慢性牙周炎患者治疗前后龈沟液中IL-23、IL-17表达水平的变化

目的研究慢性牙周炎患者牙周基础治疗前后龈沟液(gingival crevicular fluid,GCF)中IL-17、IL-23表达水平的变化,探讨IL-23/IL-17轴在慢性牙周炎发生、发展过程中的作用。方法选取来我科就诊的慢性牙周炎患者50例为研究对象。于牙周基础治疗前后,采集龈沟液并测量体积,运用夹心酶联免疫吸附试验测定IL-17和IL-23的质量浓度以及测量两者之间的关系。结果牙周基础治疗后龈沟液中的IL-17、IL-23表达水平均较治疗前显著下降,差异均有统计学意义(P<0.05)。牙周基础治疗前后龈沟液中的IL-17、IL-23表达水平与牙周临床指标呈正相关。结论 IL-17、IL-23在慢性牙周炎发生发展过程中起重要作用。     

汉族和哈萨克族慢性牙周炎的严重程度与 IL-6和 IL-17相关性分析

纳入新疆木垒地区慢性牙周炎（CP）患者116例,62例汉族组,54例哈萨克族组。以口腔健康的50例汉族,45例哈萨克族为对照。ELISA 检查血液和唾液中 IL-6、IL-17水平。血清与唾液 IL-6和 IL-17水平病例组高于对照组（P ＜0．05）,随 CP 严重程度而升高（P ＜0．05）,哈萨克族病例高于汉族病例组（P ＜0．05）。     

Correlation between salivary IL-1beta levels and periodontal clinical status

OBJECTIVE: To assess the concentration of the proinflammatory cytokine IL-1beta in saliva of periodontally diseased and healthy patients and their relationship with the periodontal status. DESIGN: Unstimulated whole saliva samples from patients with chronic periodontitis (n=30), aggressive periodontitis (n=18) and healthy controls (n=18) were obtained for the study. The periodontal status of each subject was assessed by criteria based on probing depth, clinical attachment loss and the extent/severity of periodontal breakdown. The levels of IL-1beta were measured in saliva samples with a high sensitivity enzyme-linked immunosorbent assay (ELISA). RESULTS: Although no significant difference (P=0.624) was found for salivary IL-1beta levels between periodontitis groups, they were significantly greater (P<0.01) than those detected for healthy controls. Furthermore, Spearman correlation analysis showed statistically significant correlations (P<0.01) between data from salivary IL-1beta levels and clinical measurements. CONCLUSION: The findings of the present study reemphasize the importance of whole saliva as sampling method in terms of immunological purposes in periodontal disease and suggest that the elevated IL-1beta concentration may be one of the host-response components associated to the clinical manifestations of periodontal disease.     

白细胞介素17与牙周炎相关性的研究进展

牙周炎是由牙周致病菌所致的牙周组织慢性炎症性,破坏性疾病。IL-17是一种主要由T细胞产生的促炎因子,参与牙周炎的发生、发展,并可能与牙周炎严重性相关。本文就IL-17参与牙周炎症免疫应答反应及牙槽骨吸收的机制做一综述,旨在阐明IL-17参与牙周疾病的研究现状。     

Association of IL1 gene polymorphisms with chronic periodontitis in Brazilians

Chronic periodontal disease (PD) is an infectious immune-inflammatory illness. Polymorphisms in IL1 genes play a role in inflammatory diseases through the modulation of cytokine levels.

Objective

This study aimed to investigate the association between polymorphisms in the IL1 gene cluster and chronic periodontitis in a Brazilian population.

Design

A sample of 113 subjects over 25 years (mean age 41.2) were grouped into: 44 healthy individuals, 31 subjects with moderate and 38 with severe periodontitis. DNA was obtained through a mouthwash and oral mucosa scraping. PCR-RFLP was used to identify the following polymorphisms: IL1A C − 889T (rs1800587), IL1B C − 511T (rs16944), IL1B C + 3954T (rs11436340), IL1RN intron 2 (rs2234663). Differences in the allele/genotype/haplotype frequencies were assessed by Chi-square test (p < 0.05). The risk associated with alleles, genotypes and haplotypes was calculated as odds ratio (OR) with 95% confidence intervals (CI).

Results

Neither IL1A (C − 889T) nor IL1B (C + 3954T) polymorphisms was associated with chronic PD. Allele T for IL1B (C − 511T) only associated with PD in the group of blacks and mulattos. Moreover, genotype 2/2 for IL1RN (intron 2) was associated with severe PD.

