Cytokine expression in peri-implant crevicular fluid in relation to bacterial presence.

AIM: The aim was to assess clinical inflammatory parameters, cytokine levels and bacterial counts in samples from implant crevicular fluid in cases with untreated peri-implantitis. MATERIAL AND METHODS: Several bacterial species known to up-regulate pro-inflammatory cytokines have been associated with peri-implantitis. The Luminex magnet bead technology was used to study cytokines in crevicular fluid. The checkerboard DNA-DNA hybridization method was used to study bacterial counts in samples from 41 implants (41 individuals). RESULTS: Profuse bleeding and suppuration was found in 25/41 (61.0%) of the implants. The reliability of duplicate cytokine processing was high. In the presence of profuse bleeding, higher pg/ml levels of IL-1ß (p = 0.02), IL-8 (p = 0.04), TNF-α (p = 0.03) and VEGF (p = 0.004) were found. Higher concentrations of IL-1ß were found in the presence of suppuration, and if Escherichia coli (p = 0.001) or Staphylococcus epidermidis (p = 0.05) could be detected. CONCLUSION: Profuse bleeding and/or suppuration in untreated peri-implantitis can be associated with higher concentrations of IL-1ß, IL-8, TNF-α and VEGF in peri-implant crevicular fluid. A higher concentration of IL-1ß in peri-implant crevicular fluid was found in samples that were positive for E. coli or S. epidermidis.

Tumor necrosis factor-α and oral inflammation in patients with Crohn disease.

BACKGROUND: Crohn disease (CD) is a chronic inflammatory bowel disease often accompanied by periodontal symptoms. Based on its function in immune response, tumor necrosis factor (TNF)-α and its genetic variants have been discussed as risk indicators in inflammatory processes. Therefore, the aim of the present study is to investigate the impact of TNF-α polymorphisms on periodontal parameters and inflammatory lesions of oral mucosa as a characteristic of CD. METHODS: A total of 142 patients with CD were included in the study. Oral soft tissue alterations and periodontal parameters were assessed. Genotypes, alleles, and haplotypes of TNF-α polymorphisms (rs1800629, cDNA-308G > A; and rs361525, cDNA-238G > A) were determined by polymerase chain reaction with sequence-specific primers (PCR-SSP). RESULTS: Patients with CD who exhibit more severe oral soft tissue alterations were significantly more often A allele carriers of rs361525 than G allele carriers (14.2% versus 2.2%; P <0.001). Furthermore, A allele carriers had a higher mean periodontal probing depth (P <0.05), mean clinical attachment level (P <0.05), and sites with bleeding on probing (not significant). Similar results were obtained when evaluating A allele-containing genotypes (AG + AA) and haplotypes (GA). In multivariate analyses considering age, sex, smoking, and medication as confounders, the A allele was proven to be an independent risk indicator for oral soft tissue alterations in patients with CD. No genotype-dependent influence of rs1800629 was observed. CONCLUSION: The TNF-α A allele of rs361525 represents a significant risk indicator for oral soft tissue alterations in patients with CD.

Effect of the menstrual cycle on inflammatory cytokines in the periodontium.

BACKGROUND AND OBJECTIVE: The effects of different levels of steroid hormones, as experienced during puberty, pregnancy and menopause, on the periodontium have been demonstrated, but changes in sex hormone levels during the menstrual cycle, and the influence of these changes on the periodontium, remain unresolved. The aim of this study was to investigate the effect of the menstrual cycle on the levels of interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid and on periodontal clinical parameters, including the gingival bleeding index (GBI) and the modified gingival index (MGI), in periodontally healthy women. MATERIAL AND METHODS: Twenty-seven periodontally healthy women with a regular menstrual cycle were included in the study. Clinical parameters, including the GBI, the MGI and the simplified oral health index, were recorded during menstruation, ovulation and premenstruation phases (e.g. on days 1-2, 12-14 and 22-24, respectively) of the menstrual cycle. Gingival crevicular fluid and unstimulated saliva were collected, at each study phase, for assessment of IL-1ß, TNF-α, estrogen and progesterone. RESULTS: Both the GBI and the MGI increased significantly during the menstrual cycle, and were significantly higher during ovulation than during menstruation or premenstruation (p < 0.001). No significant change in the simplified oral health index was observed during the menstrual cycle ( p = 0.18). The levels of IL-1ß and TNF-α increased during the different phases of the menstrual cycle, but only the change in the TNF-α concentration was significant ( p < 0.05). CONCLUSION: This study indicated that changes occurring during the menstrual cycle influence the periodontium and induce inflammatory conditions.

Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti-citrullinated peptide antibody titres.

BACKGROUND: Anti-citrullinated protein antibody (ACPA) responses may precede clinical onset of rheumatoid arthritis. Porphyromonas gingivalis peptidylarginine deiminase can citrullinate proteins possibly inducing autoimmunity in susceptible individuals. AIM: To determine whether periodontitis, carriage of P. gingivalis, smoking and periodontal therapy influence ACPA titres. METHODS: Serum and plaque samples were collected from 39 periodontitis patients before and after non-surgical periodontal treatment, and from 36 healthy subjects. Carriage of P. gingivalis was determined by PCR of plaque DNA. ACPA was determined by anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assay (ELISA). Anti-P. gingivalis titres were determined by ELISA. RESULTS: Untreated periodontitis patients had higher anti-CCP antibody titres than healthy controls [three patients (8%) greater than manufacturer suggested assay diagnostic threshold (5 Assay Units/AU) versus none (0%); mean ± SEM: 1.37 ± 0.23 versus 0.40 ± 0.10 AU, p < 0.0001]. Periodontitis patients who smoked demonstrated lower anti-P. gingivalis (15956 ± 4385 versus 2512 ± 1290 Units/ml, p < 0.05), but similar anti-CCP than non-smoking periodontitis patients (smokers: 1.31 ± 0.35; non-smokers: 1.41 ± 0.32 AU). Healthy smokers demonstrated elevated anti-CCP titres (0.75 ± 0.19 AU), at levels between healthy non-smokers (0.15 ± 0.05 AU) and non-smoker periodontitis patients. Six months after periodontal treatment, there were significant reductions in anti-CCP (non-smokers p < 0.05) and anti-P. gingivalis (all participants p < 0.01). CONCLUSION: In subjects with periodontitis, P. gingivalis infection may be responsible for inducing autoimmune responses that characterize rheumatoid arthritis.

Differential expression of mitogen activating protein kinases in periodontitis.

AIM: Following toll-like receptor (TLR) engagement, lipopolysaccharide (LPS) can stimulate the expression of pro-inflammatory cytokines thus activating the innate immune response. The production of inflammatory cytokines results, in part, from the activation of kinase-induced signalling cascades and transcriptional factors. Of the four distinct classes of mitogen-activated protein kinases (MAPK) described in mammals, p38, c-Jun N-terminal activated kinases (JNK1-3) and extracellular activated kinases (ERK1,2) are the best studied. Previous data have established that p38 MAPK signalling is required for inflammation and bone loss in periodontal disease pre-clinical animal models. MATERIALS & METHODS: In this study, we obtained healthy and diseased periodontal tissues along with clinical parameters and microbiological parameters. Excised fixed tissues were immunostained with total and phospho-specific antibodies against p38, JNK and ERK kinases. RESULTS: Intensity scoring from immunostained tissues was correlated with clinical periodontal parameters. Rank correlations with clinical indices were statistically significantly positive (p-value < 0.05) for total p38 (correlations ranging 0.49-0.68), phospho-p38 (range 0.44-0.56), and total ERK (range 0.52-0.59) levels, and correlations with JNK levels also supported association (range 0.42-0.59). Phospho-JNK and phospho-ERK showed no significant positive correlation with clinical parameters of disease. CONCLUSION: These data strongly implicate p38 MAPK as a major MAPK involved in human periodontal inflammation and severity.

Innate immune receptor expression in peri-implant tissues of patients with different susceptibility to periodontal diseases.

