RESUMO
OBJECTIVE: To evaluate the effects of Bifidobacterium animalis subsp. lactis HN019 (HN019) on clinical periodontal parameters (plaque accumulation and gingival bleeding), on immunocompetence of gingival tissues [expression of beta-defensin (BD)-3, toll-like receptor 4 (TLR4), cluster of differentiation(CD)-57 and CD-4], and on immunological properties of saliva (IgA levels) in non-surgical periodontal therapy in generalized chronic periodontitis (GCP) patients. Adhesion to buccal epithelial cells (BEC) and the antimicrobial properties of HN019 were also investigated. MATERIALS AND METHODS: Thirty patients were recruited and monitored clinically at baseline (before scaling and root planing-SRP) and after 30 and 90 days. Patients were randomly assigned to Test (SRP+Probiotic, n = 15) or Control (SRP+Placebo, n = 15) group. Probiotic lozenges were used for 30 days. Gingival tissues and saliva were immunologically analyzed. The adhesion of HN019 with or without Porphyromonas gingivalis in BEC and its antimicrobial properties were investigated in in vitro assays. Data were statistically analyzed (p<0.05). RESULTS: Test group presented lower plaque index (30 days) and lower marginal gingival bleeding (90 days) when compared with Control group. Higher BD-3, TLR4 and CD-4 expressions were observed in gingival tissues in Test group than in Control group. HN019 reduced the adhesion of P. gingivalis to BEC and showed antimicrobial potential against periodontopathogens. CONCLUSION: Immunological and antimicrobial properties of B. lactis HN019 make it a potential probiotic to be used in non-surgical periodontal therapy of patients with GCP. CLINICAL RELEVANCE: B. lactis HN019 may be a potential probiotic to improve the effects of non-surgical periodontal therapy. Name of the registry and registration number (ClinicalTrials.gov): "Effects of probiotic therapy in the treatment of periodontitis"-NCT03408548.
Assuntos
Bifidobacterium animalis/imunologia , Periodontite Crônica/terapia , Probióticos/uso terapêutico , Adulto , Aderência Bacteriana/imunologia , Infecções por Bacteroidaceae/imunologia , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/terapia , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Método Duplo-Cego , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunoglobulina A Secretora/metabolismo , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Porphyromonas gingivalis/patogenicidade , Saliva/imunologiaRESUMO
BACKGROUND: The relationship between periodontitis and the pathogenesis of other inflammatory diseases, such as diabetes, rheumatoid arthritis and obesity has been an important topic of study in recent decades. The Th17 pathway plays a significant role in how local inflammation can influence systemic inflammation in the absence of systemic pathology. OBJECTIVE: To determine Th17 biased-cells in systemically healthy patients in the presence of generalized chronic periodontitis. METHODOLOGY: A total of 28 patients were recruited without systemic inflammatory pathology, which was determined by clinical history, the Health Assessment Questionnaire (HAQ) and rheumatoid factor detection. Of these patients, 13 were diagnosed as healthy/gingivitis (H/G) and 15 as generalized chronic periodontitis (GCP). Th17 (CD4+CD161+) cells and Th17IL23R+ (CD4+CD161+IL-23R+) cells were quantified by flow cytometry, based on the total cells and on the lymphocyte region, termed the "enriched population" (50,000 events for each). RESULTS: The percentages of Th17 cells of the H/G and periodontitis groups were similar on total cells and enriched population (19 vs 21.8; p=4.134 and 19.6 vs 21.8; p=0.55). However, Th17IL23R+ cells differ significantly between periodontally healthy patients and generalized chronic periodontitis patients in both total cell (0.22% vs 0.65%; p=0.0004) and enriched populations (0.2% vs 0.75%; p=0.0266). CONCLUSIONS: GCP patients (otherwise systemically healthy) were characterized by increased Th17-proinflammatory cell phenotype positive for the IL-23 receptor in peripheral blood. The proportion of Th17 cells that are negative for the IL-23 receptor in the peripheral blood of systemically healthy patients seemed to be unaffected by the presence or absence of chronic periodontitis.