Conclusions

Genotype 2/2 of IL1RN for the whole Brazilian population and allele T of IL1B (C − 511T) in a subgroup of Afro-Americans and mulattos were suggested as putative risk indicators for chronic periodontitis.     

The impact of the IL-11:IL-17 ratio on the chronic periodontitis pathogenesis: a preliminary report

Objective:  An imbalance in the pro- and anti-inflammatory cytokines may be responsible for periodontal breakdown through immune responses. This study aimed to determine the total amount, concentration and ratio of interleukin (IL)-11 and IL-17 in gingival crevicular fluid (GCF) of chronic periodontitis (CP) patients.
Materials and methods:  Forty CP patients and 20 healthy controls (C) were included. The CP group was divided into two subgroups in line with the probing depth (PD) in GCF-sampling sites (CPa: PD ≥ 5 mm, CPb: PD ≤ 4 mm). For each patient, gingival index, plaque index, gingival bleeding time index, PD, and clinical attachment level values were recorded. IL-11 and IL-17 in GCF were evaluated by enzyme-linked immunosorbent assays.
Results:  The total amount and concentration of IL-11 and IL-17 were significantly lower in the CPa group (P <   0.05). The C group has the highest IL-11:IL-17 ratio, followed by CPb and CPa groups respectively. The ratio was significantly lower in CPa group than the CPb and C groups (P <   0.01).
Conclusion:  Our data confirm that the decreased ratio of IL-11:IL-17 may be a factor, which has shown this imbalance between the cytokines' activities in deeper pockets in our study.     

Effect of meloxicam on gingival crevicular fluid IL-1beta and IL1 receptor antagonist levels in subjects with chronic periodontitis, and its effects on clinical parameters

The aim of the present study was to determine the effects of meloxicam after initial periodontal treatment on interleukin-1beta (IL-1β) and IL-1 receptor antagonist (IL-1ra) in gingival crevicular fluid (GCF) and clinical parameters in the chronic periodontitis patients. Data were obtained from 30 patients with chronic periodontitis. Fifteen chronic periodontitis patients received 7.5 mg meloxicam, and 15 patients received placebo tablets in a 1×1 regimen for 1 month. All subjects were nonsmokers and had not received any periodontal therapy. The plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) were recorded. The GCF was collected using a paper strip: eluted and enzyme-linked immunoabsorbent assays (ELISAs) were performed to determine the cytokine levels. The clinical data and GCF samples were obtained after periodontal therapy and 1 month after periodontal therapy. The PI, GI, PD, and GCF IL-1ra decreased significantly (p<0.05) in meloxicam group at first month when comparing the initial levels. While decrease of the PI was statistically significant in control group (p<0.05), statistically significant changes were not determined in the other clinical parameters and GCF cytokine levels (p>0.05). There were no significant differences between two groups in any of the investigated parameters. Our observations did not reveal any influence of meloxicam on levels of IL-1β and IL-1ra in chronic periodontitis. Additional clinical studies are advisable to determine whether COX-2 selective drugs alter periodontal disease outcome with greater safety.     

慢性牙周炎患者牙龈组织中IL-6、IL-34和M-CSFR的表达及临床意义

目的: 比较慢性牙周炎患者牙龈组织和健康牙龈组织中IL-6、IL-34及M-CSFR的表达水平,探讨IL-34 在慢性牙周炎发病中的作用。方法: 收集8例诊断为轻度慢性牙周炎患牙的牙龈组织和8例诊断为重度慢性牙周炎患牙的牙龈组织作为病例组,8例冠延长手术切除的牙龈组织作为对照组,应用实时荧光定量PCR检测IL-6、IL-34及M-CSFR mRNA的表达;应用蛋白免疫印迹检测IL-6、IL-34及M-CSFR蛋白的表达。使用GraphPad Prism 6.0对结果进行统计学分析。结果: IL-6、IL-34、M-CSFR mRNA及蛋白在慢性牙周炎牙龈组织中的表达水平均显著高于正常牙龈组织中的表达（P<0.05）。结论: IL-6、IL-34及M-CSFR的表达可能与慢性牙周炎密切相关。     

