Ezel Berker

Interleukin-11, interleukin-1β, interleukin-12 and the pathogenesis of inflammatory periodontal diseases

OBJECTIVES The balance between pro-inflammatory and anti-inflammatory cytokines may be crucial for determining the immunopathology of gingivitis (G) and periodontitis. This study aimed to analyse interleukin-1beta (IL-1beta), IL-11 and IL-12 levels in gingival crevicular fluid (GCF) of patients with G and chronic periodontitis (CP). MATERIAL AND METHODS Fourty subjects including 12 CP, 14 G and 14 controls (C) were enrolled. GCF samples were collected from six maxillary sites per patient and analysed for IL-1beta, IL-11 and IL-12 by an enzyme-linked immunosorbent assay. RESULTS Significantly lower concentrations of IL-11 were detected in CP compared with both G and C groups (p<0.05). The CP group had a significantly higher total amount of IL-12 and IL-1beta compared with the C group (p<0.05). The IL-11:IL-1beta cytokine ratio was higher in both G and C groups compared with the CP group. The IL-11:IL-1beta ratio became progressively lower with increasing probing depth (p<0.01). CONCLUSIONS Our data showed that IL-11 levels are significantly decreased in GCF from sites with periodontitis compared with G and healthy sites. Because of the possible preventive effect of IL-11 on inflammation, IL-11 may be an important factor in the therapeutic modulation of periodontal disease.

Effect of inflammation on cytokine levels and bone remodelling markers in peri-implant sulcus fluid: a preliminary report.

OBJECTIVES Since ingredients of peri-implant sulcus fluid (PISF) may be related to the bony structure surrounding dental implants, analyze of specific markers related to bone resorption in PISF seems to be suitable for long term monitoring of peri-implant health. It is suggested that analysis of PISF may serve for detection of inflammation. The aim of this study is to analyze PISF interleukin-1 beta (IL-1β), IL-10, osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL) levels to determine whether the diagnostic value of PISF can be used to evaluate early changes around implants. MATERIALS AND METHODS A total of 47 dental implants either healthy/non-inflamed (n=20) (Group I), or gingivitis/inflamed (n=27) (Group II), were classified. Peri-implant status has been evaluated by clinical evaluation (plaque index, gingival index, probing depth and gingival bleeding time index) were recorded and PISF samples were also obtained. PISF IL-1β, IL-10, RANKL, and OPG levels were measured by enzyme-linked immunosorbent assay. Potential volumetric changes in PISF were also evaluated. RESULTS All clinical parameters and volume of PISF were higher in Group II and these differences were statistically significant except volume values. IL-1β, IL-10 and OPG levels in PISF were significantly higher in Group II. Although the PISF RANKL level in Group II was higher than the level of Group I, the difference between groups did not reach the statistically significant level. CONCLUSIONS These data suggest that a balance of inflammatory- and osteoclastogenesis related molecules locally produced may play an important role in the development of inflammatory peri-implant lesions.

Necessity of Keratinized Tissues for Dental Implants: A Clinical, Immunological, and Radiographic Study

BACKGROUND Necessity of keratinized tissues (KTs) for maintaining health around dental implants (DIs) remains as a controversial issue. PURPOSE The aim of this study was to investigate the effects of KT width (KTW) on peri-implant tissues by evaluating peri-implant clinical and inflammatory parameters. MATERIALS AND METHODS Sixty DIs were included in this 6-month longitudinal study. After classifying DI based on the presence of KTs at the buccal aspect as with adequate/inadequate KTW, DIs were randomly assigned into three study groups. In the first group, while free gingival graft (FGG) was performed, DIs in maintenance (M) group were followed up by standardized maintenance procedures at baseline, first, third, and sixth months as with DI with adequate KTW (Control). Clinical parameters, peri-implant sulcular fluid (PISF) volume, PISF Interleukin 1β concentration, and bone loss were analyzed. RESULTS Significant improvements in clinical and immunological parameters were noted only for FGG for the whole study period. Statistical differences detected between the treatment groups (FGG vs M) were for gingival index at all time points and for PISF volume at sixth month. For the other parameters evaluated, while lower values were observed for FGG, statistically no differences were noted between the groups. CONCLUSIONS Based on the results of this study, it can be suggested that FGG performed around DIs lacking KT is a reliable method, leading to significant improvements in clinical and inflammatory parameters. Further long-term studies including more DIs are needed to clarify the role of KT on maintenance of DIs.

Analysis of TNF-α (-308) polymorphism and gingival crevicular fluid TNF-α levels in aggressive and chronic periodontitis: A preliminary report

OBJECTIVES The purpose of this study was to determine the differences in the distribution of TNF-α (-308) gene polymorphism among aggressive periodontitis, chronic periodontitis and periodontally healthy individuals and also to investigate whether this polymorphism is associated with gingival crevicular fluid TNF-α levels and periodontal disease severity. MATERIAL AND METHODS A total of 93 individuals were enrolled in the study including 38 aggressive periodontitis, 29 chronic periodontitis patients, and 26 healthy controls. Single nucleotide polymorphism at TNF-α (-308) is analyzed by PCR-RFLP method. Gingival crevicular fluid samples were analyzed for TNF-α, using ELISA. RESULTS The distribution of genotypes and allele frequencies for TNF-α (-308) were similar among the groups. After stratification of patients with respect to attachment level, aggressive periodontitis patients with clinical attachment level ⩾4mm was observed to have a higher frequency of TNF-α (-308) allele 2 compared to the chronic periodontitis patients with clinical attachment level ⩾4mm. No significant differences were found between the TNF-α levels of the different genotypes in spite of an insignificant increase in patient groups carrying TNF-α (-308) allele 2. CONCLUSION The results of this study revealed an association between TNF-α (-308) allele 2 frequency and aggressive periodontitis patients with clinical attachment level ⩾4mm in the population studied.

