Periodontal Condition and Immunological Aspects of Individuals Hospitalized in the Intensive Care Unit.

There are few studies on the clinical and immunological periodontal status of intensive care unit (ICU) in-patients. The aim of the present study was to evaluate the periodontal condition among ICU in-patients through clinical and immunological periodontal parameters. From the sample of 373 hospitalized ICU patients, 182 were submitted' to a thorough clinical periodontal and immunological evaluation. Data on bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) were collected and gingival sulcular fluid samples were quantified through ELISA on IL-1, IL-6, and MMP-2 for immunological evaluation. Data was statistically analyzed by Chi-square, Fisher's exact, Mann-Whitney tests, and Sperman's correlation and multivariate logistic regression analysis. A high dental plaque index and a high prevalence of periodontitis (48.3%), mostly in moderate and localized chronic form, were observed. Individuals with periodontitis presented higher levels of IL-1 and MMP-2, while individuals with cardiovascular disease (CVD) and individuals with two or more systemic diseases (MSD) presented higher levels of IL-1; diabetes mellitus (DM) and MSD individuals presented higher levels of IL-6. A positive association was found between the severity of periodontitis and CVD (OR 2.2; CI = 1.11-4.42). This study reported a 48.3% of the prevalence of periodontitis in ICU patients and a positive association between the severity of periodontitis and CVD. Additionally, higher levels of IL-1 and MMP-2 were found in individuals with periodontitis, higher levels of IL-6 were found in individuals with DM, and higher levels of IL-1 were found in individuals with CVD.

Periodontal condition and immunological aspects of individuals hospitalized in the intensive care unit

Abstract There are few studies on the clinical and immunological periodontal status of intensive care unit (ICU) in-patients. The aim of the present study was to evaluate the periodontal condition among ICU in-patients through clinical and immunological periodontal parameters. From the sample of 373 hospitalized ICU patients, 182 were submitted' to a thorough clinical periodontal and immunological evaluation. Data on bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) were collected and gingival sulcular fluid samples were quantified through ELISA on IL-1, IL-6, and MMP-2 for immunological evaluation. Data was statistically analyzed by Chi-square, Fisher's exact, Mann-Whitney tests, and Sperman's correlation and multivariate logistic regression analysis. A high dental plaque index and a high prevalence of periodontitis (48.3%), mostly in moderate and localized chronic form, were observed. Individuals with periodontitis presented higher levels of IL-1 and MMP-2, while individuals with cardiovascular disease (CVD) and individuals with two or more systemic diseases (MSD) presented higher levels of IL-1; diabetes mellitus (DM) and MSD individuals presented higher levels of IL-6. A positive association was found between the severity of periodontitis and CVD (OR 2.2; CI = 1.11-4.42). This study reported a 48.3% of the prevalence of periodontitis in ICU patients and a positive association between the severity of periodontitis and CVD. Additionally, higher levels of IL-1 and MMP-2 were found in individuals with periodontitis, higher levels of IL-6 were found in individuals with DM, and higher levels of IL-1 were found in individuals with CVD.