不同程度牙周炎自然发展进程与IL-1RN基因多态性的关系

目的 了解慢性牙周炎病程的自然发展及其与IL-1RN（INTRON2）VNTR基因多态性的关系。方法对110例慢性牙周炎患者，其中轻度18例，中度34例，重度58例进行为期6个月的自然病程观察，分别在基线、6个月对全口余留牙牙周袋深度PD、临床附着丧失量AL进行检查，每个牙检查6个位点并检测其IL-1RN（INRON2）VNTR的基因多态性。结果110人平均牙周袋深度增加PD=0．23mm，平均附着丧失量增加AL=0．50mm。其中36例患者44个牙位出现了△AL≥2mm。6个月后PDAL的改变在IL-1RN（INTRON2）VNTR基因型1／1携带者与基因型1／2携带者间无明显差异（P〉0．05）。6个月后IL-1RN（INTRON2）VNTR基因型及等位基因频率在△AL≥2mm组和病情无明显改变组无统计学差异（P〉0．05），重度牙周炎组较轻中度牙周炎组更易出现快速进展（P〉0．05）。结论不同个体、不同程度其牙周病变的发展是不一样的，还不能认为IL-1RN（INTRON2）vNTR基因多态性会影响汉族人群慢性牙周炎的发展。     

牙周炎患者牙龈组织中IL-21表达的研究

目的：研究不同类型牙周炎患者牙龈组织中IL-21基因的表达,探讨其在牙周炎发病中的作用。方法：选择慢性牙周炎患者12例,侵袭性牙周炎8例,健康对照组8例,采用实时定量PCR方法定量检测IL-21 mRNA在牙龈组织表达情况。结果：慢性牙周炎、侵袭性牙周炎、健康对照组牙龈组织中均有IL-21 mRNA的表达,慢性牙周炎组和侵袭性牙周炎组IL-21 mRNA相对表达量分别为0.000534±0.000504和0.00602±0.000137,显著高于健康对照组0.000161±0.000352,差异有统计学意义(P<0.05)。慢性牙周炎和侵袭性牙周炎牙龈组织IL-21mRNA表达没有显著性差异（P>0.05）。结论：IL-21在慢性牙周炎发病机制中可能发挥重要作用。     

慢性牙周炎自然病程1 年观察及其与IL-1基因多态性的关系

目的:了解慢性牙周炎病程的自然发展及其与IL-1基因多态性的关系。方法:对166位慢性牙周炎患者进行为期1年的自然病程观察,分别在基线、12个月检查全口余留牙的牙周袋深度(PD)、临床附着丧失量(AL)、探诊出血(B0P),每个牙检查6个位点,对其中的111例牙周炎患者,分析其IL-1A-889、IL-1B 3954的基因多态性。结果:166人平均牙周袋深度增加1.12 mm,平均附着丧失量增加1.628 mm;有94位患者249个牙位出现了AL≥2 mm。没有发现IL-1A-889基因型分布及等位基因分布频率在快速进展组(至少1个部位AL增加≥2 mm)和非快速进展组间有显著性差异;IL-1B 3954基因型1/2的分布和等位基因2的频率在快速进展组高于非快速进展组(P<0.05)。1年后PD的改变和AL的改变在IL-1A-889和IL-1B 3954不同基因型携带者间无明显差异(P>0.05)。结论:不同个体其牙周病变的发展是不一样的;虽然IL-1B 3954等位基因2的频率在快速进展组高于非快速进展组,但分布频率很低,实际意义可能不大;没有发现PD和AL的改变与IL-1基因多态性有相关性。     

Interleukin-17 and interleukin-18 levels in saliva and plasma of patients with chronic periodontitis

Özçaka Ö, Nalbantsoy A, Buduneli N. Interleukin‐17 and interleukin‐18 levels in saliva and plasma of patients with chronic periodontitis. J Periodont Res 2011; 46: 592–598. © 2011 John Wiley & Sons A/S Background and Objective: This study was planned to investigate whether patients with chronic periodontitis exhibit different salivary and/or plasma concentrations of interleukin (IL)‐17 and IL‐18 compared with clinically healthy subjects. Material and Methods: Whole saliva and blood samples, together with full‐mouth clinical periodontal recordings, were obtained from 22 otherwise healthy untreated nonsmokers with chronic periodontitis and from 21 systemically and periodontally healthy control subjects. The concentrations of IL‐17 and IL‐18 in saliva and plasma were determined using ELISAs. Results: The healthy control group exhibited significantly lower values in all clinical periodontal measurements (p < 0.001). The salivary concentration of IL‐17 was significantly lower, and that of IL‐18 significantly higher, in patients from the chronic periodontitis group compared with healthy control subjects (p = 0.025 and p = 0.009, respectively). Plasma IL‐17 and IL‐18 concentrations were similar in the two study groups (p > 0.05). Conclusion: Within the limits of the present study, it may be suggested that an elevated salivary IL‐18 level in untreated nonsmoker chronic periodontitis patients has the potential to be a biomarker for periodontal tissue destruction.     