Assuntos
Periodontite Crônica/imunologia , Células Th17/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Periodontite Crônica/patologia , Feminino , Citometria de Fluxo , Gengivite/imunologia , Gengivite/patologia , Humanos , Interleucina-23/sangue , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Fenótipo , Receptores de Interleucina/sangue , Estatísticas não Paramétricas , Inquéritos e Questionários , Células Th17/patologia , Adulto JovemRESUMO
Abstract The relationship between periodontitis and the pathogenesis of other inflammatory diseases, such as diabetes, rheumatoid arthritis and obesity has been an important topic of study in recent decades. The Th17 pathway plays a significant role in how local inflammation can influence systemic inflammation in the absence of systemic pathology. Objective: To determine Th17 biased-cells in systemically healthy patients in the presence of generalized chronic periodontitis. Methodology: A total of 28 patients were recruited without systemic inflammatory pathology, which was determined by clinical history, the Health Assessment Questionnaire (HAQ) and rheumatoid factor detection. Of these patients, 13 were diagnosed as healthy/gingivitis (H/G) and 15 as generalized chronic periodontitis (GCP). Th17 (CD4+CD161+) cells and Th17IL23R+ (CD4+CD161+IL-23R+) cells were quantified by flow cytometry, based on the total cells and on the lymphocyte region, termed the "enriched population" (50,000 events for each). Results: The percentages of Th17 cells of the H/G and periodontitis groups were similar on total cells and enriched population (19 vs 21.8; p=4.134 and 19.6 vs 21.8; p=0.55). However, Th17IL23R+ cells differ significantly between periodontally healthy patients and generalized chronic periodontitis patients in both total cell (0.22% vs 0.65%; p=0.0004) and enriched populations (0.2% vs 0.75%; p=0.0266). Conclusions: GCP patients (otherwise systemically healthy) were characterized by increased Th17-proinflammatory cell phenotype positive for the IL-23 receptor in peripheral blood. The proportion of Th17 cells that are negative for the IL-23 receptor in the peripheral blood of systemically healthy patients seemed to be unaffected by the presence or absence of chronic periodontitis.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Periodontite Crônica/imunologia , Células Th17/imunologia , Fenótipo , Estudos de Casos e Controles , Índice Periodontal , Inquéritos e Questionários , Receptores de Interleucina/sangue , Estatísticas não Paramétricas , Interleucina-23/sangue , Periodontite Crônica/patologia , Células Th17/patologia , Citometria de Fluxo , Gengivite/imunologia , Gengivite/patologiaRESUMO
Background: Chronic periodontitis (CP), caused by bacteria and fungi, appears in up to 66% of HIV-patients. The impact and association of HIV-treatment (HAART) and Candida itself has not been properly evaluated in the development and progression of CP. The immunopathogenesis is characterized by CD4+ T-cells activation and the balance between the T-helper 1 (Th1) and T-helper 2 (Th2) or a mixed cytokine profile. Currently, the associated causes of an immune response in HIV-patients with CP is controversial. Our aims were the determination of Candida spp. and cytokine profile in oral samples from HIV-positive patients with CP, considering the CD4+ T cells levels and HAART use. Methods: From 500 HIV-positive patients evaluated, 228 patients were enrolled. Patients were separated in groups: (A) n = 53 (≤200 CD4+ T-cells on HAART); (B) n = 57 (≤200 CD4+ T-cells without HAART); (C) n = 50 (>200 CD4+ T-cells without HAART); (D) n = 68 (>200 CD4+ T-cells on HAART). Candida spp. were isolated from the oral biofilm and crevicular fluid in CHROMagar and confirmed by endpoint PCR. Cytokine levels were measured by beads-based immunoassay in saliva by flow cytometry. Results: 147 patients (64.5%) were positive to Candida spp. and 204 strains were isolated; 138 (67.6%) were C. albicans and the remaining C. non-albicans species (C. glabrata>C. tropicalis>C. krusei>C. dubliniensis). In this study, CHROMagar showed good sensitivity (95%) but poor specificity (68%); since of the 152 samples identified as C. albicans, only 131 were confirmed by PCR; from the 10 samples identified as C. glabrata, only six were confirmed. Finally, of the 42 samples detected as C. tropicalis, only five were confirmed. When evaluating Candida spp. presence, group A and D had higher isolation, while group B had the highest species diversity. Whereas, group C had a significant reduction of Candida spp. Despite the presence of Candida and HAART, we found a Th1/Th2 hybrid profile in the saliva of patients with low CD4+ T-cell count (group A). Conclusion: Abundance and diversity of the Candida spp. detected in HIV-patients with CP could be related to HAART and low CD4+ T-cells levels. Also, the immunosuppression might promote a local Th1/Th2 hybrid cytokine profile.
Assuntos
Candida/imunologia , Candidíase Bucal/imunologia , Periodontite Crônica/imunologia , Citocinas/imunologia , Infecções por HIV/imunologia , Células Th1/imunologia , Células Th2/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Candida/classificação , Candida/fisiologia , Candidíase Bucal/microbiologia , Periodontite Crônica/microbiologia , Periodontite Crônica/virologia , Citocinas/metabolismo , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Saliva/efeitos dos fármacos , Saliva/imunologia , Saliva/metabolismo , Especificidade da Espécie , Células Th1/microbiologia , Células Th1/virologia , Células Th2/microbiologia , Células Th2/virologiaRESUMO
Periodontitis is characterized by a chronic inflammation produced in response to a disease-associated multispecies bacterial community in the subgingival region. Although the inflammatory processes occur locally in the oral cavity, several studies have determined that inflammatory mediators produced during periodontitis, as well as subgingival species and bacterial components, can disseminate from the oral cavity, contributing therefore, to various extraoral diseases like cancer. Interestingly, carcinogenesis associated with periodontal species has been observed in both the oral cavity and in extra oral sites. In this review, several studies were summarized showing a strong association between orodigestive cancers and poor oral health, presence of periodontitis-associated bacteria, tooth loss, and clinical signs of periodontitis. Proinflammatory pathways were also summarized. Such pathways are activated either by mono- or polymicrobial infections, resulting in an increase in the expression of proinflammatory molecules such as IL-6, IL-8, IL-1ß, and TNF-α. In addition, it has been shown that several periodontitis-associated species induce the expression of genes related to cell proliferation, cell cycle, apoptosis, transport, and immune and inflammatory responses. Intriguingly, many of these pathways are linked to carcinogenesis. Among them, the activation of Toll-like receptors (TLRs) and antiapoptotic pathways (such as the PI3K/Akt, JAK/STAT, and MAPK pathways), the reduction of proapoptotic protein expression, the increase in cell migration and invasion, and the enhancement in metastasis are addressed. Considering that periodontitis is a polymicrobial disease, it is likely that mixed species promote carcinogenesis both in the oral cavity and in extra oral tissues and probably-as observed in periodontitis-synergistic and/or antagonistic interactions occur between microbes in the community. To date, a good amount of studies has allowed us to understand how monospecies infections activate pathways involved in tumorigenesis; however, more studies are needed to determine the combined effect of oral species in carcinogenesis.