Resumo Existem poucos estudos sobre o estado clínico periodontal e imunológico de pacientes em unidade de terapia intensiva (UTI). O objetivo do presente estudo foi avaliar a condição periodontal entre os pacientes internados na UTI através de parâmetros clínicos periodontais e imunológicos. De uma amostra inicial de 373 pacientes internados em UTI, 183 foram submetidos a exame periodontal completo e análise imunológica. Os dados sobre o sangramento na sondagem (BOP), profundidade de sondagem (PD) e nível clínico de inserção (CAL) foram coletados e as amostras de fluido sulcular gengival foram quantificadas para avaliação imunológica através de ELISA para IL-1, IL-6 e MMP-2. Os dados foram analisados estatisticamente pelos testes de Qui-quadrado, exato de Fischer, Mann-Whitney, correlação de Sperman e análise de regressão logística multivariada. Foi observado um alto índice de placa dental e uma alta prevalência de periodontite (48,3%), principalmente na forma crônica moderada e localizada. Os indivíduos com periodontite apresentaram níveis mais altos de IL-1 e MMP-2, enquanto indivíduos com doença cardiovascular (CVD) e com mais de duas doenças sistêmicas (MSD) apresentaram níveis mais altos de IL-1 e os com diabetes mellitus (DM) e MSD apresentaram níveis mais elevados de IL-6. Foi encontrada associação positiva entre a gravidade da periodontite e CVD (OR 2.2; IC = 1,11-4,42). Este estudo reportou uma prevalência de periodontite em 48.3% dos pacientes em UTI e uma associação positiva entre ocorrência de periodontite e CVD. Além disso, níveis mais elevados de IL-1 e MMP-2 foram encontrados em indivíduos com periodontite, de IL-6 em indivíduos com DM e de IL-1 em indivíduos com CVD.

IgG sera levels against a subset of periodontopathogens and severity of disease in aggressive periodontitis patients: a cross-sectional study of selected pocket sites.

AIMS: To evaluate the association among serum immunoglobulin G (IgG) responses to Aggregatibacter actinomycetemcomitans (Aa) serotypes a, b and c, Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf) and clinical parameters in Aggressive Periodontitis (AP) subjects. Associations between periodontal pathogens and clinical and immunological parameters were also evaluated. METHODS: Thirty-eight subjects diagnosed with generalized AP (GAP) and localized AP (LAP) were included. Ten healthy controls were also evaluated. Clinical parameters were assessed and percentages of subgingival levels of Aa, Pg and Tf (beyond bacterial load), were determined by quantitative real-time polymerase chain reaction. Serum IgG antibody levels against Aa, Pg and Tf were evaluated by enzyme-linked immunosorbent assay. RESULTS: Percentages of Aa, Pg and Tf were significantly higher in AP than in controls. The response to Aa serotype c was higher in LAP subjects than in controls. There were no differences in microbial composition or antibodies responses between GAP and LAP, except for IgG response to Tf. Pg levels were correlated with probing depth (PD), BoP and CAL in GAP but not in LAP subjects. Tf levels correlated with PD and CAL in GAP subjects. In GAP, the infection levels of Aa and Pg correlated with the corresponding IgG levels to Aa serotype c and Pg. CONCLUSION: Given the evidences that IgG response in AP patients correlated with bacterial infection level in GAP, but not in LAP, and that LAP patients lack a response to Tf, despite harbouring this species, our data suggest a difference in host immune defence between these two forms of aggressive periodontitis.

Relationship between chemokines and dendritic cells in human chronic periodontitis.

BACKGROUND: The purpose of this study was to evaluate the relationship between chemokines and dendritic cells (DCs) in human chronic periodontitis (CP). METHODS: Gingival samples were obtained from 23 individuals with CP, and six samples of normal mucosa (NM) overlapping the third molar were used to control for the chemokine levels. Periodontal examination was conducted. Immunohistochemistry was performed for Factor XIIIa(+) and cluster of differentiation (CD)1a(+) immature DCs and CD83(+) mature DCs. Levels of the CC chemokine ligand (CCL)2, CCL3, CCL5, CCL19, CCL20, and CXC chemokine ligand (CXCL)8 were measured in gingival tissues using enzyme-linked immunosorbent assay. Inflammatory infiltrate, DCs, chemokines, classification of human CP, and clinical parameters were correlated and compared. RESULTS: The expression of CCL2 and CCL20 was positively correlated with increased densities of CD1a(+) DCs. CCL3 and CXCL8 were positively related to the clinical attachment level. CCL3, CCL5, CCL19, and CXCL8 levels increased in the gingival samples of patients with CP compared with NM, whereas CCL20 levels increased in advanced CP compared with mild-moderate CP. CONCLUSIONS: More CD1a(+) immature DCs are related to CCL2 and CCL20. CCL3 and CXCL8 chemokines are related to a greater severity of human CP.

