Proinflammatory cytokine levels in hyperlipidemic patients with periodontitis after periodontal treatment

Oral Diseases (2012) 18 , 299–306 Objective: The aim of this study was to evaluate the effects of periodontal treatment on serum and gingival crevicular fluid (GCF) proinflammatory cytokine levels in hyperlipidemic patients with periodontitis. Materials and Methods: Fifty‐two patients with hyperlipidemia and periodontitis and 28 systemically healthy controls with periodontitis (C) were included in the study. Hyperlipidemic groups were divided into two groups as suggested diet (HD) and prescribed statin (HS). The clinical periodontal parameters, fasting venous blood, and GCF samples were obtained, and serum tumor necrosis factor‐alpha (TNF‐α), interleukin (IL) 1‐beta, and IL‐6 levels were evaluated at baseline and at 3 months follow‐up (3MFU) after the completion of the non‐surgical periodontal treatment that included scaling and root planning. Results: Percentage of bleeding on probing was significantly higher in the HS group than both the HD and C groups. In the HD and HS groups, there were significant decreases in serum IL‐6 and GCF TNF‐α levels between the 3MFU and baseline. A significant decrease was also found in GCF IL‐6 at the end of the study period in the HS group. Conclusion: The combination of the periodontal therapy and antilipemic treatment may provide beneficial effects on the metabolic and inflammatory control of hyperlipidemia.     

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.     

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.     

Cytokine profile in the gingival crevicular fluid of rheumatoid arthritis patients with chronic periodontitis

The aim was to assess the cytokine profile in the gingival crevicular fluid (GCF) of rheumatoid arthritis (RA) patients with chronic periodontitis (CP). Databases were searched from 1991 to August 2013 using a combination of various keywords. Eight studies were included. The GCF concentrations of interleukin (IL)‐1β, IL‐4, IL‐10, matrix metalloproteinase (MMP)‐8, MMP‐13 and tumor necrosis factor‐alpha (TNF‐α) were reported to be higher in patients with RA than in healthy controls (HC) without CP. In one study, TNF‐α levels in GCF were significantly higher in HC than in RA patients receiving anti‐TNF‐α therapy. One study reported no significant difference in GCF TNF‐α levels among RA patients and HC regardless of anti‐TNF‐α therapy. One study reported no difference in IL‐1β and prostaglandin E₂ levels among RA patients and HC with CP. Raised levels of proinflammatory cytokines are exhibited in the GCF of RA patients with CP.     

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.     

Saliva and Serum Levels of B‐Cell Activating Factors and Tumor Necrosis Factor‐α in Patients With Periodontitis

Background: B‐lymphocytes play a central and critical role in the adaptive immune response against invading pathogens. This study evaluates saliva and serum levels of APRIL (a proliferation‐inducing ligand), B‐cell activating factor (BAFF), tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐6, and IL‐10 in patients with chronic periodontitis (CP) or aggressive periodontitis (AgP) and periodontally healthy individuals. Methods: Twenty‐five patients with AgP, 20 patients with CP, and 20 periodontally healthy individuals were included. Smoking status was recorded, and all individuals were divided into non‐smokers and smokers. Saliva and serum samples were collected before clinical periodontal measurements. APRIL, BAFF, TNF‐α, IL‐6, and IL‐10 levels in serum and saliva samples were determined by enzyme‐linked immunosorbent assay. Statistical analysis was performed using multivariate analysis of variance and bivariate correlation. Results: Serum and saliva levels of TNF‐α, APRIL, BAFF, IL‐6, and IL‐10 were similar in CP and AgP groups. Serum levels of TNF‐α, APRIL, and BAFF and saliva levels of BAFF were significantly higher in periodontitis groups than healthy controls (P <0.05). Non‐smokers with CP or AgP had lower levels of saliva TNF‐α and APRIL and serum APRIL and IL‐6 than smokers with CP or AgP (P <0.05). Saliva APRIL and serum TNF‐α and IL‐6 levels were significantly higher in healthy smokers than healthy non‐smokers (P <0.05). Clinical periodontal parameters correlated positively with TNF‐family cytokines and negatively with IL‐10 (P <0.05). Conclusions: Within the limits of this study, it may be suggested that elevated salivary and serum TNF‐α, APRIL, and BAFF in patients with periodontitis may contribute to the dominance of B cells in periodontitis lesions. Moreover, higher levels in healthy smokers than non‐smoking counterparts may play a role in detrimental effects of smoking on periodontal tissues.     

