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-6、IL-33、IL-10在牙周炎和类风湿关节炎中的表达和相关性分析

目的: 检测牙周炎和类风湿关节炎患者龈沟液中白介素6（interleukin-6,IL-6）、白介素33（interleukin-33,IL-33）、白介素10（interleukin-10,IL-10）的含量,并探讨IL-6、IL-33、IL-10与牙周炎和类风湿关节炎2种疾病的相关关系。方法: 按纳入标准,选取就诊于中国医科大学附属盛京医院口腔科及风湿免疫科的患者,其中牙周炎组21例（PD组）,类风湿关节炎组21例（RA组）,类风湿关节炎合并牙周炎组24例（PD + RA组）,健康对照者24例（H组）。记录4组受试者一般信息、牙周探诊深度（periodontal probing depth,PPD）、临床附着丧失（clinical attachment loss,CAL）、龈沟出血指数（sulcus bleeding index, SBI）。收集各组受试者龈沟液样本,应用酶联免疫吸附试验测定IL-6、IL-33、IL-10的含量,并对4组受试者IL-6、IL-33、IL-10含量与牙周指标进行相关性分析。采用SPSS 20.0 软件包对数据进行统计学分析。结果: IL-6在PD+RA组的表达水平显著高于H组、PD组和RA组（P<0.05）; PD组、RA组、PD+RA组IL-33的含量显著高于H组（P<0.05）,PD+RA组IL-33的含量显著高于RA组(P<0.05);RA组IL-10的表达水平显著高于H组、PD组和PD+RA组(P<0.05)。PD组PPD与IL-6、IL-33的含量呈正相关（r=0.62, 0.43）,PD+RA组SBI、PPD、CAL与IL-33含量呈正相关（r=0.69,0.58,0.55）。结论: 牙周炎伴发类风湿关节炎患者龈沟液中IL-6、IL-33水平显著升高,IL-10含量显著降低,推测IL-6、IL-33和IL-10在牙周炎和类风湿关节炎的发生、发展中具有重要作用。     

Simvastatin decreases IL-6 and IL-8 production in epithelial cells

Many cardiovascular studies have suggested that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors (statins) have anti-inflammatory effects independent of cholesterol lowering. As a chronic inflammatory disease, periodontitis shares some mechanisms with atherosclerosis. Since oral epithelial cells participate importantly in periodontal inflammation, we measured simvastatin effects on interleukin-6 and interleukin-8 production by cultured human epithelial cell line (KB cells) in response to interleukin-1alpha. Simvastatin decreased production, an effect reversed by adding mevalonate or geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate. Simvastatin was found to reduce NF-kappaB and AP-1 promoter activity in KB cells. Dominant-negative Rac1 severely inhibited interleukin-1alpha-induced NF-kappaB and AP-1 promoter activity. Our results may indicate an anti-inflammatory effect of simvastatin on human oral epithelial cells, apparently involving Rac1 GTPase inhibition.     

Expression of IL-6, IL-10, IL-17 and IL-33 in the peri-implant crevicular fluid of patients with peri-implant mucositis and peri-implantitis

ObjectivesThe aim of this study was to compare the levels of IL-6, IL-10, IL-17 and IL-33 in the peri-implantar crevicular fluid (PICF) and in parotid gland saliva (PGS) of healthy patients, and peri-implantitis and peri-implant mucositis patients.Materials and methodsThe PICF was collected from 40 implants as follows: 10 peri-implant mucositis patients, 20 peri-implantitis patients and 10 healthy patients. The PICF and PGS samples collected from each patient were quantified for IL-6, IL-10, IL-17 and IL-33 by enzymatic immunosorbent assay (ELISA).ResultsIL-6, IL-17 and IL-33 levels on PIFC were significantly higher in peri-implantitis group when compared to healthy group. IL-17 and IL-33 levels in PIFC were significantly higher in peri-implant mucositis group than in healthy group. There was no significant difference when comparing IL-6, IL-10, IL-17 and IL-33 levels in PGS among healthy, peri-implant mucositis and peri-implantitis groups.ConclusionsTherefore, as in patients with peri-implantitis there were significantly higher levels of IL-6, IL-17 and IL-33 in PICF, we believe that these cytokines were intensifying local inflammatory process, and contributing to clinical aspects such as increased marginal bleeding and probing depth found in patients with peri-implantitis. Furthermore, as IL-17 and IL-33 were increased in patients with peri-implant mucositis, hypothesized that these cytokines were also contributing to the inflammatory process observed in this disease.     