BACKGROUND: Although inflammation mediates the pathogenesis of periodontal diseases, the effects of innate immune responses on implant therapies have not been evaluated. Innate immune receptors, including toll-like-receptors (TLRs) and the receptor for advanced glycated end-products (RAGE), are upregulated within inflamed gingiva and are responsible for initiation of detrimental host responses. The aim of this study is to compare the expression of TLR2, TLR4, and RAGE in gingival tissues from participants susceptible to periodontitis and participants not susceptible to periodontitis before and after implant therapy. METHODS: Periodontally healthy participants received implant therapy for non-periodontal edentulism. Participants susceptible to periodontitis were diagnosed with chronic periodontitis prior to implant therapy. Gingival biopsies were collected from edentulous ridges before implant installation and from peri-implant mucosa 2 months after treatment. Histology, real-time PCR, and Western blot were used to evaluate levels of inflammatory infiltrate, TLR2, TLR4, and RAGE expression. RESULTS: Before implant therapy, elevated levels of RAGE were detected in gingival tissues from participants susceptible to periodontitis when compared to those from participants with healthy periodontiums, whereas no differences in the expression of TLR2 or TLR4 were detected. After implant therapy, there was an upregulation of RAGE and TLR4 levels that coincided with a downregulation of TLR2 levels in biopsies from participants susceptible to periodontitis. Levels of RAGE and TLR4 remained unchanged in biopsies from participants with healthy periodontiums, whereas TLR2 levels were significantly upregulated. Histologically, post-implant biopsies from participants susceptible to periodontitis displayed higher levels of inflammatory infiltrate. CONCLUSION: Elevated levels of inflammatory potential were found after implant therapy in participants susceptible to periodontitis.

Gingival fluid cytokine expression and subgingival bacterial counts during pregnancy and postpartum: a case series.

OBJECTIVES: The aim of this study was to assess gingival fluid (GCF) cytokine messenger RNA (mRNA) levels, subgingival bacteria, and clinical periodontal conditions during a normal pregnancy to postpartum. MATERIALS AND METHODS: Subgingival bacterial samples were analyzed with the checkerboard DNA-DNA hybridization method. GCF samples were assessed with real-time PCR including five proinflammatory cytokines and secretory leukocyte protease inhibitor. RESULTS: Nineteen pregnant women with a mean age of 32 years (S.D. ± 4 years, range 26-42) participated in the study. Full-mouth bleeding scores (BOP) decreased from an average of 41.2% (S.D. ± 18.6%) at the 12th week of pregnancy to 26.6% (S.D. ± 14.4%) at the 4-6 weeks postpartum (p < 0.001). Between week 12 and 4-6 weeks postpartum, the mean probing pocket depth changed from 2.4 mm (S.D. ± 0.4) to 2.3 mm (S.D. ± 0.3) (p = 0.34). Higher counts of Eubacterium saburreum, Parvimonas micra, Selenomonas noxia, and Staphylococcus aureus were found at week 12 of pregnancy than at the 4-6 weeks postpartum examinations (p < 0.001). During and after pregnancy, statistically significant correlations between BOP scores and bacterial counts were observed. BOP scores and GCF levels of selected cytokines were not related to each other and no differences in GCF levels of the cytokines were observed between samples from the 12th week of pregnancy to 4-6 weeks postpartum. Decreasing postpartum counts of Porphyromonas endodontalis and Pseudomonas aeruginosa were associated with decreasing levels of Il-8 and Il-1ß. CONCLUSIONS: BOP decreased after pregnancy without any active periodontal therapy. Associations between bacterial counts and cytokine levels varied greatly in pregnant women with gingivitis and a normal pregnancy outcome. Postpartum associations between GCF cytokines and bacterial counts were more consistent. CLINICAL RELEVANCE: Combined assessments of gingival fluid cytokines and subgingival bacteria may provide important information on host response.

Periodontal condition of patients with autoimmune diseases and the effect of anti-tumor necrosis factor-α therapy.