Serum placental growth factor, vascular endothelial growth factor, soluble vascular endothelial growth factor receptor-1 and -2 levels in periodontal disease, and adverse pregnancy outcomes

Background: The aim of this study is the evaluation of levels of serum interleukin (IL)‐1β, IL‐6, IL‐10, tumor necrosis factor (TNF)‐α, vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and soluble VEGF receptor (sVEGFR)‐1 and ‐2 in the association between periodontal disease and adverse pregnancy outcomes. Methods: One hundred and nine mothers, who recently gave birth, and 51 women who were not recently pregnant, aged 18 to 35 years, were included in this study. The mothers were classified as term birth, preterm birth (PTB), and preterm low birth weight (PLBW) in respect to their gestational age and baby's birth weight. The birth mothers were grouped as having gingivitis or periodontitis. The non‐pregnant group also included periodontally healthy patients. Venous blood samples were collected to evaluate serum IL‐1β, IL‐6, IL‐10, TNF‐α, VEGF, PIGF, and sVEGFR‐1 and ‐2 levels. Results: Mother's weight, education, and income level were significantly associated with pregnancy outcomes. Serum levels of IL‐1β, TNF‐α, IL‐6, VEGF, and sVEGFR‐1 and ‐2 showed an increase in significance when related to pregnancy. Whereas in the PLBW group IL‐1β, VEGF, and sVEGFR‐2 levels were increased, in the PTB group sVEGFR‐1 levels were increased. Additionally, the patients in the PLBW group with periodontitis had higher serum levels of IL‐1β, VEGF, sVEGFR‐2, and IL‐1β/IL‐10. Conclusion: The serum levels of IL‐1β, VEGF, and sVEGFR‐1 and ‐2 may have a potential effect on the mechanism of the association between periodontal disease and adverse pregnancy outcomes.     

Effect of Intensive Oral Hygiene Regimen During Pregnancy on Periodontal Health,Cytokine Levels,and Pregnancy Outcomes: A Pilot Study

Background: Data are limited on the potential effect of intensive oral hygiene regimens and periodontal therapy during pregnancy on periodontal health, gingival crevicular fluid (GCF) and serum cytokines, and pregnancy outcomes. Methods: A clinical trial was conducted on 120 community‐dwelling, 16‐ to 35‐year‐old pregnant women at 16 to 24 weeks of gestation. Each participant presented with clinical evidence of generalized, moderate‐to‐severe gingivitis. Oral hygiene products were provided, together with instructions for an intensive daily regimen of hygiene practices. Non‐surgical therapy was provided at baseline. Oral examinations were completed at baseline and again at 4 and 8 weeks. In addition, samples of blood and GCF were collected at baseline and week 8. Mean changes in clinical variables and GCF and serum cytokine levels (interleukin [IL]‐1β, IL‐6, tumor necrosis factor [TNF]‐α) between baseline and week 8 were calculated using paired t test. Pregnancy outcomes were recorded at parturition. Results: Results indicated a statistically significant reduction in all clinical variables (P <0.0001) and decreased levels of TNF‐α (P = 0.0076) and IL‐1β (P = 0.0098) in GCF during the study period. The rate of preterm births (<37 weeks of gestation) was 6.7% (P = 0.113) and low birth weight (<2,500 g) was 10.2% (P = 1.00). Conclusions: Among the population studied, intensive instructions and non‐surgical periodontal therapy provided during 8 weeks at early pregnancy resulted in decreased gingival inflammation and a generalized improvement in periodontal health. Large‐scale, randomized, controlled studies are needed to substantiate these findings.     

Periodontitis-associated up-regulation of systemic inflammatory mediator level may increase the risk of coronary heart disease

Nakajima T, Honda T, Domon H, Okui T, Kajita K, Ito H, Takahashi N, Maekawa T, Tabeta K, Yamazaki K. Periodontitis‐associated up‐regulation of systemic inflammatory mediator level may increase the risk of coronary heart disease. J Periodont Res 2009; doi: 10.1111/j.1600‐0765.2009.01209.x. © 2009 John Wiley & Sons A/S Background and Objective: Although an elevation in the concentration of high‐sensitivity C‐reactive protein (hs‐CRP) as a result of periodontal infection may account for an increased risk of developing coronary heart disease (CHD), the effect of periodontal infection on the level of hs‐CRP in an otherwise healthy Japanese population has not yet been reported. The aim of the present study was to confirm, on a larger scale, our previous pilot study findings that both chronic periodontitis and subsequent periodontal treatment alter the serum levels of C‐reactive protein (CRP), interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α). Material and Methods: The concentrations of serum hs‐CRP, IL‐6 and TNF‐α were measured in 78 periodontitis patients at baseline and at re‐assessment, and in 40 periodontally healthy subjects at the time of examination. Results: The concentrations of hs‐CRP and IL‐6 in the sera of periodontitis patients were significantly higher than those in control subjects. By contrast, the concentration of TNF‐α was significantly lower in periodontitis patients than in control subjects. Whereas periodontal treatment decreased the levels of serum hs‐CRP and IL‐6, no such effect was observed for TNF‐α. When the patients were subdivided into four groups according to their initial concentration of hs‐CRP, only the CRP and IL‐6 concentrations of the highest quartile group showed a significant reduction following periodontal treatment. No significant difference in the initial clinical parameters was observed in any quartile. Conclusion: Although periodontal infection does affect the concentration of hs‐CRP and IL‐6 in serum, a subgroup of patients exist who are highly susceptible to an increased risk of CHD associated with periodontitis, suggesting that there may be subjects who have an elevated risk of CHD independent of susceptibility to periodontal tissue destruction per se.     