An update on HIV and periodontal disease

With the advent of newer pharmacological approaches to the treatment of human immunodeficiency virus (HIV) infection, the incidence and progression of both atypical and conventional periodontal diseases are changing. The incidence of necrotizing periodontitis and gingival diseases of fungal origin appears to be on the decline as a result of these therapies that have led to increased life spans for HIV patients. However, in cases where these therapies lose their effectiveness and HIV patients relapse into an immunosuppressed state, these conditions may recur. Recent evidence has shown that HIV patients with more conventional periodontal diseases such as chronic periodontitis may have increased attachment loss and gingival recession when compared to their HIV-negative counterparts. This pattern of loss of periodontal support may be due in part to a diffuse invasion of opportunistic bacterial infections, viruses, and fungi into the gingival tissue, leading to a more elevated and more diffuse destructive inflammatory response in the periodontal soft and hard tissues. While the accepted approaches to treating the spectrum of periodontal diseases in HIV patients remain essentially unchanged over the past 15 years, the impact of newer systemic therapies on patient immunocompetence may influence treatment decisions.     

Investigation of functional gene polymorphisms IL-1beta, IL-6, IL-10 and TNF-alpha in individuals with recurrent aphthous stomatitis

Recurrent aphthous stomatitis (RAS) is characterized by recurrent episodes of oral ulceration in an otherwise healthy individual. Some reports in the literature indicate that RAS may have immunological, psychological, genetic and microbiological bases. OBJECTIVE: The purpose of the present study was to investigate, using binary logistic regression analyses, a possible association between the functional IL-1beta +3954 (C/T), IL-6 -174 (G/C), IL-10 -1082 (G/A) and TNF-alpha -308 (G/A) genetic polymorphism and RAS in a sample of Brazilian patients, using a multivariate statistical analysis. DESIGN: Sixty-four consecutive subjects affected by minor and major forms of RAS and 64 healthy volunteers were genotyped. To investigate the association between the single nucleotide polymorphisms and risk of RAS, binary logistic regression models were fitted. The associations were expressed by odd ratios (ORs) and adjusted for age and gender, with the corresponding 95% CIs. P-values less than 0.05 were considered significant. RESULTS: A significant increase in the IL-1beta and TNF-alpha heterozygous genotypes were associated with an increased risk of RAS development (OR 2.40 and 3.07, respectively), in the multivariate model. CONCLUSION: Our findings demonstrate that polymorphisms of high IL-1beta and TNF-alpha production were associated with an increased risk of RAS development. Our findings also give additional support to a genetic basis for RAS pathogenesis.     

Mechanical deformation inhibits IL-10 and stimulates IL-12 production by mouse calvarial osteoblasts in vitro

The skeleton is continuously remodelled throughout life, a process that is orchestrated by cells of the osteoblast lineage. Remodelling involves a complex network of cell-cell signalling involving systemic hormones, locally produced cytokines, growth factors and the mechanical environment of the cells. Here, we report on the effect of mechanically-induced strain on the synthesis by mouse calvarial osteoblasts in monolayer culture of IL-10 and IL-12, two cytokines that inhibit osteoclast formation in bone marrow cultures; IL-10 also suppresses osteoblast differentiation suggesting a role for both cytokines in bone physiology. A tensile strain was applied to the cells intermittently for 6s, every 90s, for 2-96h. After 2-h culture, supernatants from deformed cells contained significantly less IL-10 than control cultures. In contrast, mechanical deformation had a stimulatory effect on IL-12 synthesis; however, by 48h both had returned to control levels. These data suggest that IL-10 and IL-12 can be added to the growing list of mechanical stress-responsive genes. The down-regulation of IL-10 and stimulation of IL-12 further suggests that the initial response of the cells to mechanical deformation was an osteogenic one.     

Polymorphisms in the IL-10 and IL-12 gene cluster and risk of developing recurrent aphthous stomatitis

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common, painful, ulcerative condition of the mouth. Although there is no clear genetic mode of inheritance, there is evidence that inheritance of specific gene polymorphisms may predispose individuals to RAS. AlsoTh1 cell mediated immune responses under the control of IL-10/IL-12 are thought to play an important role in its pathogenesis. OBJECTIVE: The objective of this study was to investigate the possibility that susceptibility to RAS is associated with the inheritance of specific gene polymorphisms for the T cell regulatory cytokines interleukin-10 (IL-10) and interleukin-12 (IL-12). PATIENTS AND METHODS: One hundred RAS patients and 91 ethnically matched controls were genotyped for the IL-10-592, and -1082 polymorphisms, and the IL-12 1188 polymorphism. Chi-square analysis was used to compare the allele frequencies and genotypes of cases and controls. RESULTS: No significant association was identified between inheritance of specific alleles or genotypes of the IL-10-592 and -1082 polymorphisms or IL-12 1188 polymorphism and susceptibility to RAS. CONCLUSIONS: We were unable to demonstrate an association between the inheritance of specific IL-10 or IL-12 gene polymorphisms and RAS susceptibility.     

