoid Arthritis and Osteoporosis and With Periodontal Disease

Background: This study is performed to evaluate gingival crevicular fluid (GCF) and serum levels of soluble receptor activator of nuclear factor‐κB ligand (sRANKL), interleukin (IL)‐17A, IL‐17E, IL‐17F, IL‐17A/F, and osteoprotegerin (OPG) in women with rheumatoid arthritis (RA), osteoporosis (OPR), and those who are systemically healthy (SH), all with periodontal disease. Methods: GCF and serum samples were obtained before any periodontal intervention from 17 women with RA, 19 with OPR, and 13 who were SH with periodontitis. Full‐mouth clinical periodontal measurements were recorded. sRANKL, OPG, and IL‐17 levels were determined by enzyme‐linked immunosorbent assay. Results: Clinical periodontal measurements were similar in the three study groups. Although the total amounts of GCF albumin, OPG, IL‐17A, and IL‐17A/F were similar in the study groups, there were statistically significant differences in GCF concentrations of sRANKL, OPG, IL‐17A, IL‐17E, IL‐17F, and IL‐17A/F. The sRANKL/OPG ratios were significantly higher in the RA group than in the OPR and SH groups (P <0.05). Serum sRANKL, sRANKL/OPG, and IL‐17A/IL‐17E ratios were significantly higher, whereas OPG concentrations were significantly lower in the RA group compared to other groups (P <0.05). Serum IL‐17A concentrations were significantly higher in the RA and OPR groups than in the SH group (P <0.05). Conclusion: Increased inflammatory mediator levels in patients with RA, despite the long‐term use of various anti‐inflammatory drugs, suggest that these patients may have a propensity to overproduce these inflammatory mediators.     

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.     

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.     

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.     

The Role of Factors Associated With Apoptosis in Assessing Periodontal Disease Status

Background: Little is known about the release of apoptotic proteins during periodontal breakdown. This pilot study investigates the presence of factors associated with apoptosis in serum, saliva, and gingival crevicular fluid (GCF) and their association with periodontal disease severity and activity. Methods: GCF, whole saliva, and serum were obtained from 47 adult patients with chronic periodontitis (CP) and 10 healthy controls. Clinical measurements, including probing depth (PD), clinical attachment level (CAL), and radiographs, were used to classify patients into healthy, mild, and moderate/severe CP groups. Enzyme‐linked immunosorbent assays were used to measure apoptosis or DNA fragmentation in GCF and active caspase‐3, soluble Fas (sFas), and sFas ligand (sFasL) in saliva and serum. Western immunoblotting was used to detect Fas, FasL, sFasL, and caspase‐3 expression in GCF. Results: DNA fragmentation was positively correlated with PD and CAL regardless of patient disease status (P <0.001). sFas and sFasL were present in saliva and serum, but there were no differences between groups. In GCF, the greater odds of detecting Fas, sFasL, and caspase‐3 increased with increasing PD and CAL (P <0.05). In addition, sites with inflammation and PD ≥5 mm had significantly greater odds of exhibiting Fas, sFasL, and caspase‐3 expression compared with sites without inflammation and PD <5 mm (P <0.05). Caspase‐3 was not detected in saliva or serum. At the patient level, only FasL and disease status were significantly correlated (P <0.05). Conclusion: Factors associated with apoptosis were detected in GCF in patients with CP.     

Effect of periodontal treatment on IL-1beta, IL-1ra, and IL-10 levels in gingival crevicular fluid in patients with aggressive periodontitis

Aim: The aim of this study was to examine the effect of phase I periodontal treatment on the levels of interleukin (IL)‐1β, IL‐1ra, and IL‐10 in gingival crevicular fluid (GCF) in patients with generalized aggressive periodontitis (G‐AgP). Material and Methods: Data were obtained from 15 patients with aggressive periodontitis and 15 healthy controls. GCF was collected from at least four pre‐selected sites (one shallow, at least two moderate, or at least one deep pockets) in patients with G‐AgP. In the healthy group, GCF samples were collected from one site. The cytokine levels were determined by an enzyme‐linked immunosorbent assay. Probing depth, clinical attachment level (CAL), gingival and plaque indices, and bleeding on probing were measured. The GCF sampling and clinical measurements were recorded at baseline and 6 weeks later after periodontal treatment. Results: IL‐1β levels were significantly higher at the moderate and deep pocket sites compared with the shallow sites (p<0.05). After periodontal therapy, IL‐1β levels were significantly reduced in the moderate and deep pocket sites (p<0.05). IL‐1ra levels at baseline of the moderate and deep pocket sites were significantly lower than the control sites (p<0.05). IL‐10 levels were similar in all pockets and did not change after periodontal therapy. Conclusions: The periodontal treatment improves the clinical parameters in G‐AgP, and this improvement is evident in deep pocket sites for pocket depth and CAL values. These results confirm that IL‐1β is effective for evaluating the periodontal inflammation and can thus be used as a laboratory tool for assessing the activity of periodontal disease.     

