IL-1β In Gingival Crevicular Fluid Research Articles

Effects of Periodontal Therapy During Pregnancy on Periodontal Status, Biologic Parameters, and Pregnancy Outcomes: A Pilot Study

Few studies have examined the potential effects of periodontal treatment during pregnancy on pregnancy outcomes, periodontal status, and inflammatory biomarkers. A randomized, delayed-treatment, controlled pilot trial was conducted to evaluate the effects of second-trimester scaling and root planing and the use of a sonic toothbrush on the rate of preterm delivery (<37 weeks gestation). Secondary outcome measures included changes in periodontal status, levels of eight oral pathogens, levels of gingival crevicular fluid (GCF) interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)), 8-isoprostane (8-iso), and IL-6, and serum levels of IL-6, soluble intercellular adhesion molecule 1 (sICAM1), 8-isoprostane, soluble glycoprotein 130 (sGP130), IL-6 soluble receptor (IL-6sr), and C-reactive protein (CRP). Logistic regression models were used to test for effects of treatment on preterm delivery. Secondary outcomes were analyzed by analysis of covariance adjusting for subject baseline values. Periodontal intervention resulted in a significantly decreased incidence odds ratio (OR) for preterm delivery (OR = 0.26; 95% confidence interval = 0.08 to 0.85), adjusting for baseline periodontal status which was unbalanced after randomization. Pregnancy without periodontal treatment was associated with significant increases in probing depths, plaque scores, GCF IL-1beta, and GCF IL-6 levels. Intervention resulted in significant improvements in clinical status (attachment level, probing depth, plaque, gingivitis, and bleeding on probing scores) and significant decreases in levels of Prevotella nigrescens and Prevotella intermedia, serum IL-6sr, and GCF IL-1beta. Results from this pilot study (67 subjects) provide further evidence supporting the potential benefits of periodontal treatment on pregnancy outcomes. Treatment was safe, improved periodontal health, and prevented periodontal disease progression. Preliminary data show a 3.8-fold reduction in the rate of preterm delivery, a decrease in periodontal pathogen load, and a decrease in both GCF IL-1beta and serum markers of IL-6 response. However, further studies will be needed to substantiate these early findings.

Changes in Periodontal and Rheumatological Conditions After 2 Years in Patients With Juvenile Idiopathic Arthritis

The aim of this study was to monitor changes in periodontal inflammation in patients with juvenile idiopathic arthritis (JIA) for 2 years. We investigated the influence of rheumatic disease activity and antirheumatic medication on clinical and immunological parameters of periodontal inflammation in these individuals. Two years after a baseline examination, the periodontal and rheumatological conditions of 18 adolescents with JIA and 14 control subjects were described. The clinical periodontal inflammation was monitored by registration of visual plaque, marginal bleeding, probing depth, and clinical attachment loss (AL). Periodontal inflammation was also assessed by analysis of the cytokines interleukin (IL)-1beta and IL-18 and the collagenase matrix metalloproteinase (MMP)-8 by enzyme-linked immunosorbent assay. The erythrocyte sedimentation rate and clinical rheumatological parameters were significantly improved at the 2-year follow-up. The number of sites with plaque decreased, and the number of pockets >/=4 mm increased, whereas bleeding levels and the extension of AL remained unchanged. IL-1beta in gingival crevicular fluid decreased significantly in the JIA group after 2 years. No differences were observed for IL-1beta, MMP-8, or IL-18 levels between groups after 2 years. Two years after the baseline examination, no clinical or laboratory differences in periodontal inflammation could be found between JIA patients and control subjects.

Pain Discomfort and Crevicular Fluid Changes Induced by Orthodontic Elastic Separators in Children

The objective of the present investigation was to study the experience of pain after placement of orthodontic elastic separators and the possible associations with the gingival crevicular fluid (GCF) composition changes at the level of interleukin 1-beta (IL-1β), substance P (SP), and prostaglandin-E 2 (PGE 2). Eighteen children (mean age 10.8 yrs) in the beginning of the orthodontic treatment were included. Molar elastic separators were inserted mesially to 2 first upper or lower molars. One of the antagonist molars served as control. The GCF was collected from the distobuccal and distopalatal sites from each molar, before (day −7, day 0) and after the placement of separators (1 h, day 1, and day 7). Pain intensity was recorded using a visual analog scale (VAS). The contents of IL-1β, SP, and PGE 2 were determined by enzyme-linked immunosorbent assay. Pain intensity increased after 1 h (VAS = 11) and remained high on day 1 (VAS = 13). On day 7, no significant pain was reported. After 1 h, 1 day, and 7 days, mean GCF IL-1β levels were significantly elevated at treatment teeth compared to control teeth (highest day 1). The GCF levels of SP and PGE 2 for the treatment teeth were significantly higher at day 1 and day 7 than the control teeth. All 3 mediators remained at baseline levels throughout the experiment for the control teeth. The intensity of pain at 1 h was associated to PGE 2 levels (R 2 = 0.38; P < .05), whereas at day 1, the intensity of pain was associated to IL-1β levels (R 2 = 0.63, P < .0001). Thus, we report a rapid release of biochemical markers (1 h) that peaked after 1 day and partially decreased 7 days later. The intensity of pain followed a similar pattern. Associations were found between the experience of pain intensity and the GCF mediator levels. Perspective The study may help to detect, in an initial stage, individuals prone to perceive higher level of pain during orthodontic treatment. This may help in the development of methods that will better control and/or alleviate the discomfort of pain during tooth movement.