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.     

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.     

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.     

Group of serum inflammatory markers and periodontitis-metabolic syndrome coexistence in Koreans

Background: Recent epidemiologic studies have shown that individuals with periodontitis have a significantly increased risk of metabolic syndrome (MetS). Chronic infection and subsequent production of systemic inflammatory markers may be associated with this increased risk. The aim of present study is to determine whether the presence of periodontitis and MetS is associated with a group or an individual of C‐reactive protein (CRP), interleukin (IL)‐1β, IL‐6, IL‐8, tumor necrosis factor‐α (TNF‐α), and homocysteine (HCY) in the serum of a Korean population. Methods: Medical and periodontal parameters, including CRP, IL‐1β, IL‐6, IL‐8, TNF‐α, and HCY, were evaluated in 118 individuals (73 healthy; 20 with periodontitis only; 13 with MetS only; and 12 with both). The community periodontal index was used to assess periodontitis. Age, sex, monthly household income, smoking, and drinking were evaluated as confounders. Analysis of covariance, linear regression analysis, and factor analysis were applied. Results: The group of serologic cytokines was synergistically associated with the periodontitis–MetS coexistence. TNF‐α and IL‐6 were two representing serologic cytokines in the group. Conclusions: Our results suggest that a group of systemic biologic markers represented by TNF‐α and IL‐6 might mediate the association between MetS and periodontitis adjusted for various confounders. Additional evidence is needed to generalize our results more widely.     

Osteocalcin, prostaglandin E2 and alkaline phosphatase in gingival crevicular fluid: their relations to periodontal status

Abstract. Prostaglandin E₂ (PGE₂) and alkaline phosphatase (ALP) have often been measured in gingival crevicular fluid (GCF) as possible indicators of gingival inflammation and bone metabolism. Osteocalcin (OC), a major component of bone matrix, is mainly produced by osteoblasts, and could also be considered as a marker of bone turnover. The aims of this preliminary study were lo examine if OC was present in GCF and to assess the relationships of OC, PGE₂, and ALP in GCF to periodontal conditions. GCF samples were collected with durapore strips from 34 healthy, 12 gingivitis and 118 periodontitis sites in 17 subjects. ELISA techniques were used for the determinations of OC and PGE₂. ALP was measured spectrophotometrically by using p-nitrophenyl phosphate as substrate. Total amounts and concentrations of PGE₂ and ALP were significantly higher in periodontitis as compared to healthy and gingivitis sites, and were significantly and positively correlated with probing depth (PD) and gingival index (GI). OC was present in GCF from both healthy and diseased sites with mean concentrations more than ten times greater than normal serum levels. Total OC amounts from strips soaked with GCF from periodontitis sites were significantly higher than those Found in healthy and gingivitis sites. When the data were expressed as concentrations, OC showed significantly positive correlations with GI, but not with PD. However, total amounts of OC significantly correlated with both clinical parameters. OC, PGE₂ and ALP were found to have significantly positive correlations with each other, both when expressed as total amounts and concentrations. These data suggest that a significant amount of OC present in GCF is produced locally by periodontal tissues. Total OC amounts in GCF, as well as PGE₂, and ALP levels, can be considered as potential markers of periodontitis. However, in order to better define the capacity of such mediators for diagnosis, additional longitudinal studies are needed.     

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.     

Diabetes mellitus-associated periodontitis: differences between type 1 and type 2 diabetes mellitus

Aspriello SD, Zizzi A, Tirabassi G, Buldreghini E, Biscotti T, Faloia E, Stramazzotti D, Boscaro M, Piemontese M. Diabetes mellitus‐associated periodontitis: differences between type 1 and type 2 diabetes mellitus. J Periodont Res 2011; 46: 164–169. © 2010 John Wiley & Sons A/S Background and Objective: Although many studies have appeared about diabetes mellitus‐associated periodontitis, few have compared periodontitis inflammatory markers between type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and information regarding this issue is scarce and contradictory. We evaluated the levels of plasma C‐reactive protein and of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) in gingival crevicular fluid in two groups of subjects affected by T1DM and T2DM, in order to identify possible differences between the two classes in the inflammatory mechanisms of diabetes mellitus‐associated periodontitis. Material and Methods: Plasma C‐reactive protein and gingival crevicular fluidIL‐1β, IL‐6 and TNF‐α were measured in periodontitis patients affected by type 1 (P‐T1DM, n = 24) and type 2 diabetes mellitus (P‐T2DM, n = 24). Results: Gingival crevicular fluid levels of IL‐1β and TNF‐α in P‐T1DM subjects were significantly higher than in P‐T2DM subjects. In P‐T1DM subjects, we found significant negative correlations between the duration of diabetes mellitus and IL‐1β and between the duration of diabetes mellitus and TNF‐α. Conclusion: This study shows that IL‐1β and TNF‐α levels in periodontitis patients with T1DM are affected by the duration of diabetes mellitus.     