Evaluation of the host response in various models of induced periodontal disease in mice.

BACKGROUND: The aim of this study is to characterize and evaluate the host response caused by three different models of experimental periodontitis in mice. METHODS: C57BL/6 wild-type female mice were distributed into six experimental groups and sacrificed at 7, 15, and 30 days after the induction of periodontal disease: 1) group C: no treatment control group; 2) group L: periodontal disease induced by ligature; 3) group G-Pg: oral gavage with Porphyromonas gingivalis (Pg); 4) group G-PgFn: oral gavage with Fusobacterium nucleatum + Pg; 5) group I-Pg: heat-killed Pg injected into the palatal mucosa between the molars; and 6) group I-V: phosphate-buffered saline injected into the palatal mucosa. The samples were used to analyze the immune-inflammatory process in the gingival tissue via descriptive histologic and real-time polymerase chain reaction analyses. The alveolar bone loss was evaluated using microcomputed tomography. The data were analyzed using the Kruskal-Wallis test, followed by a post hoc Dunn test and analysis of variance, followed by a Tukey test using a 5% significance level. RESULTS: Only the ligature model displayed significant alveolar bone loss in the initial period (7 days), which was maintained with time. The group injected with heat-killed Pg displayed significant alveolar bone loss starting from day 15, which continued to progress with time (P <0.05). A significant increase (P <0.05) in the gene expression of proinflammatory cytokines (interleukin-6 and -1ß) and proteins involved in osteoclastogenesis (receptor activator of nuclear factor-κB ligand and osteoprotegerin) was observed in the ligature group on day 7. CONCLUSION: The ligature and injection of heat-killed Pg models were the most representative of periodontal disease in humans, whereas the oral gavage models were not effective at inducing the disease under the experimental conditions.

Immunophenotyping in saliva as an alternative approach for evaluation of immunopathogenesis in chronic periodontitis.

BACKGROUND: To date, flow cytometric immunophenotyping has not been used to investigate immune patterns in saliva samples from individuals with inflammatory processes in the oral cavity, such as chronic periodontitis (CP). Saliva analysis could be a non-invasive method for evaluating oral health. The objective of this study is to determine the phenotype of leukocytes and total immunoglobulin A (IgA), IgG, and IgM titers in the saliva of individuals with CP. METHODS: Saliva samples were obtained from patients with CP (n = 12) and from a control group (n = 27) without oral diseases. Flow cytometry was performed to determine the frequency of T cells (CD4(+) and CD8(+)), B cells, and natural killer (NK) cells as well as the total leukocyte population. Immunoglobulin titers were determined by dot enzyme-linked immunosorbent assay. RESULTS: Cell immunophenotyping revealed that patients with CP had a higher frequency of total leukocytes (47.94% ± 5.1%; P < 0.001), B cells (43.93% ± 6.2%; P = 0.006), NK cells (0.16% ± 0.04%; P = 0.03), and CD4(+) T cells (38.99% ± 4.4%; P = 0.002) than individuals without oral pathologies (24.75% ± 2.2%, 20.60% ± 2.7%, 0.09% ± 0.03%, and 16.82% ± 3.5%, respectively). No significant differences in salivary total IgA, IgG, and IgM titers were found between the two cohorts studied. Nevertheless, higher total IgG levels were observed in patients with CP, which could indicate a possible correlation between clinical attachment level and salivary IgG (P = 0.07; r(2) = 0.08). CONCLUSION: These results show that cell phenotyping by flow cytometry could be an effective tool for determining leukocyte profiles in saliva samples from patients with CP and healthy individuals.

Interferon-γ, interleukins-6 and -4, and factor XIII-A as indirect markers of the classical and alternative macrophage activation pathways in chronic periodontitis.