BACKGROUND: The aim of this study is to evaluate the effect of autoimmune diseases (AIs), as well as anti-tumor necrosis factor-α (TNF-α) therapy on the clinical and immunologic parameters of the periodontium. METHODS: Thirty-six AI patients (12 rheumatoid arthritis [RA], 12 psoriatic arthritis, and 12 systemic sclerosis) were recruited together with 12 healthy (H) and 10 RA patients receiving anti-TNF-α therapy (RA+). Periodontal indices including plaque index, gingival index (GI), probing depth (PD), and bleeding on probing (BOP) were measured, and gingival crevicular fluid (GCF) was collected from five deepest pockets using papers strips. The TNF-α level was analyzed using enzyme-linked immunosorbent assay. Analysis of variance test was used for statistical comparison between groups, whereas Pearson linear correlation coefficient test was used to examine the association between TNF-α and periodontal status indices. RESULTS: The three AI subgroups were very similar in clinical and immunologic parameters. GI was greater in the AI patients compared to the H and RA+ groups (1.91 ± 0.54, 1.21 ± 0.67, and 1.45 ± 0.30, respectively, P = 0.0005). AI patients exhibited significantly more BOP than H and RA+ (46.45% ± 17.08%, 30.08% ± 16.86%, and 21.13% ± 9.51%, respectively, P = 0.0002). PD in H and RA+ groups were lower than in the AI (3.47 ± 0.33, 3.22 ± 0.41, and 3.91 ± 0.49 mm, P = 0.0001). Number of sites with PD >4 mm was higher in AI patients compared to H and RA+ (42.44 ± 17.5 versus 24.33 ± 15.62 versus 33.3 ± 6.6, P = 0.0002). GCF TNF-α was higher among the AI patients (1.67 ± 0.58 ng/site) compared to 1.07 ± 0.33 ng/site for the H group and 0.97 ± 0.52 ng/site for the RA+ group (P = 0.0002). A significant positive correlation was found between PD and TNF-α levels in the GCF (r = 0.4672, P = 0.0002), BOP (r = 0.7491, P = 0.0001), and GI (r = 0.5420, P = 0.0001). CONCLUSIONS: Patients with AI diseases have higher periodontal indices and higher TNF-α levels in GCF than H controls. Anti-TNF-α treatment appears to reverse this phenomenon.

Comparison of CCL28, interleukin-8, interleukin-1ß and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis.

BACKGROUND AND OBJECTIVE: Cytokines produced by various cells are strong local mediators of inflammation. Mucosa-associated epithelial chemokine (CCL28), interleukin-8 (IL-8), interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) are major cytokines that play important roles in the periodontal inflammatory process. In this study we aimed to compare the levels of CCL28, IL-8, IL-1ß and TNF-α in the gingival crevicular fluid of both periodontally healthy subjects and in subjects diagnosed with gingivitis, chronic periodontitis and generalized aggressive periodontitis. MATERIAL AND METHODS: A total of 84 subjects participated in the study: 21 subjects had gingivitis, 21 subjects had chronic periodontitis, 21 subjects had generalized aggressive periodontitis and 21 were periodontally healthy. The levels of CCL28, IL-8, IL-1ß and TNF-α were analyzed using enzyme-linked immune sorbent assay (ELISA). RESULTS: The total levels of CCL28 and IL-8 in the gingival crevicular fluid of the generalized aggressive periodontitis group (324.74 ± 42.62 pg/30 s, 487.62 ± 49.21 pg/30 s) were significantly higher than those of the chronic periodontitis group (268.81 ± 28.64 pg/30 s, 423.65 ± 35.24 pg/30 s), the gingivitis group (146.35 ± 17.46 pg/30 s, 310.24 ± 48.20 pg/30 s) and the periodontally healthy group (92.46 ± 22.04 pg/30 s, 148.41 ± 24.64 pg/30 s). Similarly, the total levels of IL-1ß and TNF-α in the generalized aggressive periodontitis group (110.23 ± 9.20 pg/30 s, 1284.46 ± 86.32 pg/30 s) were significantly higher than those in the chronic periodontitis group (423.65 ± 35.24 pg/30 s, 82.64 ± 9.12 pg/30 s), the gingivitis group (52.10 ± 7.15 pg/30 s, 824.24 ± 44.68 pg/30 s) and the periodontally healthy group (36.44 ± 8.86 pg/30 s, 628.26 ± 34.61 pg/30 s). CONCLUSION: CCL28, IL-8, IL-1ß and TNF-α may play key roles in the host response to inflammation in periodontal diseases. As the severity of periodontal diseases increases, destruction of periodontal tissues also increases. Inflammation is one among many factors that trigger periodontal tissue destruction. Identification of the mediators that influence the development and progression of inflammation in periodontal diseases may be very important in understanding the prognoses of periodontal diseases.