MAPKs, activator protein-1 and nuclear factor-κB mediate production of interleukin-1β-stimulated cytokines, prostaglandin E₂ and MMP-1 in human periodontal ligament cells

Murayama R, Kobayashi M, Takeshita A, Yasui T, Yamamoto M. MAPKs, activator protein‐1 and nuclear factor‐κB mediate production of interleukin‐1β‐stimulated cytokines, prostaglandin E ₂ and MMP‐1 in human periodontal ligament cells. J Periodont Res 2011; 46: 568–575. © 2011 John Wiley & Sons A/S Background and Objective: Determination of the interleukin‐1 (IL‐1) signaling cascades that lead to the production of various inflammatory mediators and catabolic factors may clarify attractive targets for therapeutic intervention for periodontitis. We comprehensively assessed the involvement of MAPKs, activator protein‐1 (AP‐1) and nuclear factor‐κB (NF‐κB) in IL‐1β‐induced production of interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), prostaglandin E₂ (PGE₂) and MMP‐1 in human periodontal ligament cells. Material and Methods: Human periodontal ligament cells were pretreated with an inhibitor for each of the MAPKs or NF‐κB and subsequently treated with IL‐1β. Following treatment, phosphorylation of three types of MAPK (ERK, p38 MAPK and c‐Jun N‐terminal kinase), IκB kinase (IKK) α/β/γ and IκB‐α, as well as the DNA binding activity of AP‐1 and NF‐κB and the production of IL‐6, IL‐8, PGE₂ and MMP‐1, were determined by western blotting, a gel mobility shift assay and ELISA, respectively. Results: The three MAPKs, simultaneously activated by IL‐1β, mediated the subsequent DNA binding of AP‐1 at various magnitudes, while IKKα/β/γ, IκB‐α and NF‐κB were also involved in the IL‐1 signaling cascade. Furthermore, IL‐1β stimulated the production of IL‐6, IL‐8, PGE₂ and MMP‐1 via activation of the three MAPKs and NF‐κB, because inhibitors of these significantly suppressed the IL‐1β‐stimulated production of these factors. Conclusion: Our results strongly suggest that MAPK, AP‐1 and NF‐κB mediate the IL‐1β‐stimulated synthesis of IL‐6, IL‐8, PGE₂ and MMP‐1 in human periodontal ligament cells. Therefore, inhibition of activation of MAPK, AP‐1 and/or NF‐κB may lead to therapeutic effects on progression of periodontitis.     

Alcohol Consumption and Periodontitis: Quantification of Periodontal Pathogens and Cytokines

Background: There are few studies on periodontal status related to microbiologic and immunologic profiles among individuals not or occasionally using alcohol and those with alcohol dependence. The aim of this study is to determine the effect of alcohol consumption on the levels of subgingival periodontal pathogens and proinflammatory cytokines (interleukin [IL]‐1β and tumor necrosis factor [TNF]‐α) in the gingival fluid among individuals with and without periodontitis. Methods: This observational analytic study includes 88 volunteers allocated in four groups (n = 22): individuals with alcohol dependence and periodontitis (ADP), individuals with alcohol dependence and without periodontitis (ADNP), individuals not or occasionally using alcohol with periodontitis (NAP), and individuals not or occasionally using alcohol without periodontitis (NANP). Levels of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Eikenella corrodens, and Fusobacterium nucleatum were determined by real‐time polymerase chain reaction on the basis of the subgingival biofilm, and IL‐1β and TNF‐α were quantified by enzyme‐linked immunosorbent assay in gingival fluid samples. Results: Individuals with alcohol dependence showed worse periodontal status and higher levels of P. intermedia, E. corrodens, F. nucleatum, and IL‐1β than non‐users. No significant correlations between TNF‐α and bacterial levels were observed. However, in the ADP group, higher levels of E. corrodens were correlated with higher levels of IL‐1β. Conclusion: A negative influence of alcohol consumption was observed on clinical and microbiologic periodontal parameters, as well as a slight influence on immunologic parameters, signaling the need for additional studies.