Assuntos
Carcinogênese/imunologia , Carcinogênese/metabolismo , Periodontite Crônica/imunologia , Periodontite Crônica/metabolismo , Inflamação/metabolismo , Animais , Citocinas/metabolismo , HumanosRESUMO
Chronic periodontitis (CP) is an infection that affects the teeth supporting structure. Macrophage migration inhibitory factor (MIF) is an important effector cytokine of the innate immune system. Due to its functional characteristics, MIF may be involved in the immunopathology of CP. The aim of the present study was to evaluate MIF levels in gingival crevicular fluid (GCF), saliva, and serum of CP patients. A cross-sectional study was conducted on 60 subjects divided into two groups: subjects with CP (n= 30) and periodontally healthy subjects without CP (n=30). MIF was quantified in GCF, saliva, and serum of all participants by enzyme-linked immunosorbent assay. MIF concentrations were higher in GCF, saliva, and serum in the group with CP compared with the group without CP and a higher MIF concentration was observed in GCF (p=0.001) and saliva (p=0.009) in the group with CP. MIF intragroup comparisons between fluids demonstrated significant high levels of MIF in saliva compared with GCF and serum in both study groups (p<0.05). A positive correlation was found between clinical signs and MIF concentration in GCF (p<0.05). There is an association between the MIF and the clinical signs of the disease. Therefore, MIF could have an important role in the pathology and progression of CP.
Assuntos
Periodontite Crônica/genética , Periodontite Crônica/metabolismo , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Adulto , Periodontite Crônica/sangue , Periodontite Crônica/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Líquido do Sulco Gengival/imunologia , Líquido do Sulco Gengival/metabolismo , Humanos , Oxirredutases Intramoleculares/química , Oxirredutases Intramoleculares/imunologia , Fatores Inibidores da Migração de Macrófagos/química , Fatores Inibidores da Migração de Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Saliva/imunologia , Saliva/metabolismoRESUMO
RESUMEN Introducción: Para la Organización Mundial de la Salud, la enfermedad periodontal representa un problema de salud pública en países industrializados y en los que están en vías de desarrollo. Afecta la calidad de vida de quienes las sufren. Este término agrupa una serie de entidades que afectan los tejidos de protección e inserción del diente, dentro de las cuales se encuentra la periodontitis, proceso inmunoinflamatoria crónico. Objetivo: estimar la prevalencia de la enfermedad periodontal inmunoinflamatoria crónica en el municipio de Jovellanos, provincia de Matanzas. Materiales y métodos: con el objetivo de estimar la prevalencia de la enfermedad periodontal inmunoinflamatoria crónica, en el municipio de Jovellanos, provincia de Matanzas se realizó un estudio observacional, descriptivo transversal, en el período comprendido entre el mes junio del 2009 a junio del 2010. Resultados: el 54,5 % de la población no presentó la enfermedad estudiada. El grupo de 5 a 11 años fue el que más aportó a este resultado. La enfermedad fue diagnosticada en el 45,5 % de la población examinada, la cual comenzó a manifestarse a partir del grupo de edad de 15 a 18 años. El 92,9 % de los individuos de 60 a 74 años fueron los más afectados. Conclusiones: en cuanto a la enfermedad periodontal inmuno inflamatoria la cantidad de pacientes sanos, desde el punto de vista periodontal, estuvo entre un 49,4 % y un 59,6 % del total de la población. La incidencia de la enfermedad aumenta con la edad. La presencia de bolsas resultó mayor a partir de los 35 años y causó gran afectación en los individuos de 60 a 74 años.