白细胞介素-21在不同牙周状态龈沟液中的表达及相关性分析

目的检测白细胞介素(Interleukin,IL)-21在不同牙周状态下龈沟液中的表达,探讨IL-21在牙周免疫中的可能作用。方法本研究共纳入47例患者,分为健康对照组(15例),轻度牙周炎组(10例),中重度牙周炎组(22例);记录患者一般信息、用Florida牙周探针检查牙周袋探诊深度(PD)和临床附着丧失(CAL)情况;收集牙周治疗前的龈沟液样本,采用酶联免疫吸附法(ELISA)测定不同牙周条件下龈沟液中IL-21的水平;并进行Pearson秩相关检验统计IL-21的表达与相关临床指标的关系。结果 3组龈沟液中IL-21平均浓度分别为(107.20±2.54)、(218.90±5.11)、(367.80±7.27)pg/m L,轻度牙周炎组及中重度牙周炎组龈沟液中IL-21水平显著高于对照组(P<0.05),其中以中、重度牙周炎组增高最为显著;中、重度牙周炎组龈沟液中IL-21水平分别与PD、CAL呈正相关关系(P<0.001)。结论 IL-21在牙周疾病中有较高的表达,尤其是以中重度牙周炎患者最为显著;由此推测IL-21在牙周疾病的发生发展中占有重要地位,与牙周组织的破坏有密切关系。     

Determination of NLRP3 (rs4612666) and IL-1B (rs1143634) genetic polymorphisms in periodontally diseased and healthy subjects

ObjectiveThe focus of the current study was to identify if a possible association between NLRP3 (rs4612666) and IL-1B (rs1143634) single-nucleotide polymorphisms (SNPs) may be implicated in the etiopathogenesis of chronic periodontitis (CP) in a Colombian population.DesignOne hundred and twenty-four CP subjects and 81 periodontally healthy controls (HC) were recruited. Periodontal status was assessed by criteria based on probing depth, clinical attachment level, extent, and severity of periodontal breakdown. Human genomic DNA was obtained from saliva samples of the study subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the NLRP3 (rs4612666) and IL-1B (rs1143634) SNPs. The association of polymorphisms with CP was assessed individually and adjusted for confounding using a multivariate binary logistic regression model.ResultsBivariate analysis showed a weak association between CT genotype of NLRP3 (rs4612666) SNP and CP, however after logistic regression analysis, neither NLRP3 (rs4612666) nor IL-1B (rs1143634) polymorphisms were strongly/independently associated with disease status. Even so, an interaction effect was significantly detected not only among CT/CC genotypes of NLRP3 gene regarding to the age stratum ≥48 years, but also between CC genotype of the same gene and smoking habit.ConclusionAlthough the present results do not support that IL-1B (rs1143634) SNP could be identified as a risk predictor for CP in the present population, the synergistic interaction of the CT/CC genotypes of NLRP3 (rs4612666) SNP with ageing and/or smoking habit potentially might play a significant role in the pathogenic pathways of periodontal disease.     

IL-1α刺激人牙龈成纤维细胞产生IL-11和IL-6的比较研究

目的比较IL—1α刺激牙龈成纤维细胞（human gingival fibroblast，HGF）IL-11和IL-6的表达和调控。方法收集细胞上清液，ELISA法测定IL-11／IL-6的水平；提取细胞mRNA，实时定量RT—PCR法分析IL-11mRNA的表达。结果IL-1α显著增加HGFIL-11／IL-6的表达（P〈0．05），其中IL-6水平增加最为显著；HGF受到IL—1α刺激IL-11mRNA表达明显增强。吲哚关欣在蛋白质（P〈0．05）和mRNA水平都显著抑制了IL—1α刺激的HGFIL-11的产生，但对IL-6的产生在蛋白质水平则有不同影响，五株HGF细胞系中有四株IL-6的产生受到显著抑制（P〈0．05），另一株则表现为轻微促进IL-6的产生。IL-1α刺激IL-11的产生也都受到staurosporine的抑制（P〈0．05），而IL-6的产生在细胞株HGF-2受到显著抑制（P〈0．05），在HGF-3株则不受影响。结论IL-1α刺激HGF显著增加IL-11／IL-6的产生，IL-11与IL-6在该刺激产生过程中受内源性前列腺素及蛋白激酶C信号途径调控的机理不完全相同。     