Longitudinal Comparison of Cytokines in Peri‐Implant Fluid and Gingival Crevicular Fluid in Healthy Mouths

Background: Peri‐implant and gingival tissues provide important sealing and protective functions around implants and teeth, but comparisons of the immunologic responses of these tissues after implant placement have not been conducted. Cytokine levels were measured in peri‐implant crevicular fluid (PICF) and gingival crevicular fluid (GCF) as surrogate measures of immune function at subcrestally placed dental implants and healthy periodontal sites during a 1‐year monitoring period. Methods: A total of 27 dental implants were placed subcrestally in 21 periodontally healthy patients (mean age: 49.0 ± 13.4 years). Repeated clinical and cytokine measurements were obtained over 12 months. GCF and PICF samples were collected and analyzed by cytokine microarray. Data were examined by non‐parametric analysis of variance. Results: Plaque and bleeding indices were similar among all patients (P >0.05) at baseline. During 1 year of monitoring, the mean volumes of PICF and GCF were similar (P >0.05). The levels of interleukin (IL)‐4, ‐6, ‐10, and ‐12p70, tumor necrosis factor‐α, and interferon‐γ in GCF and PICF were not significantly different and did not vary over time (P >0.05). The levels of IL‐1α were higher in GCF than PICF at 1, 2, 6, and 12 months, as were the levels of IL‐8 at 1, 2, 4, 6, and 12 months (P <0.001). Transforming growth factor‐β1 in PICF and GCF exhibited time‐dependent increases, and vascular endothelial growth factor was reduced at 1 year without differences between PICF and GCF (P >0.05). Conclusion: Within the limitations of this study design, it can be concluded that after subcrestal implant placement, the immune response of peri‐implant and periodontal tissues, as assessed by cytokine levels in PICF and GCF, is similar.     

Does Obstructive Sleep Apnea Increase the Risk for Periodontal Disease? A Case‐Control Study

Background: A possible association between periodontitis and obstructive sleep apnea (OSA) has been suggested. The aim of this study is to compare periodontitis prevalence between controls and patients with OSA by assessing clinical periodontal parameters and gingival crevicular fluid (GCF) levels of interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, and high‐sensitive C‐reactive protein (hs‐CRP); serum hs‐CRP was also sampled. Methods: A case‐control study was performed that included 163 individuals: 83 individuals (18 females and 65 males) with OSA and 80 non‐OSA individuals (23 females and 57 males) as controls. The test group was classified according to OSA severity. Clinical periodontal measurements were recorded, and GCF samples were collected. GCF hs‐CRP, IL‐lβ, and TNF‐α levels were analyzed using an enzyme‐linked immunosorbent assay method. Serum hs‐CRP was measured by latex‐enhanced immunoturbidimetric assay. Results: Prevalence of periodontitis in the OSA group (96.4%) was significantly higher than in the control group (75% [P <0.001]). Severe periodontitis prevalence was higher in the OSA group than control group. All periodontal clinical parameters and GCF IL‐lβ concentrations were significantly higher in patients with OSA than in controls (P = 0.001). No significant differences were found between the mild OSA and moderate‐to‐severe OSA groups. Additionally, there was no significant difference in GCF TNF‐α and hs‐CRP levels between the groups (P >0.05). Serum hs‐CRP levels were significantly higher in patients with OSA. A significant correlation was found between GCF IL‐1β and all clinical parameters. Conclusions: Results demonstrated higher prevalence of periodontitis and higher levels of GCF IL‐1β and serum hs‐CRP in patients with OSA. However, there is still a need for randomized clinical trials testing oral care interventions.     

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.     