BACKGROUND: Macrophages account for 5% to 30% of the inflammatory infiltrate in periodontitis and are activated by the classic and alternative pathways. These pathways are identified by indirect markers, among which interferon (IFN)-γ and interleukin-6 (IL)-6 of the classic pathway and IL-4 of the alternative pathway have been studied widely. Recently, factor XIII-A (FXIII-A) was reported to be a good marker of alternative pathway activation. The aim of this study is to determine the macrophage activation pathways involved in chronic periodontitis (CP) by the detection of the indirect markers IFN-γ, IL-6, FXIII-A, and IL-4. METHODS: Biopsies were taken from patients with CP (n = 10) and healthy individuals (n = 10) for analysis of IFN-γ, IL-6, IL-4, and FXIII-A by Western blot (WB), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). The same biopsies of healthy and diseased gingival tissue were used, and the expressions of these markers were compared between healthy individuals and those with CP. RESULTS: The presence of macrophages was detected by CD68+ immunohistochemistry and their IFN-γ, IL-6, IL-4, and FXIII-A markers by WB, IHC, and ELISA in all samples of healthy and diseased tissue. IL-6, IL-4, and FXIII-A were significantly higher in patients with CP, whereas FXIII-A was higher in healthy individuals. CONCLUSION: The presence of IFN-γ, IL-6, IL-4, and FXIII-A in healthy individuals and in patients with CP suggests that macrophages may be activated by both classic and alternative pathways in health and in periodontal disease.

Porphyromonas gingivalis, Treponema denticola and toll-like receptor 2 are associated with hypertensive disorders in placental tissue: a case-control study.

AIM(S): To explore the associations between the presence of periodontal pathogens and the expression of toll-like receptors (TLR-2 and TLR-4) in the placental tissue of patients with hypertensive disorders compared to the placentas of healthy normotensive patients. MATERIAL AND METHODS: A case-control study was performed. From a cohort composed of 126 pregnant women, 33 normotensive healthy pregnant women were randomly selected, and 25 cases of patients with hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, were selected. Placental biopsy was obtained after aseptic placental collection at the time of delivery. All of the samples were processed and analysed for the detection of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Treponema denticola and Tannerella forsythia using the polymerase chain reaction (PCR) technique. Determination of the expressions of TLR-2 and TLR-4 was performed in samples of total purified protein isolated from placental tissues and analysed by ELISA. The data were assessed using descriptive statistics. The associations among variables were estimated through multiple logistic regression models and the Mann-Whitney test to evaluate the differences between the two groups. RESULTS: A significant increase was observed in the expression of TLR-2 in the placentas of patients with hypertensive disorders (p = 0.04). Additionally, the multiple logistic regression models demonstrated an association between the presence of T. denticola and P. gingivalis in placental tissues and hypertensive disorders (OR: 9.39, p = 0.001, CI 95% 2.39-36.88 and OR: 7.59, p = 0.019, CI 95% 1.39-41.51, respectively). CONCLUSIONS: In the present study, pregnant women with periodontal disease presented an association in the placental tissue between the presence of T. denticola and P. gingivalis and hypertensive disorders. Additionally, increased expression of TLR-2 was observed. However, further studies are required to determine the specific roles of periodontal pathogens and TLRs in the placental tissue of patients with pregnancy-related hypertensive disorders.

Relationship between salivary leukotriene B4 levels and salivary mucin or alveolar bone resorption, in subjects with periodontal health and disease.