ABSTRACT Introduction: According to the World Health Organization, periodontal disease represents a public health problem in the developed countries and in the developing ones. It affects the life quality of people suffering it. This term groups together several entities affecting the tooth´s insertion and protection tissues; periodontitis, a chronic immunoinflammatory process, is found among them. Objective: estimate the prevalence of periodontal disease inmunoinflamatoria chronic in the municipality of Jovellanos, province of Matanzas. Materials and methods: a cross-sectional descriptive, observational study was carried out in the municipality of Jovellanos, province of Matanzas from June 2009 to June 2010 for the sake of estimating the prevalence of the chronic immunoinflammatory periodontal disease. Results: 54.5 % of the population did not present the studied disease. The 5-11-years-old group was the one contributing more to these results. The disease was diagnosed in 45.5 % of the studied population, and started to manifest beginning from the 15-18-years-old age group. 92.9 % of the individuals aged 60 to 74 years were the most affected ones. Conclusions: from the periodontal point of view, the quantity of healthy patients oscillated between 49.4 % and 59.6 % of the total population. The disease incidence increases with age. The presence of pockets was higher from the age of 35 years on, and caused great affectation in individuals aged 60-74 years.
Assuntos
Humanos , Fatores de Risco , Periodontite Crônica/imunologia , Periodontite Crônica/epidemiologia , Gengivite/imunologia , Gengivite/epidemiologia , Doenças Periodontais/imunologia , Doenças Periodontais/epidemiologia , Epidemiologia Descritiva , Estudos Transversais , Estudo ObservacionalRESUMO
OBJECTIVES: The immune system has an important role in the development of systemic lupus erythematosus (SLE) and chronic periodontitis (CP). Altered cytokines levels characterise both diseases and contributes to periodontal tissue damage in CP and to macrocomplexes deposition with connective tissue destruction in SLE. This study aimed to evaluate the production of salivary cytokines in patients with SLE and its association with periodontal status. METHODS: The sample comprised 70 SLE patients and 70 paired controls. SLE activity and damage were scored using Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Subjects were classified as without or with CP. Salivary concentrations of IL-33, MMP2/TIMP2, RANK and OPG were measured by ELISA, while IL-2, IFNγ, TNFα, IL-4, IL-6, IL-10 and IL-17A were determined by Cytometric Bead Array. Linear regression models analysed association among SLE, CP and salivary cytokines. RESULTS: IL-6 and IL-17A concentrations were significantly higher in SLE/CP patients than controls/CP. Concentrations of IL-6, IL-17A and IL-33 were increased in SLE/CP individuals when compared to SLE without CP. Multivariate model revealed association of cumulative dose of corticoids with periodontal damage and of IL-33 salivary concentration with SLE activity. CONCLUSIONS: Our findings suggest that long-term therapy with corticoids would contribute with periodontal destruction in SLE patients. Moreover, the increased levels of IL-6, IL-17A and IL-33 in saliva of SLE subjects with CP may signal it as possible inflammatory pathways in this process.
Assuntos
Periodontite Crônica/imunologia , Citocinas/análise , Lúpus Eritematoso Sistêmico/imunologia , Saliva/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , HumanosRESUMO
Individuals carrying the ATC/TTC haplotype (Hap-1) in the interleukin 8 (IL8) gene were reported as more susceptible to chronic periodontitis (CP), an infectious disease associated with Gram-negative bacteria, in comparison to patients with the ATT/TTC haplotype (Hap-2). This study investigated the functionality of the IL8 haplotypes in lymphocytes and monocytes of individuals carrying the Hap-1 or Hap-2 IL8 haplotypes in the response to CP-associated Gram-negative bacteria (periodontopathogens). Peripheral blood was collected from 6 subjects carrying each haplotype, and their immune cells were challenged with periodontopathogens or phorbol 12-myristate 13-acetate (PMA) plus Ionomycin. Depending on the immune cell type (lymphocytes or monocyte-derived macrophages) the assessed outcomes were: phenotypical polarization, gene expression, phagocytic activity, chemotaxis and production of reactive oxygen species (ROS). Subjects carrying the Hap-1 haplotype showed increased expression of IL8 and TNFA and significantly skewing towards pro-inflammatory Th1/M1/Th17 phenotypes. There was increased percentage of ROS-producing monocyte-derived macrophages from individuals carrying the Hap-1 haplotype. Cells from individuals presenting the Hap-2 haplotype had an overall attenuated response to periodontopathogens, with a significant shift towards the Treg phenotype. In conclusion, the IL8 haplotypes showed to be functional both in monocyte-derived macrophages and lymphocytes. The Hap-1 haplotype previously associated with increased susceptibility to CP demonstrated greater skewing to pro-inflammatory Th1/M1/Th17 phenotypes and production of ROS.