Expression of peptidylarginine deiminase-2 and -4, citrullinated proteins and anti-citrullinated protein antibodies in human gingiva.

BACKGROUND AND OBJECTIVE: The presence of citrullinated proteins, and peptidylarginine deiminase types -2 (PAD-2) and -4 (PAD-4) in periodontal tissues, determine the presence of anti-cyclic citrullinated protein antibodies (anti-CCP) in gingival crevicular fluid (GCF) and compare the expression of these proteins between inflamed and non-inflamed sites. MATERIAL AND METHODS: Tissue sections were stained using antibodies against citrullinated proteins, PAD-2 and PAD-4. RT-PCR was performed to investigate PAD-2 and PAD-4 mRNA in inflamed and non-inflamed gingival tissues. Anti-CCP antibodies in gingival crevicular fluid were detected by ELISA. RESULTS: Citrullinated proteins, PAD-2 and PAD-4 were detected in gingiva. There was a correlation between inflammation and expression of these proteins. mRNAs for PAD-2 and PAD-4 were detected in both inflamed and non-inflamed gingival tissues. Antibodies to CCP were found mostly in the GCF of individuals with periodontitis. CONCLUSION: PAD-2 and PAD-4 (protein and mRNA) as well as citrullinated proteins are present in inflamed gingiva, and anti-CCP antibodies can be detected in the GCF of some patients. Tissue expression of citrullinated proteins and PAD increased with the severity of inflammation. The presence of anti-CCP antibodies in GCF was almost exclusive to a subset of patients with periodontitis. Increased expression of these proteins in inflamed gingiva lends support to the notion that periodontal inflammation contributes to the inflammatory burden in a similar way to rheumatoid arthritis.

The importance of genetic variants in TNFα for periodontal disease in a cohort of coronary patients.

AIM: The aim of this analysis was to evaluate the importance of genetic variants of TNFα for the severity of periodontal disease and periodontal risk factors with respect to periodontal risk factors in a cohort of coronary patients. SUBJECTS: A total of 942 consecutive patients with angiographic proven coronary heart disease were prospectively included in the study entitled "Periodontitis and Its Microbiological Agents as Prognostic Factors in Patients With Coronary Heart Disease" (ClinicalTrials.gov identifier:NCT01045070). METHODS: After including of patients, an extensive periodontal examination also involving PCR-sampling for 11 periodontal bacteria was performed. In this subanalysis, single nucleotide polymorphisms (SNPs) c.-308G>A, c.-238G>A and haplotypes for TNFα were analysed by CTS-PCR-SSP Tray kit (Heidelberg, Germany). RESULTS: The AG+AA genotype of SNP c.-238G>A of TNFα gene was associated with the amount of clinical attachment loss in patients with coronary heart disease in multivariate regression analysis. Moreover, Prevotella intermedia occurred more frequently in carriers who were positive for the AG+AA genotype and A-allele of SNP c.-308G>A in bivariate and multivariate analyses. Furthermore, only in bivariate analyses significant associations of genetic variants of TNFα with intensified bleeding on probing and with higher plasma level of interleukin 6 could be shown. CONCLUSIONS: Genetic variants of TNFα gene, namely c.-308G>A and c.-238G>A, are associated with periodontal conditions in patients with coronary heart disease.

Proinflammatory cytokine levels in hyperlipidemic patients with periodontitis after periodontal treatment.

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.

Expression of the interleukin-10 signaling pathway genes in individuals with Down syndrome and periodontitis.