Blocking Proinflammatory Cytokine Release Modulates Peripheral Blood Mononuclear Cell Response to Porphyromonas gingivalis

BACKGROUND Chronic periodontitis (CP) is an inflammatory disease in which cytokines play a major role in the progression of disease. Anti-inflammatory cytokines (interleukin 4 [IL-4] and IL-10) were reported to be absent or reduced in diseased periodontal tissues, suggesting an imbalance between the proinflammatory and anti-inflammatory mediators. This study tests the hypothesis that there is cellular crosstalk mediated by proinflammatory and anti-inflammatory cytokines and that blocking proinflammatory cytokine (tumor necrosis factor-α [TNF-α] and IL-1) production will enhance anti-inflammatory cytokine (IL-4 and IL-10) production from peripheral blood mononuclear cells (PBMCs) in response to Porphyromonas gingivalis. METHODS PBMCs were isolated from individuals diagnosed with CP or healthy individuals and cultured for 24 hours. Concanavalin A (ConA) was used as an activator of lymphocyte function. Live and heat-killed P. gingivalis or lipopolysaccharide from P. gingivalis were used as the bacterial stimulants. TNF-α and IL-1 production was neutralized by specific antibodies against TNF-α and IL-1α or IL-β. Culture supernatants were evaluated by enzyme-linked immunosorbent assay for TNF-α, IL-1β, IL-4, and IL-10 production. RESULTS Live P. gingivalis did not result in any significant IL-10 or IL-4 release, whereas heat-killed P. gingivalis led to a significant increase in IL-10 levels compared with unstimulated or live P. gingivalis-stimulated cells from both healthy individuals or those with CP. Overall, PBMCs from patients with CP produced significantly lower IL-10 in response to ConA and P. gingivalis, suggesting chronic suppression of the anti-inflammatory cytokine production. Blocking the proinflammatory cytokine response did not result in any substantial change in IL-10 or IL-4 response to live P. gingivalis. Blocking the proinflammatory cytokine response restored IL-10 production by cells from CP in response to P. gingivalis lipopolysaccharide. CONCLUSIONS These findings suggest that PBMCs from patients with CP have suppressed anti-inflammatory cytokine production that can, in part, be restored by neutralizing proinflammatory cytokines. Monocytes are an important source of IL-10 production, and monocyte-derived IL-10 might play a regulatory role in the pathogenesis of CP.

Statins and IL-1β, IL-10, and MPO Levels in Gingival Crevicular Fluid: Preliminary Results

Statins possess a wide variety of pleiotropic properties that are independent of their lipid-lowering abilities such as attenuating inflammation, oxidative stress, coagulation, platelet aggregation and stimulating bone formation. The aim of the study is to evaluate the effect of statins on clinical periodontal parameters and gingival crevicular fluid (GCF) levels of IL-1β, IL-10, and myeloperoxidase (MPO) in inflammatory periodontal diseases. Seventy-nine subjects with hyperlipidemia and 48 systemically healthy controls (C) were included. Hyperlipidemic patients were either given a diet (HD) or prescribed statin (HS). Patients were classified into three subgroups as those who were periodontally healthy (h), who had gingivitis (g), or who had chronic periodontitis (p). Blood samples were collected for the measurement of lipid profiles. Plaque index (PI), gingival index (GI), probing pocket depth (PD), clinical attachment level (CAL), and percentage of bleeding on probing (BOP) were recorded. Gingival crevicular fluid levels of IL-1β, IL-10, and MPO were measured in order to determine the anti-inflammatory and antioxidant effects of statins. Probing depth values of the HSp group were significantly lower than those of the Cp group. Percentage of BOP of the HSg group was significantly lower than those of the HDg and Cg groups. While the IL-1β level of the HSp group was significantly lower than that of the HDp group, IL-10 levels of the HSg group were significantly higher than those of the HDg group. MPO levels were significantly lower in the HSg group when compared to those in the HDg and Cg groups. Statin use decreased the IL-1β and MPO levels and enhanced IL-10 in GCF. It can be suggested that statins may attenuate periodontal inflammation and progression of periodontal inflammation.

Increased cancer risk in patients with periodontitis

Abstract Background: Previous studies have noted a possible association between periodontal diseases and the risk of various cancers. We assessed cancer risk in a cohort of patients with moderate to severe periodontitis. Methods: Patients diagnosed with moderate to severe periodontitis by a periodontist between 2001 and 2010 were identified from the hospital registry. Patients younger than 35 years of age or with a prior cancer diagnosis were excluded. The age- and gender-standardized incidence rates (SIR) were calculated by dividing the number of observed cases by the number of expected cases from Turkish National Cancer Registry 2013 data. Results: A total of 280 patients were included (median age 49.6, 54% female). Median follow-up was 12 years. Twenty-five new cancer cases were observed. Patients with periodontitis had 77% increased risk of cancer (SIR 1.77, 95% CI 1.17–2.58, p = .004). Women with periodontitis had significantly higher risk of breast cancer (SIR 2.40, 95% CI 0.88–5.33) and men with periodontitis had significantly higher risk of prostate cancer (SIR 3.75, 95% CI 0.95–10.21) and hematological cancers (SIR 6.97, 95% CI 1.77–18.98). Conclusion: Although showing a causal association necessitates further investigation, our results support the idea that periodontitis might be associated with increased cancer risk, particularly with hematological, breast and prostate cancers.