Assuntos
Periodontite Crônica , Bactérias Gram-Negativas/imunologia , Bactérias Gram-Negativas/patogenicidade , Interleucina-8/genética , Linfócitos/metabolismo , Macrófagos/metabolismo , Aggregatibacter actinomycetemcomitans/imunologia , Aggregatibacter actinomycetemcomitans/patogenicidade , Periodontite Crônica/genética , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Feminino , Predisposição Genética para Doença , Infecções por Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/imunologia , Haplótipos , Humanos , Interleucina-8/metabolismo , Linfócitos/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Fenótipo , Porphyromonas gingivalis/imunologia , Porphyromonas gingivalis/patogenicidadeRESUMO
The inflammatory cytokines involved in the immune response to chronic periodontal disease (CPD) in the context of leprosy reactions (LR) were analyzed in 57 new cases of multibacillary leprosy (MBL). They were stratified by the presence of CPD and LR. Messenger RNA (mRNA) expression of inflammatory mediators was determined by qRT-PCR using skin biopsy and by ELISA using serum samples, maintaining 5% of significance level in ANOVA and correlation analyses. Twenty-three (40.4%) patients presented the first LR, whereas 22 (45.0%) patients presented CPD. IL-4 and IL-6 serum levels were significantly lower in patients with CPD and LR than in patients without CPD but with LR; IFN-γ serum levels were higher in patients with CPD and LR than in patients with no CPD and no LR; IL-4 serum levels were negatively correlated with TNF-α gene expression, while IL-6 serum levels were positively correlated with IFN-γ gene expression, in the skin of subjects with CPD and LR. The presence of DPC in individuals with LR immunoregulated IL-6, IFN-γ, and IL-4 concentrations. The presence of DPC decreased serum levels of IL-6 and IL-4 in reactional individuals. CPD concomitant to LR resulted in increased IFN-γ serum levels.
Assuntos
Periodontite Crônica/genética , Citocinas/imunologia , Hanseníase/complicações , Adulto , Periodontite Crônica/sangue , Periodontite Crônica/imunologia , Citocinas/sangue , Feminino , Humanos , Imunidade Humoral , Hanseníase/sangue , Hanseníase/imunologia , Masculino , Fatores de Risco , Fatores SocioeconômicosRESUMO
BACKGROUND AND OBJECTIVE: Human beta-defensins (hBDs) contribute to innate immunity antimicrobial activity. They are also effective in the adaptive immune response and may play a crucial role in the susceptibility to diseases of the oral cavity. This study aimed to evaluate the levels of hBD-1 in the gingival crevicular fluid of individuals with and without chronic periodontitis. MATERIAL AND METHODS: Twenty periodontally healthy individuals (H) and 20 individuals with chronic periodontitis were recruited. Gingival crevicular fluid samples were collected from: healthy sites (Hh) from periodontally healthy individuals; and healthy sites (Ph), sites with gingivitis (Pg), and sites with periodontitis (Pp) from individuals with periodontitis. The levels of hBD-1 (pg/mL) were measured using enzyme-linked immunosorbent assay. Comparisons of hBD-1 between individuals (H and chronic periodontitis) and among sites (Hh, Ph, Pg, Pp) were performed through hierarchical linear modeling. RESULTS: Gingival crevicular fluid levels of hBD-1 were: Hh = 229.52 ± 138.96 (median 199.26), Ph = 53.88 ± 58.17 (median 35.75), Pg = 57.11 ± 40.18 (median 39.90) and Pp = 55.31 ± 37.28 (median 54.19). No influence of site diagnosis (level 1; health/gingivitis/periodontitis) was observed; however, individual diagnosis (level 2; health/periodontitis) influenced the levels of hBD-1 (P < .001). CONCLUSION: Periodontally healthy individuals showed higher gingival crevicular fluid levels of hBD-1 when compared to individuals with chronic periodontitis. This suggests a potential protective role of hBD-1 in the susceptibility to chronic periodontitis.
Assuntos
Periodontite Crônica/imunologia , Líquido do Sulco Gengival/imunologia , beta-Defensinas/imunologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
This study aimed to evaluate the association between haplotypes in the interleukin 8 (IL8) and IL4 genes previously associated to chronic periodontitis (CP) and the levels of Aggregatibacter actinomycetemcomitans (A.a.) in subgingival sites of patients with and without CP. Moreover, multifaceted evaluations were made to search associations among patients' genetic background with the A.a. levels and previous clinical/immunological/microbiological findings. Subgingival sites (n = 596) of 104 patients were divided into susceptible to CP by the IL8 haplotype ATC/TTC (IL8+); non-susceptible to CP by the IL8 AGT/TTC (IL8-); susceptible to CP by the IL4 TCI/CCI (IL4+); protection against CP by the IL4 TTD/CTI (IL4-). Subgingival biofilm samples from diseased and healthy sites of CP patients and from control sites of health patients were obtained for absolute quantification of A.a. by quantitative real-time polymerase chain reaction. For diseased sites, samples were collected before and 45 days after periodontal treatment. The IL4 but not the IL8 haplotypes were associated with levels of A.a. (in both periods). After periodontal treatment, higher levels of A.a. were found in subgingival sites of (IL4-) patients, and higher levels of IL-4 were associated with deeper probing pockets in these same patients. Significant correlations were found among genetic (patients carrying IL8 or IL4 haplotypes), microbiological and immunological data showing the interrelationship of different factors in the CP.