BACKGROUND: Individuals with Down syndrome (DS) have a higher prevalence and severity of periodontal disease, which cannot be explained by poor oral hygiene alone and is related to changes in the immune response. The aim of this study is to evaluate whether DS was associated with differential modulation of expression of genes associated with proinflammatory and anti-inflammatory responses in periodontal disease. METHODS: A total of 51 individuals were evaluated: 19 individuals with DS and periodontal disease (group 1), 20 euploid individuals with periodontal disease (group 2; positive control), and 12 euploid individuals without periodontal disease (group 3; negative control). Clinical periodontal evaluation and gingival biopsies were performed. Quantitative reverse transcription-polymerase chain reaction was used to determine expression levels of interleukin-10 (IL-10), the receptors IL-10RA and IL-10RB, intracellular adhesion molecule 1 (ICAM-1), interferon-γ-inducible protein 10 (IP-10), and the signaling intermediates Janus kinase 1, signal transducer and activator of transcription 3 (STAT-3), and suppressor of cytokine signaling 3 (SOCS-3). RESULTS: Expression of IL10, SOCS3, IP10, and ICAM1 mRNA in DS patients was significantly lower compared to euploid individuals with periodontal disease, whereas IL-10RB and STAT-3 mRNA levels were higher in individuals with DS. CONCLUSION: Reduced expression of IL-10 coupled with a possible increase of STAT3 activation (increase of STAT3 and reduction of SOCS3 mRNA) indicates an important modulation of the immune response, with attenuation of anti-inflammatory and increase of proinflammatory mediators. This modulation may be related to the increased prevalence and severity of periodontitis in individuals with DS.

Correlation between periodontal disease, inflammatory alterations and pre-eclampsia.

BACKGROUND AND OBJECTIVE: Several studies have hypothesized that periodontal disease may increase the risk of pre-eclampsia. The correlation between the two diseases would probably be based on hypertension-related cytokine release in the local periodontal environment. The aim of this study was to evaluate the association between periodontal disease and pre-eclampsia, and the correlation of the two conditions with interleukin-6 (IL-6) and tumor necrosis factor-α(TNFα) mRNA expression. MATERIAL AND METHODS: A case-control analysis of 116 pregnant women, 58 with pre-eclampsia (cases) and 58 normotensive pregnant women (controls) was performed. In addition to collection of socio-demographic data and periodontal evaluation, peripheral blood samples were collected for laboratory analysis of IL-6 and TNFα mRNA expression by real-time PCR. RESULTS: There was an association between periodontitis and pre-eclampsia (adjusted odds ratio 3.73; 95% confidence interval 1.32-10.58). Increased TNFα mRNA expression was observed in pre-eclamptic women; however, there was no correlation between periodontitis and systemic cytokine expression. In the case group, systemic cytokine mRNA levels were similar in pregnant women with and without periodontitis (means±SD): 0.73±0.24 vs. 0.82±0.38 for TNFα and 1.31±1.49 vs. 1.09±0.74 for IL-6, respectively. CONCLUSION: Periodontitis was clinically related to pre-eclampsia; however, the supposed mechanism that correlates the two diseases, i.e. a systemic inflammatory process involving cytokines TNFα and IL-6 in the presence of periodontal disease, could not be confirmed in this study.

Expression of IL-6, IL-10, IL-17 and IL-8 in the peri-implant crevicular fluid of patients with peri-implantitis.

OBJECTIVES: The aim of this study was to compare the levels of cytokines IL-6, IL-10 and IL-17 and the chemokine IL-8 in the peri-implant crevicular fluid (PCF) between the group of patients with peri-implantitis (PP) and peri-implantar healthy patients (HP). DESIGN: The PCF was collected from 40 implants regarding 25 patients, being 14 patients with PP and 11 HP totalizing 20 implants from each group. The PCF samples collected from each patient were quantified for IL-6, IL-17, IL-8 and IL-10 using the enzymatic immunosorbent assay (ELISA). RESULTS: The expression of IL-17 was significantly higher in the PP group when compared to HP (p < 0.05). There was no significant difference when comparing the levels of IL-6, IL-8 and IL-10 between both groups HP and PP. Also, there was a significant positive correlation between levels of IL-6 and IL-8 in the PP group. CONCLUSIONS: This study demonstrates that in patients with peri-implantitis there is an increase of IL-17 which may induce the production of other inflammatory cytokines, contributing to the pathogenesis of bone loss in peri-implantitis.