IL-6 and IL-8 levels in GCF of the teeth supporting fixed partial denture

Objectives:  To evaluate the gingival crevicular fluid (GCF) contents of interleukin-6 (IL-6) and interleukin-8 (IL-8) and the clinical parameters of the teeth supporting fixed partial denture (FPD) and the contralateral teeth and to assess the effect of scaling and root planning (SRP) on clinical parameters and the GCF levels of cytokines.
Materials and methods:  The study population included 23 patients. Probing depth (PD), clinical attachment level (CAL), plaque index (PI), and gingival index (GI) were recorded, and GCF samples were collected for analysis of cytokine levels from the teeth with FPD (Test Group), the contralateral teeth (Control Group) of each participant at baseline. After initial measurements, all participants received primary phase of non-surgical treatment including oral hygiene instruction and scaling and root planning (SRP). At the 1st month and the 3rd month after SRP, these procedures were repeated.
Results:  In both groups, all clinical parameters and the total amount of IL-8 showed decreases from initial to the 3rd month ( P  < 0.05), but from the 1st month to the 3rd month; PD, PI, and GI values significantly increased in the test group ( P  < 0.05).
Conclusion:  The non-surgical periodontal treatment reduced the total amount of IL-8, not IL-6, and the clinical parameters of the teeth with FPD and contralateral teeth. But, there was a trend to the higher levels of PD, PI, and GI in the teeth with FPD. Therefore, a regular program for dental prophylaxis is also important for the maintenance of periodontal health in patients with FPD.     

Impact of SARS-CoV-2 on saliva: TNF-⍺, IL-6, IL-10, lactoferrin,lysozyme, IgG,IgA, and IgM

ObjectivesUnderstanding the role of certain salivary components, such as TNF-?, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM, in airway defense during the ongoing SARS-CoV-2 pandemic is essential. The salivary immune barrier of patients with COVID-19 may play a role in their prognosis. The present study aims to evaluate the impact of SARS-CoV-2 on saliva composition.MethodsA longitudinal study was carried out with male and female firefighters aged 24–48 years. The study sample (n = 34) was divided into 3 groups: asymptomatic volunteers with a negative polymerase chain reaction (PCR) test for SARS-CoV-2 (group 1, Control, n = 21); patients with symptoms of COVID-19 of less than 7 days’ duration and a diagnosis of SARS-CoV-2 infection by PCR (group 2, COVID-19, n = 13); and recovered patients from group 2 who were free of COVID-19 symptoms for at least 2 months (group 3, post-COVID-19 recovery, n = 13). All groups underwent real-time PCR to detect the presence of SARS-CoV-2, as well as analysis of the salivary concentrations of TNF-?, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM by the ELISA method.ResultsLactoferrin concentrations were significantly decreased in the infected group (COVID-19) when compared to those not infected by SARS-CoV-2 (control) (p = 0.032). IgA concentrations were decreased in the COVID-19 and post-COVID-19 groups compared to the control group (p = 0.005 and p = 0.016, respectively). Comparison of the COVID-19 and post-COVID-19 groups also revealed an increase in IgM concentrations during acute SARS-CoV-2 infection (p = 0.010).ConclusionSARS-CoV-2 alters the composition of the salivary immune barrier.     

IL-4- and IL-6-producing cells in human periodontal disease tissue

IL-4- and IL-6-producing cells in human periodontal disease tissues were investigated using immunohistochemical and in situ hybridization techniques. Immunohistochemical analysis demonstrated the presence of IL-4-producing cells within the CD45RO⁺ subset and the percentage of IL-4+ cells was significantly higher in periodontal lesions than in gingivitis tissues (p<0.01). The percentage of IL-6-producing memory cells was higher in periodontal lesions compared with gingivitis tissues, although it was not statistically significant (p<0.05). A reverse tendency in IL-4- and IL-6-positive cells was observed in a few individual cases. No IL-4 mRNA could be detected using the in situ hybridization technique. However, high levels of IL-6 mRNA were present in clinically healthy tissues, with a further increase in both epithelium and connective tissues affected by gingivitis, although only the former was significant (p< 0.025). There was a significant decrease in IL-6 mRNA in both the connective tissue (p<0.025) and epithelium (p<0.01) in periodontitis tissues compared with levels in gingivitis tissues. However, the levels of IL-6 mRNA in periodontal tissues were high compared with those of IL-1 mRNA, which was used in this study as a positive control. These results suggest that Th2–type cells may accumulate in periodontal lesions.     