Inflammatory mediators and periodontitis in patients with asymptomatic third molars

Purpose: Our goal was to report the detection and levels of gingival crevicular fluid (GCF) inflammatory mediators, sampled at the mesial of 4 first molars and distal of 4 second molars, in 316 patients with asymptomatic third molars. Patients and Methods: Levels of GCF inflammatory mediators, interleukin (IL)-1β and prostaglandin (PG)E2, were determined and log transformed for each patient. Z scores were calculated using the mean and standard deviation of the log values for the entire sample of 316 patients. The log mediator levels and Z scores of patients who had probing depths (PDs) less than 5 mm (n = 238) were compared with patients with at least 1 PD equal to or greater than 5 mm (n = 78) on the distal of second molars or around third molars. A periodontal Composite GCF Inflammation Score was calculated for each patient by summing the Z scores obtained for IL-1β and PGE2 for that patient. Results: The levels of GCF IL-1β and PGE2 were higher if a patient had a PD equal to or greater than 5 mm in the third molar region. The Composite GCF Inflammation Score indicated “elevated inflammation” if a PD equal to or greater than 5 mm was found in the third molar region as well. Conclusions: These data suggest that asymptomatic patients with PD equal to or greater than 5 mm in the third molar region with associated periodontal attachment loss have increased levels of biochemical mediators of inflammation compared with patients with PD less than 5 mm. These findings are consistent with the concept that early periodontitis in young adults that initiates in the third molar region is associated with increases in key inflammatory mediators. © 2002 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 60:1241-1245, 2002

Increased interleukin-1beta concentration in gingival crevicular fluid as a characteristic of periodontitis.

The levels of interleukin-1beta (IL-1beta) have been reported to be higher in sites with periodontitis than in healthy controls. This may be the result of a more severe inflammation and/or constitutional differences in IL-1beta production. Our aim was to test the hypothesis that the level of IL-1beta in gingival crevicular fluid (GCF) is a characteristic trait of periodontitis, regardless of the degree of tissue destruction. As a secondary aim, we investigated the correlation between IL-1beta and neutrophil elastase. An untreated population was used. GCF samples from inflamed sites in 13 patients with gingivitis (GG), and from inflamed sites with shallow (GP) and deep (PP) pockets in 18 patients with periodontitis were collected. Interleukin-1beta, elastase-alpha-1-antitrypsin complex (E-A1AT), alpha-1-antitrypsin (A1AT), and alpha-2-macroglobulin (A2MG) were measured with ELISA. Elastase activity was measured with a specific substrate. The concentration of IL-1beta was significantly higher in PP than in GG, but no significant differences were detected between PP and GP. A weak positive correlation between the elastase activity and IL-1beta was also observed. The elastase activity had a tendency to be higher in PP, although no significant difference was found among the 3 groups. The concentrations of E-A1AT, A1AT, and A2MG were similar in the 3 types of sites. The levels of IL-1beta in GCF were increased in samples from periodontitis patients, regardless of the severity of disease at the sampled site, suggesting that the levels of IL-1beta are typical of a given patient.

Heightened gingival inflammation and attachment loss in type 2 diabetics with hyperlipidemia.