IL-12 and IL-18 levels in serum and gingival tissue in aggressive and chronic periodontitis.

OBJECTIVE: The aim of this study was to compare the levels of interleukin-12 (IL-12) and IL-18 in gingival tissue and serum between patients with chronic (n = 18) or aggressive periodontitis (n = 12) and healthy subjects (HS) (n = 9). METHODS: Gingival tissue biopsies and serum were obtained from all study subjects. The tissue was homogenized and cytokines IL-12 and IL-18 were quantified by enzyme-linked immunosorbent assay. RESULTS: Interleukin-12 levels in gingival tissue were significantly higher in aggressive periodontitis patients than in HS; serum IL-12 was significantly elevated in aggressive periodontitis relative to both chronic periodontitis (CP) and HS. IL-18 levels in gingival tissue showed no significant differences between the groups. Patients with CP showed significantly elevated levels of serum IL-18 compared with HS; however, the aggressive periodontitis group showed no significant differences with either the CP group or the HS. CONCLUSIONS: Our results showed higher levels of IL-12 in gingival tissue and serum of patients with aggressive periodontitis, and IL-18 was elevated in the serum of CP patients. The patterns of IL-12 and IL-18 are different in chronic and aggressive periodontitis; this finding suggests distinctive mechanisms of immunopathogenesis between these forms of periodontitis.

Periodontal disease in association with systemic levels of interleukin-18 and CXC ligand 16 in patients undergoing cardiac catheterization.

BACKGROUND: Interleukin (IL)-18 is a proinflammatory cytokine that is present in chronically inflamed tissues; IL-18 was positively associated with periodontitis and coronary artery disease (CAD). CXC ligand (CXCL) 16, a recently discovered chemokine, was identified in atherosclerotic lesions; its role in periodontal disease is largely unknown. This research study correlates periodontal parameters with systemic levels of IL-18 and CXCL16. METHODS: Fifty-one patients who presented for clinically indicated coronary angiography received full-mouth periodontal examinations. The periodontal status of patients was defined using frequency distributions of probing depth (PD), clinical attachment loss (AL), and bleeding on probing (BOP). Blood samples were collected during cardiac catheterization, and plasma levels of IL-18 and CXCL16 were analyzed. The severity of CAD was determined by the presence and extent of coronary artery stenosis. Correlations between periodontal parameters, levels of inflammatory mediators, and CAD status were analyzed. RESULTS: The extent of BOP exhibited a significant positive correlation with IL-18 in the Spearman rank correlation analysis (P = 0.039), which indicated a correlation between periodontal inflammation and systemic IL-18 levels. When multiple regression analysis was performed, the extent of clinical AL > or =3 mm (P = 0.045) and > or =5 mm (P = 0.024) exhibited an association with IL-18, whereas CXCL16 was associated with clinical AL > or =5 mm (P = 0.040) and PD > or =7 mm (P = 0.047). CONCLUSION: A significant correlation is identified between periodontitis and systemic levels of IL-18 and CXCL16 in patients undergoing diagnostic coronary angiography.

Interleukin-6 (G-174C) and tumour necrosis factor-alpha (G-308A) gene polymorphisms in geriatric patients with chronic periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease, and genetic factors may have an important role in its severity. Polymorphisms in the promoter regions of the interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) genes have been reported to cause changes in the production of these cytokines. The aim of this study was to evaluate the possible role of IL-6 (G-174C) and tumour necrosis factor (G-308A) polymorphisms, in the severity of chronic periodontitis in an elderly population. MATERIALS AND METHODS: In this study, a group of 65 elderly women, comprising 17 patients with moderate chronic periodontitis, 21 with severe chronic periodontitis and 27 healthy patients were selected. DNA was isolated from all subjects, and polymerase chain reaction was used to study the IL-6 and TNF-alpha gene polymorphisms. RESULTS: The results of this study showed a significant difference in the allele and genotype frequencies of IL-6 gene polymorphism between patients with periodontal disease and controls. Subjects carrying the G/G genotype of IL-6 were most severely affected by periodontitis. The TNF-alpha gene polymorphism showed no association with chronic periodontitis between patients and controls. CONCLUSION: The results suggest that the IL-6 gene polymorphism may be associated with chronic periodontitis, and that TNF-alpha gene polymorphism may not be involved in the progression of chronic periodontitis in the population of elderly Brazilian women.