Suppressive effect of the antimicrobial peptide LL-37 on expression of IL-6, IL-8 and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human gingival fibroblasts

Porphyromonas gingivalis is a major periodontogenic bacterium and possesses immunostimulatory components, such as lipopolysaccharides (LPS) and fimbriae. The host antimicrobial peptide, LL-37, suppresses proinflammatory responses of immune cells but its effect on human gingival fibroblasts (HGFs) is not known. In this study, we assessed the effect of LL-37 on the proinflammatory responses of HGFs stimulated with P. gingivalis cells and their components. Live P. gingivalis cells did not induce proinflammatory responses of HGFs, and LL-37 did not alter these responses. However, LL-37 was able to suppress the killed P. gingivalis cell-induced secretion of interleukin (IL)-6 and IL-8. LL-37 also suppressed the expression of IL6, IL8, and CXCL10 genes that was induced by P. gingivalis components, including phenol-water extracts, lipid A, and fimbriae, and the induction of phosphorylation of p38 and extracellular signal-regulated kinase (ERK) by P. gingivalis lipopolysaccharide (LPS). CAMP was found to be expressed in oral epithelial cells but not in HGFs, despite stimulation with P. gingivalis components. Therefore, LL-37 can exert a suppressive effect on P. gingivalis-induced proinflammatory responses of HGFs in a paracrine manner, suggesting that excess inflammatory responses to P. gingivalis in the gingival tissue are suppressed by LL-37 in vivo.     

Orofacial disease: update for the dental clinical team: 8. Salivary complaints

Certain lesions exclusively or typically affect the salivary glands; these are discussed in this article.     

Capsular polysaccharide from Actinobacillus actinomycetemcomitans inhibits IL-6 and IL-8 production in human gingival fibroblast

We previously reported that a capsular polysaccharide (CP) from Actinobacillus actinomycetemcomitans Y4 induces bone resorption in a mouse organ culture system and osteoclast formation in mouse bone marrow cultures. However, the effects of A. actinomycetemcomitans Y4 CP on human gingival fibroblasts (HGF) are still unclear. The present study was undertaken to test the hypothesis that A. actinomycetemcomitans Y4 CP alters the production of inflammatory cytokines, such as interleukin-6 (IL-6) and IL-8 by HGF. When HGF were cultured with various concentrations of Y4 CP for 24 h, IL-6 and IL-8 production decreased in a concentration-dependent manner. Y4 CP (100 microg/ml) suppressed the release of IL-6 from 9.09 +/- 0.08 ng/ml to 0.34 +/- 0.21 ng/ml (P < 0.01) and IL-8 production decreased from 3.76 +/- 0.03 ng/ml to 0.09 +/- 0.01 ng/ml (P < 0.01). Y4 CP suppressed 70-80% of the release of IL-6 and IL-8 from HGF stimulated with Y4 lipopolysaccharide (LPS), too. Interestingly, anti-A. actinomycetemcomitans Y4 CP completely inhibited the effect of A. actinomycetemcomitans Y4 CP on IL-6 and IL-8 production from HGF. These results indicate that Y4 CP inhibits the release of IL-6 and IL-8 from HGF, suggesting that A. actinomycetemcomitans Y4 modulates the inflammatory response in periodontitis. Remarkably, this inhibitory effect was reversed by specific anti-A. actinomycetemcomitans Y4 CP suggesting an important relationship between the organism and the humoral host response.     

外源性IL-10对炎症牙龈组织中IL-6和ICAM-1表达的影响

目的:探讨外源性IL-10对炎症牙龈组织中IL-6和细胞间粘附分子-1(ICAM-1)表达的影响。方法:采用免疫组化技术检测牙周袋内用或不用IL-10时成人牙周炎患者牙龈组织中IL-6和ICAM-1的表达。结果:IL-6和ICAM-1 均可在炎症牙龈组织的多种细胞表达。IL-6主要表达于淋巴细胞、单核)巨噬细胞、成纤维细胞和内皮细胞。I- CAM-1主要表达于淋巴细胞、上皮细胞、单核)巨噬细胞、成纤维细胞和内皮细胞。使用Image-Proplus软件系统测得的IL-6和ICAM-1表达的IOD值在实验组和对照组间有显著性差异(P<0105)。结论:外源性IL-10对炎症牙龈组织中IL-6和ICAM-1的表达有下调作用。