OBJECTIVE: Here we determine the salivary levels of leukotriene B4 (LTB4 ) and its relation with salivary mucin and alveolar bone level. BACKGROUND: LTB4 is a membrane-derived lipid mediator formed from arachidonic acid. It is among the most potent stimulants of polymorphonuclear leukocytes providing the first host defense against infections. Leukotrienes also induce bone resorption. Because LTB4 is present in the oral cavity the aim of the present study was to explore the role of LTB4 in patients with periodontal disease. METHODS: Eighty-one subjects were clinically examined and distributed into four groups, namely, clinically healthy, mild, moderate and severe periodontitis, according to periodontal status, classified into values of clinical attachment level and probing pocket depth. Unstimulated saliva was collected for 5 min. Salivary LTB4 was determined by an immune assay method, mucin was determined by a colorimetric method and radiographic assessment used to determine alveolar bone level. RESULTS: Patients with mild periodontitis showed a decrease in salivary LTB4 levels while patients with severe periodontitis showed increased LTB4 levels. A significant positive correlation was observed between salivary LTB4 and clinical attachment level, salivary mucin concentration or alveolar bone level. CONCLUSION: The close relation between salivary LTB4 and mucin levels suggested that LTB4 might be involved in the defense mechanism of the oral cavity. The correlation of LTB4 with the alveolar bone level indicates that they are one of the mediators responsible for bone resorption.

Association of CD28 and CTLA-4 gene polymorphisms with aggressive periodontitis in Brazilians.

OBJECTIVE: Susceptibility to and severity of periodontal disease is influenced by gene polymorphisms related to the immune response. Co-stimulatory molecules, such as CD28 and CTLA-4, are critical in the development of such responses. Our hypothesis is that polymorphisms in genes that code for these molecules may be associated with periodontitis. The aim of the study was to investigate the association between +17 (T/C) CD28 and +49 (A/G) CTLA-4 gene polymorphisms and periodontitis in Brazilians. MATERIALS AND METHODS: Genomic DNA was obtained from oral swabs of 424 individuals categorized into three groups (control group, aggressive, and chronic periodontitis) considering clinical parameters such as probing depth and clinical attachment loss. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There was an association between the T(-) genotype of the CD28 polymorphism and aggressive periodontitis (P = 0.04). Moreover, the A(+) genotype for CTLA-4 was associated with greater clinical attachment loss in non-smokers with aggressive periodontitis (P = 0.006, OR = 16.25, CI = 2.25-117.11). CONCLUSIONS: These findings show that T(-) in CD28 + 17 (T/C) and the A(+) in CTLA-4 +49 (A/G) genotypes are associated with susceptibility to aggressive periodontal disease. Thus, our study highlights these polymorphisms as potential genetic susceptibility markers of periodontitis in Brazilians.

Effectiveness of non-surgical treatment to reduce il-18 levels in the gingival crevicular fluid of patients with periodontal disease.

The aim of this study was to evaluate the effectiveness of the non-surgical periodontal treatment in reducing the gingival crevicular fluid (GCF) levels of IL-18 from inflamed periodontal sites. Fourteen patients with periodontal disease were included, being 9 patients with chronic periodontitis (mean age: 48.8 SD ± 7.4 years) and 5 patients with gingivitis (mean age: 43.6 SD ± 11.8). The patients were divided in the following groups: gingivitis sites from periodontitis patients (sites GP), periodontitis sites from periodontitis patients (sites PP), and gingivitis sites from gingivitis patients (sites GG). Probing pocket depth (PPD), probing attachment level (AL), plaque index (PI) and gingival index (GI) were recorded, and gingival fluid samples were collected. The subjects received non-surgical treatment and were re-evaluated 30 days after treatment (day 30 AT). There was a significant reduction in PI in GG (1.0 ± 0.4 to 0.5 ± 0.2), GP (1.2 ± 0.3 to 0.5 ± 0.3), and in PP (1.3 ± 0.4 to 0.7 ± 0.3) 30 AT. There was also a significant reduction in the GI in GG (1.3 ± 0.3 to 0.7 ± 0.4). PPD reduced significantly in GG (2.4 ± 0.6 to 1.9 ± 0.1), and PP (6.7 ± 1.1 to 5.2 ± 0.9) 30 AT. When all the samples were analyzed together, there was a significant reduction in IL-18 (12.9 ± 7.2 to 10.0 ± 3.1). This study showed that non-surgical treatment was effective in reducing GCF levels of IL-18 from inflamed periodontal sites.