Interleukin-1 gene cluster polymorphisms associated with periodontal disease in type 2 diabetes.

BACKGROUND: Epidemiologic studies have shown an increased frequency, severity, and risk of periodontitis in patients with diabetes. Periodontitis is associated with certain interleukin (IL)-1 gene cluster polymorphisms. Diabetes is a proinflammatory state with increased levels of circulating cytokines suggesting a causal role for inflammation in its etiology. Common genetic factors may be involved in the susceptibility for diabetes and periodontitis. We evaluated the relationships among IL-1 gene polymorphisms, type 2 diabetes, and periodontitis. METHODS: One hundred twelve patients with diabetes and chronic periodontitis, 224 patients without diabetes but with chronic periodontitis, and 208 healthy subjects without periodontitis were studied. All received a clinical periodontal examination and assessment of standard periodontal parameters. IL-1A -889, -1B +3954, and -1B -511 polymorphisms were identified by polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion and gel electrophoresis. Variable numbers of IL-1RN tandem repeats were detected by PCR amplification and fragment-size analysis. RESULTS: The severity and extent of periodontitis was significantly greater in patients with diabetes than in patients without diabetes. No significant differences in IL-1A -899, -1B +3954, or -1RN genotype frequencies were found between patients with diabetes and patients without diabetes. The IL-1A -889 TT genotype (odds ratio [OR] = 2.90; 95% confidence interval [CI] = 1.20 to 7.02), IL-1B +3954 TT genotype (OR = 3.54; 95% CI = 1.15 to 10.85), and IL-1B -511 CC genotype (OR = 2.10; 95% CI = 1.25 to 3.58) were significantly associated with periodontitis. The presence of an IL-1 positive genotype was significantly associated with periodontitis (OR = 1.61; 95% CI = 1.04 to 2.49). No interaction between smoking status and polymorphisms was found. CONCLUSIONS: Periodontitis was significantly associated with some IL-1 gene polymorphisms. No association between diabetes and IL-1A and -1B gene polymorphisms was found.

Periodontal conditions of individuals with Sjögren's syndrome.

BACKGROUND: Sjögren's syndrome (SjS) is a systemic autoimmune disease that might lead to hyposalivation and negatively affect the oral environment. The evidence with regard to the periodontal conditions in this group of subjects is still controversial. This study aimed to evaluate the periodontal clinical conditions and inflammatory markers in gingival crevicular fluid (GCF) from patients with primary Sjögren's syndrome (SjS [P]) or secondary Sjögren's syndrome (SjS [S]) compared to a control group. METHODS: Nineteen individuals with SjS (11 SjS [P] and eight SjS [S]) and 19 controls, matched for gender, age, and tobacco exposure, were selected from two private clinics and a hospital. The groups were compared for stimulated whole saliva (SWS) flow rate, plaque index (PI), gingival index (GI), probing depth (PD), bleeding on probing (BOP), clinical attachment level (CAL), and total amount of interleukin (IL)-1beta and total elastase activity in the GCF. Generalized estimating equations were used for data analysis. RESULTS: Individuals with SjS had a significantly lower SWS flow rate and higher mean PI, GI, PD, CAL, and BOP than controls. After adjustment for plaque, GI remained significantly higher in patients with SjS. Patients with SjS (S) had significantly higher mean CAL and PD than patients with SjS (P), and CAL and BOP remained significantly higher in this subgroup after adjustment. No differences were observed with regard to the GCF inflammatory markers. After adjusting for PD, subjects with SjS (P) showed lower levels of IL-1beta compared to controls. CONCLUSION: SjS seemed to negatively affect the periodontal condition because gingival inflammation was more evident in the individuals with SjS, particularly those with SjS (S).