Assuntos
Aggregatibacter actinomycetemcomitans/genética , Biofilmes/crescimento & desenvolvimento , Periodontite Crônica/genética , Predisposição Genética para Doença , Interleucina-4/genética , Interleucina-8/genética , Polimorfismo Genético , Adulto , Aggregatibacter actinomycetemcomitans/crescimento & desenvolvimento , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Aggregatibacter actinomycetemcomitans/patogenicidade , Carga Bacteriana , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Periodontite Crônica/terapia , Feminino , Expressão Gênica , Haplótipos , Humanos , Interleucina-4/imunologia , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , RNA Ribossômico 16S/genética , Curetagem SubgengivalRESUMO
BACKGROUND AND OBJECTIVE: Two new T-helper (Th) phenotypes have been recently described and named Th9 and Th22 lymphocytes; however, their role in the pathogenesis of periodontitis remains unclear. This study was aimed to assess whether Th9 and Th22 lymphocytes, through interleukin (IL)-9 and IL-22 production, respectively, are associated with the severity of periodontitis and bone resorption. MATERIAL AND METHODS: Gingival crevicular fluid samples and biopsies were obtained from patients with moderate-to-advanced chronic periodontitis and gingivitis, and healthy controls. The levels for the Th9 and Th22-associated cytokines and master-switch transcription factors Spi-B and aryl hydrocarbon receptor (AhR) were quantified by enzyme-linked immunosorbent assay, real-time reverse-transcription quantitative polymerase chain reaction and flow cytometry. In addition, the osteoclast activity in response to tissue homogenates from periodontitis and healthy samples was analyzed quantifying the number of TRAP-positive cells and areas of bone resorption pits produced, in the presence or absence of recombinant human IL-22 and anti-IL-22 neutralization antibody. RESULTS: Higher levels of IL-22 and AhR were detected in patients with periodontitis compared with gingivitis and healthy individuals. In addition, higher levels of IL-9 and Spi-B were detected in gingivitis patients compared with periodontitis and healthy individuals. In patients with periodontitis, a significant positive correlation was detected between secreted levels of IL-22 and clinical attachment level of the sampled periodontal pockets. When osteoclasts were exposed to tissue homogenates obtained from patients with periodontitis, higher levels of resorptive activity were observed as compared with the same cells exposed to tissue homogenates obtained from healthy individuals, and this increment was dependent on the presence and neutralization of IL-22. CONCLUSION: Increased levels of IL-22 produced by Th22 lymphocytes are associated with the pathogenesis of periodontitis, in particular, with osteoclast resorptive activity and severity of disease.
Assuntos
Periodontite Crônica/imunologia , Citocinas/metabolismo , Líquido do Sulco Gengival/química , Interleucinas/metabolismo , Osteoclastos/imunologia , Osteoclastos/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Adulto , Periodontite Crônica/patologia , Citocinas/análise , Citocinas/genética , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/metabolismo , Feminino , Expressão Gênica , Gengivite/imunologia , Gengivite/patologia , Humanos , Interleucina-9/análise , Interleucina-9/metabolismo , Interleucinas/análise , Masculino , Perda da Inserção Periodontal , Bolsa Periodontal/imunologia , RNA/isolamento & purificação , RNA Ribossômico 18S/análise , Receptores de Hidrocarboneto Arílico/análise , Fatores de Transcrição/análise , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Interleucina 22RESUMO
Antimicrobial photodynamic therapy (aPDT) was introduced as a promising adjuvant therapy on the periodontal treatment. The aim of this study was to evaluate the effect of aPDT on inflammatory mediator levels in residual periodontal pockets of patients with severe chronic periodontitis under periodontal maintenance, during 12 months follow-up. A randomized controlled trial study was conducted in 28 patients with severe chronic periodontitis. After non-surgical periodontal treatment, patients with at least four teeth with residual pocket probing depth (PPD) ≥4 mm were randomly assigned to either aPDT or control group. The aPDT (low power laser: 660 nm, 40 mW, 90 J/cm2, methylene blue 0.01 %) was performed at baseline and 3, 6, and 9 months. Clinical parameters were collected before and 3 and 12 months after the intervention, and gingival crevicular fluid was collected in the same times, including 1 week after the intervention. Immunological evaluation was carried out using the Luminex assay which quantified the expression of ten cytokines: interleukin (IL)-1α, IL-1ß, IL-8, IL-1ra, fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-4, and IL-10. All clinical variables showed significant improvement for both groups, but there was no statistical difference between groups with no clinical benefits. IL-1α, IL-1ß, IL-8, and VEGF showed significant differences (p < 0.05) between groups, whereas IL-1ra mediators, IFN-γ, and IL-10 demonstrated a statistical difference (p < 0.01) over time in the same group. At any time, FGF, IL-4, and TNF-α showed no statistical difference between groups (p > 0.05). aPDT therapy can improve the benefits on inflammation control during the periodontal maintenance.