Effects of periodontal therapy on phagocytic activity of peripheral blood neutrophils - evidence for an extrinsic cellular defect.

PURPOSE: To compare phagocytic activity of peripheral blood neutrophils from subjects with and without periodontal disease and evaluate the effects of periodontal therapy in individuals with similar levels of resolution of inflammation at the end of treatment. MATERIALS AND METHODS: To compare the phagocytic activity of neutrophils, peripheral blood was collected from 27 control subjects with a healthy periodontium and 28 periodontitis subjects before and after treatment. The phagocytosis of killed Saccharomyces cerevisiae, pre-sensitised or non-sensitised with fresh serum from the donor, was quantified and a phagocytic index was calculated as the mean number of yeast cells phagocytised by the percentage of neutrophils involved in phagocytosis. RESULTS: Prior to periodontal treatment, subjects with periodontitis exhibited significantly lower neutrophil phagocytic activity than control subjects with a healthy periodontium. Periodontal treatment significantly improved in clinical periodontal status and resulted in significantly increased phagocytosis of both pre-sensitised (from 113.0 pre- to 157.0 post-treatment, P = 0.02) and non-sensitised S. cerevisiae (from 1.5 pre- to 3.5 post-treatment, P = 0.001), to levels observed in control subjects. CONCLUSIONS: The phagocytic activity of peripheral blood neutrophils from subjects with periodontal disease was lower than that of healthy controls. Subjects who underwent non-surgical periodontal treatment and strict supportive therapy for 6 months showed improved phagocytic activity in peripheral blood neutrophils. The phagocytic index values from subjects with periodontal disease after treatment achieved those found in the control group.

A.actinomycetemcomitans-induced periodontal disease promotes systemic and local responses in rat periodontium.

AIM: To characterize the histologic and cellular response to A. actinomycetemcomitans (Aa) infection. MATERIAL & METHODS: Wistar rats infected with Aa were evaluated for antibody response, oral Aa colonization, loss of attachment, PMN recruitment, TNF-α in the junctional epithelium and connective tissue, osteoclasts and adaptive immune response in local lymph nodes at baseline and 4, 5 or 6 weeks after infection. Some groups were given antibacterial treatment at 4 weeks. RESULTS: An antibody response against Aa occurred within 4 weeks of infection, and 78% of inoculated rats had detectable Aa in the oral cavity (p < 0.05). Aa infection significantly increased loss of attachment that was reversed by antibacterial treatment (p < 0.05). TNF-α expression in the junctional epithelium followed the same pattern. Aa stimulated high osteoclast formation and TNF-α expression in the connective tissue (p < 0.05). PMN recruitment significantly increased after Aa infection (p < 0.05). Aa also increased the number of CD8(+) T cells (p < 0.05), but not CD4(+) T cells or regulatory T cells (Tregs) (p > 0.05). CONCLUSION: Aa infection stimulated a local response that increased numbers of PMNs and TNF-α expression in the junctional epithelium and loss of attachment. Both TNF-α expression in JE and loss of attachment was reversed by antibiotic treatment. Aa infection also increased TNF-α in the connective tissue, osteoclast numbers and CD8(+) T cells in lymph nodes. The results link Aa infection with important characteristics of periodontal destruction.

Interleukin-21 expression and its association with proinflammatory cytokines in untreated chronic periodontitis patients.