Subantimicrobial-dose doxycycline and cytokine-chemokine levels in gingival crevicular fluid

Background: The present randomized, double‐masked, placebo‐controlled, parallel‐arm study examines the impact of adjunctive subantimicrobial‐dose doxycycline (SDD) on the local inflammatory response through cytokine and chemokine levels in gingival crevicular fluid (GCF) samples from patients with chronic periodontitis. Methods: Forty‐six patients with chronic periodontitis received scaling and root planing with or without adjunctive SDD. GCF samples were collected and clinical parameters including probing depth, clinical attachment level, gingival index, and plaque index were recorded every 3 months for 12 months. GCF tumor necrosis factor‐α, interleukin (IL)‐6, IL‐4, IL‐10, IL‐13, IL‐17, macrophage inhibitory protein 1α, macrophage inhibitory protein 1β, monocyte chemoattractant protein 1, and regulated on activated normal T‐cell expressed and secreted protein levels were determined by xMAP multiplex immunoassay. Results: Significant improvements were observed in all clinical parameters in both groups over 12 months (P <0.0125), whereas the SDD group showed significantly better reduction in gingival index, probing depth, and gain in clinical attachment compared to the placebo group (P <0.05). Decrease in IL‐6 in the SDD group was significantly higher compared to the placebo group at 6 and 9 months in deep pockets (P <0.05), whereas tumor necrosis factor‐α was significantly reduced in moderately deep pockets (P <0.05). SDD resulted in a stable IL‐4 and IL‐10 response while reducing the monocyte chemoattractant protein 1 levels at 3 months (P <0.05). Conclusions: These results show that SDD, as an adjunct to non‐surgical periodontal therapy, stabilizes the inflammatory response by promoting the suppression of proinflammatory cytokines and increasing the anti‐inflammatory cytokines. The chemokine activity would account for the regulation of the inflammatory response to SDD therapy.     

Levels of interleukin-21 in patients with untreated chronic periodontitis

Background: A growing body of evidence suggested that interleukin (IL)‐21 enhances the effector phase during T‐cell responses. The aim of our study is to determine the levels of IL‐21 in periodontal sites from patients with chronic periodontitis and controls. Methods: The population studied consisted of 34 patients (15 with chronic periodontitis and 19 healthy patients). Twenty samples (10 gingival crevicular fluid [GCF] and 10 gingival biopsies) were collected from each group before the patients with periodontitis received periodontal treatment. Total protein concentrations were measured in all samples; the presence of IL‐21 was confirmed by immunohistochemistry and Western blot, and IL‐21 levels were quantified through an enzyme‐linked immunosorbent assay. Statistical analyses were performed using statistical software. Data were expressed as patient means ± SDs or medians (interquartile ranges) by using the χ², Student t, and Mann‐Whitney U tests. Results: GCF IL‐21 was mainly detected in patients with chronic periodontitis (P <0.05). Levels of IL‐21 in gingival tissues were significantly higher in patients with chronic periodontitis compared to healthy individuals (P <0.05). The Western blot and immunohistochemical staining confirmed the presence of IL‐21 in periodontal tissues and GCF. Conclusion: IL‐21 was highly expressed in patients with chronic periodontitis, especially in gingival biopsies; therefore, IL‐21 might play a role in the T‐cell response.     

Dental plaque, gingival inflammation, and elevated levels of interleukin-6 and cortisol in gingival crevicular fluid from women with stress-related depression and exhaustion

BACKGROUND: The aim of the present study was to investigate the importance of stress for the development of periodontitis by comparing oral health status, proinflammatory markers, and cortisol in gingival crevicular fluid (GCF) and saliva in patients with stress-related mental depression and controls. METHODS: The participants consisted of 43 women with stress-related depression and exhaustion (Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV], with a mean age of 42.0 (+/- 9.3 SD) years, and 29 controls, with a mean age of 54.5 (+/- 2.9 SD) years. Clinical examination included the assessment of dental plaque, gingival inflammation (GI), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and number of teeth. GCF was collected with an intracrevicular washing technique from four sites in each subject. Interleukin (IL)-1beta, IL-6, and matrix metalloproteinase-9 were determined with enzyme-linked immunosorbent assay and cortisol with radioimmunoassay (125I RIA). Analysis of covariance (one-way covariance analyses) was used to remove the influence of age and smoking. RESULTS: The amount of plaque was significantly higher in patients compared to controls (P<0.003). The patients had an average GI of 1.53 (+/-0.13 SD) compared to 0.89 (+/- 0.10 SD) for the controls (P< 0.001). The levels of cortisol in GCF was significantly higher in patients than in controls, 3.46 nmol/l (+/- 3.25 SD) and 0.30 nmol/l (+/- 0.25 SD), respectively (P<0.001), whereas cortisol in saliva did not differ between groups. The levels of IL-6 in GCF were significantly higher in the patients than in controls (P<0.05). CONCLUSION: Women with stress-related depression and exhaustion had more plaque accumulation, GI and increased levels of IL-6 and cortisol in GCF compared to normal controls, suggesting that depression might affect immune function, which could lead to impaired periodontal health.