Assuntos
Periodontite Crônica/tratamento farmacológico , Periodontite Crônica/imunologia , Mediadores da Inflamação/metabolismo , Fotoquimioterapia , Adulto , Idoso , Estudos de Casos e Controles , Periodontite Crônica/metabolismo , Periodontite Crônica/patologia , Citocinas/metabolismo , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Periodontitis is a multifactorial disease, with participation of bacterial, environmental, and host factors. It results from synergistic and dysbiotic multispecies microorganisms, critical "keystone pathogens," affecting the whole bacterial community. The purpose of this study was to review the role of Porphyromonas gingivalis in the immunopathogenesis of chronic periodontitis, with special attention paid to HmuY. The host response during periodontitis involves the innate and adaptive immune system, leading to chronic inflammation and progressive destruction of tooth-supporting tissues. In this proinflammatory process, the ability of P. gingivalis to evade the host immune response and access nutrients in the microenvironment is directly related to its survival, proliferation, and infection. Furthermore, heme is an essential nutrient for development of these bacteria, and HmuY is responsible for its capture from host heme-binding proteins. The inflammatory potential of P. gingivalis HmuY has been shown, including induction of high levels of proinflammatory cytokines and CCL2, decreased levels of IL-8, and increased levels of anti-HmuY IgG and IgG1 antibodies in individuals with chronic periodontitis. Therefore, the HmuY protein might be a promising target for therapeutic strategies and for development of diagnostic methods in chronic periodontitis, especially in the case of patients with chronic periodontitis not responding to treatment, monitoring, and maintenance therapy.
Assuntos
Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Infecções por Bacteroidaceae/imunologia , Infecções por Bacteroidaceae/metabolismo , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Porphyromonas gingivalis/imunologia , Porphyromonas gingivalis/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Fatores de Virulência/imunologia , Fatores de Virulência/metabolismoRESUMO
During periodontitis, alveolar bone resorption is associated with activation of T helper type 17 (Th17) lymphocytes and receptor activator of nuclear factor-κB ligand (RANKL) -induced osteoclasts. We previously reported that serotype b of Aggregatibacter actinomycetemcomitans has a higher capacity to trigger Th17-type differentiation and function in activated T lymphocytes and its lipopolysaccharide is a more potent immunogen compared with the other serotypes. This study aimed to investigate whether serotype b of A. actinomycetemcomitans induces higher Th17-associated RANKL production, RANKL-induced osteoclast activation, and antigen-specific memory T lymphocyte proliferation. On naive CD4(+) T lymphocytes stimulated with autologous dendritic cells primed with different A. actinomycetemcomitans serotypes, RANKL production, T-bet, GATA-3, RORC2 and Foxp3 expression, RORC2/RANKL intracellular double-expression, TRAP(+) osteoclast activation, and bone resorption were quantified. The frequency of proliferating memory T lymphocytes in response to A. actinomycetemcomitans serotypes was determined in periodontitis and healthy subjects. Naive CD4(+) T lymphocytes stimulated by serotype b-primed dendritic cells elicited higher levels of RANKL, RORC2, TRAP(+) osteoclasts, and bone resorption than the same cells stimulated with the other serotypes. RANKL positively correlated and co-expressed with RORC2. Memory T lymphocytes responding to serotype b were more frequently detected in periodontitis patients than healthy subjects. These results indicate that serotype b of A. actinomycetemcomitans is associated with higher production of RANKL and these increased levels are associated with Th17 lymphocyte induction, osteoclast activation, and bone resorption.
Assuntos
Aggregatibacter actinomycetemcomitans/imunologia , Osteoclastos/imunologia , Linfócitos T/imunologia , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Diferenciação Celular/imunologia , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Células Dendríticas/imunologia , Fatores de Transcrição Forkhead/biossíntese , Fator de Transcrição GATA3/biossíntese , Humanos , Memória Imunológica/imunologia , Lipopolissacarídeos/farmacologia , Ativação Linfocitária , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/biossíntese , Ligante RANK/imunologia , Sorogrupo , Linfócitos T/microbiologiaRESUMO
AIM: Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and are an important group of hypolipidaemic drugs, widely used in the treatment of hypercholesterolaemia and cardiovascular disease. Some studies have shown that statins are able to modulate inflammation and alveolar bone loss. METHODS: In order to evaluate whether statins could influence periodontal treatment, improving the clinical and radiographic parameters in chronic periodontitis, a systematic review was conducted in the databases PUBMED and BIREME, searching for articles in English and Portuguese, published between the years 2004 and 2014, using the combined keywords statin, periodontal disease, periodontitis and alveolar bone. Studies regarding the treatment of chronic periodontitis in humans, blind or double-blind, retrospective cohort or randomized controlled trials that used statins topically or systemically were selected. RESULTS: Statins have important anti-inflammatory and immune effects, reducing levels of C-reactive protein and matrix metalloproteinases and their intermediate products, such as tumour necrosis factor-α, and are also able to inhibit the adhesion and extravasation of leukocytes, which block the co-stimulation of T cells. Statins reduce bone resorption by inhibiting osteoclast formation and lead to increased apoptosis of these cells. The effect of statins on bone formation is related to the increased gene expression of bone morphogenetic protein in osteoblasts. CONCLUSION: Although we found biological mechanisms and clinical results that show lower alveolar bone loss and reduction of clinical signs of inflammation, further studies are needed to evaluate the clinical applicability of statins in the routine treatment of chronic periodontitis.
Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Periodontite Crônica/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Proteína Morfogenética Óssea 2/metabolismo , Periodontite Crônica/diagnóstico , Periodontite Crônica/genética , Periodontite Crônica/imunologia , Periodontite Crônica/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Osteoprotegerina/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Genetic markers associated with disease are often non-functional and generally tag one or more functional "causative" variants in linkage disequilibrium. Markers may not show tight linkage to the causative variants across multiple ethnicities due to evolutionary divergence, and therefore may not be informative across different population groups. Validated markers of disease suggest causative variants exist in the gene and, if the causative variants can be identified, it is reasonable to hypothesize that such variants will be informative across diverse populations. The aim of this study was to test that hypothesis using functional Interleukin-1 (IL-1) gene variations across multiple ethnic populations to replace the non-functional markers originally associated with chronic adult periodontitis in Caucasians. MATERIAL AND METHODS: Adult chronic periodontitis cases and controls from four ethnic groups (Caucasians, African Americans, Hispanics and Asians) were recruited in the USA, Chile and China. Genotypes of IL1B gene single nucleotide polymorphisms (SNPs), including three functional SNPs (rs16944, rs1143623, rs4848306) in the promoter and one intronic SNP (rs1143633), were determined using a single base extension method or TaqMan 5' nuclease assay. Logistic regression and other statistical analyses were used to examine the association between moderate to severe periodontitis and IL1B gene variations, including SNPs, haplotypes and composite genotypes. Genotype patterns associated with disease in the discovery study were then evaluated in independent validation studies. RESULTS: Significant associations were identified in the discovery study, consisting of Caucasians and African Americans, between moderate to severe adult chronic periodontitis and functional variations in the IL1B gene, including a pattern of four IL1B SNPs (OR = 1.87, p < 0.0001). The association between the disease and this IL1B composite genotype pattern was validated in two additional studies consisting of Hispanics (OR = 1.95, p = 0.04) or Asians (OR = 3.27, p = 0.01). A meta-analysis of the three populations supported the association between the IL-1 genotype pattern and moderate to severe periodontitis (OR 1.95; p < 0.001). Our analysis also demonstrated that IL1B gene variations had added value to conventional risk factors in predicting chronic periodontitis. CONCLUSION: This study validated the influence of IL-1 genetic factors on the severity of chronic periodontitis in four different ethnicities.
Assuntos
Periodontite Crônica/imunologia , Etnicidade/genética , Variação Genética/genética , Interleucina-1beta/genética , Adulto , Negro ou Afro-Americano/genética , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Chile/etnologia , China/etnologia , Periodontite Crônica/genética , Estudos de Coortes , Feminino , Genótipo , Haplótipos/genética , Hispânico ou Latino/genética , Humanos , Indígenas Sul-Americanos/genética , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Estados Unidos/etnologia , População Branca/genéticaRESUMO
BACKGROUND AND OBJECTIVE: Microbiological and immunological hypotheses have been raised to explain the differences in the clinical manifestations of aggressive periodontitis and chronic periodontitis. However, studies comparing the cytokine/chemokine profiles in gingival crevicular fluid between these two clinical conditions have so far not been compiled. This systematic review aimed to answer the following question: "Do subjects with aggressive periodontitis and chronic periodontitis have a different profile of cytokines/chemokines in the gingival crevicular fluid?" MATERIAL AND METHODS: An electronic database search of MEDLINE/PubMed and Embase was performed from 1990 up to and including August 2013, using MeSH terms and other keywords. Titles and abstracts were screened and the papers that satisfied eligibility criteria were assessed. RESULTS: Of 1954 titles, 17 studies reporting the levels of 21 different cytokines/chemokines were included. Most studies did not find any significant differences in the gingival crevicular fluid levels of cytokines/chemokines between aggressive periodontitis and chronic periodontitis. Some studies demonstrated that the levels of specific proinflammatory and anti-inflammatory cytokines/chemokines were higher (n = 5) and lower (n = 3), respectively, in aggressive periodontitis than in chronic periodontitis. The studies differed in the manner in which they reported the results (e.g. concentrations or total amounts). It was not clear in some studies whether the sample sites from both groups were matched for disease severity. Some studies did not take into account confounders, such as smoking. CONCLUSION: The current weight of evidence is not sufficient to prove that there are distinct gingival crevicular fluid cytokine/chemokine profiles for patients with aggressive periodontitis and chronic periodontitis.
Assuntos
Periodontite Agressiva/imunologia , Quimiocinas/análise , Periodontite Crônica/imunologia , Citocinas/análise , Líquido do Sulco Gengival/imunologia , Líquido do Sulco Gengival/química , Humanos , Mediadores da Inflamação/análise , Interleucinas/análiseRESUMO
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.