BACKGROUND: Interleukin-21 (IL-21) controls the differentiation of T-helper Th17 cells and induces the production of IL-17 in this T-cell subtype. The aim of this study is to determine the relative expression of IL-21 in gingival tissues of chronic periodontitis patients and correlate/associate this expression with proinflammatory cytokines and clinical parameters of disease. METHODS: Samples of gingival biopsies were collected from chronic periodontitis patients (n = 10) and controls (n = 8). The mRNA expressions of IL-21, IL-1ß, IL-6, IL-17, IL-23, IL-10, and transforming growth factor-ß1 (TGF-ß1) were quantified using real-time reverse transcription-polymerase chain reaction. IL-21 levels were compared between chronic periodontitis and healthy gingival tissues and correlated with cytokine and clinical parameters of tissue destruction. RESULTS: A significant overexpression of IL-21, IL-1ß, IL-6, IL-17, and IL-23p19 was detected in periodontal disease-affected tissues compared to healthy gingival tissues. IL-10 and TGF-ß1 were, however, downregulated in periodontal lesions. IL-21 yielded significant positive correlations with probing depth, clinical attachment level, IL-1ß, and IL-6. In addition, IL-21 was negatively correlated with IL-10 and TGF-ß1. CONCLUSIONS: IL-21 was overexpressed in chronic periodontitis gingival tissues and correlated with clinical parameters of periodontal destruction and with proinflammatory cytokines. Therefore, IL-21 might play a role in the tissue destruction that characterizes chronic periodontal disease.

Role of anti-ß1 adrenergic antibodies from patients with periodontitis in cardiac dysfunction.

BACKGROUND: The presence of serum autoantibodies against ß(1) adrenoreceptors (ß(1)-ARs) in human gingival fibroblast from patients with periodontitis inhibits primary cell-specific growth and induces over-expression of pro-inflammatory mediators. Serum ß(1)-AR autoantibodies from patients with periodontitis react with myocardium and modify cardiac contractility. The relationship between the presence of serum ß(1)-AR autoantibodies and alterations in heart rate variability (HRV) was also studied. METHODS: An enzyme-linked immunosorbent assay (ELISA) using cardiac and gingival fibroblast membranes or synthetic peptides corresponding to the second extracellular loop of human ß(1)-AR was used to detect serum autoantibodies. The HRV was assessed from RR interval files generated from 22:00 to 08:00 hours. The autoantibody effects on contractility were measured on spontaneous rat isolated atria. RESULTS: Circulating autoantibodies from 36 patients with periodontitis and 20 healthy individuals (controls) interacted with fibroblasts, the cardiac surface, and ß(1)-AR synthetic peptides. The distributions of serum antibodies against gingival and myocardium membranes and ß(1)-AR synthetic peptide were 88.8%, 77.7%, and 92.8%, respectively. Moreover, 88.5% of patients with periodontitis whose sera were positive against ß(1)-AR synthetic peptide had decreased HRV. The corresponding affinity-purified anti-ß(1)-AR peptide IgG displayed partial agonist-like activity modifying the isolated atria contractility. CONCLUSION: This manuscript describes that patients with periodontitis showed increased levels of serum IgG with reactive activity against ß(1)-AR. Those patients demonstrated decrease in heart rate, and IgG derived from their sera induced aberrant contractility of heart atrium. We propose that periodontitis increases the risk of cardiovascular diseases, although it increases anti-ß(1)-AR autoantibody that alters myocardial contractility.

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.

Effectiveness of non-surgical treatment to reduce il-18 levels in the gingival crevicular fluid of patients with periodontal disease

The aim of this study was to evaluate the effectiveness of the non-surgical periodontal treatment in reducing the gingival crevicular fluid (GCF) levels of IL-18 from inflamed periodontal sites. Fourteen patients with periodontal disease were included, being 9 patients with chronic periodontitis (mean age: 48.8 SD ± 7.4 years) and 5 patients with gingivitis (mean age: 43.6 SD ± 11.8). The patients were divided in the following groups: gingivitis sites from periodontitis patients (sites GP), periodontitis sites from periodontitis patients (sites PP), and gingivitis sites from gingivitis patients (sites GG). Probing pocket depth (PPD), probing attachment level (AL), plaque index (PI) and gingival index (GI) were recorded, and gingival fluid samples were collected. The subjects received non-surgical treatment and were re-evaluated 30 days after treatment (day 30 AT). There was a significant reduction in PI in GG (1.0 ± 0.4 to 0.5 ± 0.2), GP (1.2 ± 0.3 to 0.5 ± 0.3), and in PP (1.3 ± 0.4 to 0.7 ± 0.3) 30 AT. There was also a significant reduction in the GI in GG (1.3 ± 0.3 to 0.7 ± 0.4). PPD reduced significantly in GG (2.4 ± 0.6 to 1.9 ± 0.1), and PP (6.7 ± 1.1 to 5.2 ± 0.9) 30 AT. When all the samples were analyzed together, there was a significant reduction in IL-18 (12.9 ± 7.2 to 10.0 ± 3.1). This study showed that non-surgical treatment was effective in reducing GCF levels of IL-18 from inflamed periodontal sites.