新疆木垒县哈萨克族慢性牙周炎患者血清与唾液中IL-6、IL-17的表达及相关性分析

目的:研究哈萨克族慢性牙周炎(chronic periodontitis,CP)患者血清和唾液中白细胞介素17(interleukin 17, IL17 )、白细胞介素6(interleukin 6, IL6 ) 的活性表达及相关性分析。方法:选择哈萨克族慢性牙周炎患者192例,健康人100例,记录临床牙周检查指标,采集非刺激性全唾液及外周血液各5 mL。采用抗体夹心ELISA法测定CP患者与健康人群唾液及血液中IL-17、IL-6总量和浓度。结果:牙周炎患者的唾液IL-6、IL-17浓度要显著高于血清IL-6、IL-17。在唾液中IL-6与IL-17彼此呈中度正相关性,且二者与牙周临床指标均为高度正相关关系。结论:唾液IL-6、IL-17在哈萨克族慢性牙周炎患者的表达水平明显增高,且与病情严重程度相关,可作为萨克族慢性牙周炎患者的诊断标志物,对二者的相关性可从基因学方面进行下一步研究。     

Effect of periodontal treatment on IL-1beta, IL-1ra, and IL-10 levels in gingival crevicular fluid in patients with aggressive periodontitis

Aim: The aim of this study was to examine the effect of phase I periodontal treatment on the levels of interleukin (IL)‐1β, IL‐1ra, and IL‐10 in gingival crevicular fluid (GCF) in patients with generalized aggressive periodontitis (G‐AgP). Material and Methods: Data were obtained from 15 patients with aggressive periodontitis and 15 healthy controls. GCF was collected from at least four pre‐selected sites (one shallow, at least two moderate, or at least one deep pockets) in patients with G‐AgP. In the healthy group, GCF samples were collected from one site. The cytokine levels were determined by an enzyme‐linked immunosorbent assay. Probing depth, clinical attachment level (CAL), gingival and plaque indices, and bleeding on probing were measured. The GCF sampling and clinical measurements were recorded at baseline and 6 weeks later after periodontal treatment. Results: IL‐1β levels were significantly higher at the moderate and deep pocket sites compared with the shallow sites (p<0.05). After periodontal therapy, IL‐1β levels were significantly reduced in the moderate and deep pocket sites (p<0.05). IL‐1ra levels at baseline of the moderate and deep pocket sites were significantly lower than the control sites (p<0.05). IL‐10 levels were similar in all pockets and did not change after periodontal therapy. Conclusions: The periodontal treatment improves the clinical parameters in G‐AgP, and this improvement is evident in deep pocket sites for pocket depth and CAL values. These results confirm that IL‐1β is effective for evaluating the periodontal inflammation and can thus be used as a laboratory tool for assessing the activity of periodontal disease.     

Investigation of the interleukin-1 gene cluster polymorphisms in Jordanian patients with chronic and aggressive periodontitis

Objective

Interleukin-1 (IL-1) is a proinflammatory cytokine that is highly elevated in response to bacterial biofilms and is a potential risk factor for periodontal diseases. IL-1 gene polymorphisms have been associated with the IL-1 level. The aim of this study was to investigate if IL-1 gene cluster polymorphisms are associated with chronic (CP) and aggressive (AgP) periodontitis in a Jordanian population.

Methods

A total of 100 CP, 80 AgP patients and 80 controls were genotyped using PCR for IL-1RN-86-bp VNTR and PCR-RFLP for IL-1A-889, IL-1B-511, -35, +3953, and IL-1RN +8006, +9589, +11100 SNPs. The distribution of alleles and genotypes between groups was compared using χ² analysis. Estimation of haplotype frequencies was carried out using the EH programme.

Results

The IL-1RN8006 SNP and the IL-1RN-VNTR were associated with CP but not with AgP. The C allele and TC genotype of IL-1RN8006 were increased in CP (P_corr = 0.002, 0.00026 respectively). The A1 allele and A1/A1 genotype of the IL1-RN-VNTR were significantly increased in CP (P_corr = 0.0007, <0.0001 respectively). The CA1 haplotype formed by both markers was present in 29 CP patients but not in any of the controls (P < 0.0001). No significant differences were found in the distribution of allele and genotype frequencies of the other markers between CP and AgP cases and controls.

Conclusions

IL-1RN 8006 and IL-1RN VNTR were associated with CP but not AgP in a Jordanian population, whilst other investigated markers in IL-1A, IL-1B and IL-1RN were not associated with either CP or AgP.