O objetivo desse estudo foi avaliar o efeito do tratamento periodontal não-cirúrgico sobre os níveis da IL-18 em sítios inflamados de pacientes com doença periodontal. Foram avaliados 14 pacientes com doença periodontal, sendo 9 pacientes com periodontite crônica generalizada (idade média: 48,8 DP ± 7,4 anos) e 5 pacientes com gengivite (idade média: 43,6 DP ± 11,8 anos). Os pacientes foram divididos nos seguintes grupos: sítios sem perda de inserção nos pacientes com periodontite (GP), sítios com perda de inserção nos pacientes com periodontite (PP) e sítios sem perda de inserção nos pacientes com gengivite (GG). Profundidade de bolsa (PB), nível de inserção (NI), índice de placa (IP) e índice gengival (IG) foram avaliados e amostras do fluido gengival foram coletadas. Os pacientes receberam terapia não-cirúrgica e foram reavaliados 30 dias após tratamento (AT). Houve uma redução significante no IP dos GG (1,0 ± 0,4 para 0,5 ± 0,2), GP (1,2 ± 0,3 para 0,5 ± 0,3) e PP (1,3 ± 0,4 para 0,7 ± 0,3) 30 AT. Também houve uma redução significante no IG do GG (1,3 ± 0,3 para 0,7 ± 0,4). A profundidade de bolsa reduziu no GG (2,4 ± 0,6 para 1,9 ± 0,1) e no PP (6,7 ± 1,1 para 5,2 ± 0,9) 30 AT. Quando todas as amostras foram analisadas juntas, houve uma redução significante do IL-18 (12,9 ± 7,2 para 10,0 ± 3,1). Esse estudo mostrou que a terapia periodontal não-cirúrgica é eficaz em reduzir os níveis de IL-18 no fluido gengival de sítios inflamados.

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.

Effect of non-surgical treatment on chronic and aggressive periodontitis: clinical, immunologic, and microbiologic findings.

BACKGROUND: Our goal was to examine differences in clinical, microbiologic, and immunologic responses to non-surgical mechanical therapy in patients with generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAgP). METHODS: Twenty patients with GCP and 14 patients with GAgP were evaluated. Clinical data, gingival crevicular fluid (GCF), and subgingival plaque samples were collected at baseline and 3 months after non-surgical periodontal treatment. Levels of 40 subgingival species were measured using checkerboard DNA-DNA hybridization. GCF interleukin (IL)-1ß, -4, and -8 and interferon-γ (IFN-γ) were analyzed using a multiplexed bead immunoassay, and elastase activity was measured using an enzymatic assay. The significance of changes with time was examined using the Wilcoxon rank sum test. Changes in clinical, microbiologic, and immunologic parameters after therapy were compared between groups using the Mann-Whitney U test. RESULTS: After periodontal therapy, we found significant improvements for all clinical parameters in both groups. We also observed significant reductions in elastase activity in shallow and deep sites from the GAgP group and in deep sites from the GCP group. Microbiologic data showed significant reductions in proportions of orange and red complexes and an increase in proportions of Actinomyces species in both clinical groups. When the clinical, microbiologic, and immunologic responses after therapy were compared between groups, only minor differences were found. CONCLUSION: This study fails to show any significant differences between severe forms of GCP and GAgP in response to non-surgical periodontal treatment.

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.