Our previous studies in diabetic (DB) rats suggest that hyperlipidemia may cause a dysregulation of the cellular and local cytokine response to periodontitis (AP). The objective of the present study was to determine if diabetes has a similar dysregulatory effect on the gingival response to AP in humans. Peripheral blood, as well as gingival tissue (GT) and gingival crevicular fluid (GCF), was obtained from a total of 35 patients who were categorized into the following groups based on level of diabetic (type 2) control and presence or absence of adult periodontitis (AP): group 1, systemically and periodontally healthy (n = 6); group 2, systemically healthy with adult periodontitis (n = 7); group 3, well-controlled diabetes and periodontally healthy (n = 6); group 4, well-controlled diabetes with adult periodontitis (n = 5); group 5, poorly controlled diabetes and periodontally healthy (n = 5); group 6, poorly controlled diabetes and adult periodontitis (n = 6). All subjects were given a thorough periodontal examination, including probing depths (PD), clinical attachment levels (CAL), gingival index (GI), plaque index (PI), and vertical bitewing radiographs. Blood studies included levels of glycated hemoglobin (HbA1c), triglycerides (TG), cholesterol (CHL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). The levels of interleukin-1 beta (IL-1beta) in GCF and GT, interleukin-6 (IL-6), and platelet-derived growth factor AB (PDGF-AB) in GT from patients in each experimental group were analyzed by enzyme-linked immunosorbent assay (ELISA). Our results indicate that all clinical indices except PI were significantly elevated in the poorly controlled and well-controlled diabetics, compared to systemically healthy patients, but only in the subjects without preexisiting AP (Tukey's multiple comparisons, P <0.05). Pairwise linear regression analysis revealed significant (P <0.01) positive associations between periodontal inflammation (PD, CAL, PI, GI) and levels of GCF IL-1beta, GT IL- 1beta GT IL-6, but not GT PDGF; moreover, GT IL-6 levels were significantly associated (P<0.05) with GT IL-1beta. As TG levels increased in the non-AP patients (group 1 < group 3 < group 5), there was a trend, not significant, for increased GCF IL-1beta levels and increased gingival inflammation. Interestingly, periodontitis resulted in increased PDGF-AB levels in the gingiva of systemically healthy and well-controlled diabetes patients, but this increase was obtunded in poorly controlled diabetes patients. This confirms our earlier work in the diabetic rat model. These studies indicate that decreased metabolic control in type 2 diabetics results in increased serum triglycerides and has a negative influence on all clinical measures of periodontal health, particularly in patients without preexisting periodontitis. Levels of the cytokine IL- 1beta showed a trend for increasing as diabetic control diminished. In contrast, levels of the growth factor PDGF, which normally increase in periodontitis, decreased in poorly controlled diabetics with periodontitis. These studies suggest a possible dysregulation of the normal cytokine/growth factor signaling axis in poorly controlled type 2 diabetics that may contribute to periodontal breakdown/diminished repair.

Effect of an antibacterial dental varnish on the levels of prostanoids, leukotriene B4, and interleukin-1β in gingival crevicular fluid

The aim of this study was to investigate the effects of a chlorhexidine/thymol-containing dental varnish on the levels of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2), leukotriene B4 (LTB4), and interleukin-1β (IL-1β) in gingival crevicular fluid (GCF). The material consisted of 15 adolescents undergoing treatment with fixed orthodontic appliances. Four buccal sites adjacent to bands or brackets and exhibiting a mild chronic gingival inflammation were selected in the upper quadrants of each patient. According to a splitmouth technique, the first and second quadrants were randomly treated with either a varnish (Cervitec®) containing 1% chlorhexidine diacetate and thymol (CHX/thymol) or a placebo varnish without active ingredients. The varnishes were applied immediately after the baseline registration, and follow-up examinations were carried out after 3, 8, and 30 days. GCF was sampled with the aid of a paper strip and the volume was determined using a Periotron® 8000. The concentrations of PGE2, PGI2, LTB4, and IL-1β in GCF were assessed using radioimmunoassay and ELISA techniques. The results unveiled statistically significant reductions of PGE2, PGI2, and LTB4 levels in GCF following the active varnish treatment when compared to baseline values. A slight drop in IL-1β levels was registered after both active and placebo varnish applications, but the differences were not significant. The results suggest that treatment with an antibacterial varnish decreases the levels of inflammatory mediators PGE2, PGI2, and LTB4 in gingival crevicular fluid and further support the concept that topical application of a CHX/thymol-containing varnish is beneficial in patients with chronic gingival inflammation.

New concepts regarding the pathogenesis of periodontal disease in HIV infection.

Periodontal manifestations of human immunodeficiency virus (HIV) infection were first described in 1987. Initially, the lesions receiving attention were HIV-associated gingivitis (now known as linear gingival erythema [LGE]) and HIV-associated periodontitis (now known as necrotizing ulcerative periodontitis [NUP]). The true prevalence of LGE was difficult to determine due to variable diagnostic criteria. Recently, LGE has been associated with intraoral Candida infection. The prevalence of NUP is low (< or = 5%), and this lesion is associated with pronounced immunosuppression. Current focus on the periodontal manifestations of HIV infection centers on rapid progression of chronic adult periodontitis in HIV+ patients. Attempts to identify the pathogenesis of the increased progression of periodontitis have not proven successful. For example, analysis of subgingival plaque for the presence of bacterial pathogens has failed to detect differences between HIV+ and HIV- patients. Recently our laboratory has identified alterations in the host response in the gingival crevice of HIV+ patients. Comparing HIV+ and HIV- injecting drug users (IDU), levels of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) in gingival crevicular fluid (GCF) were slightly elevated at sites with a probing depth of 1 to 3 mm. At deeper sites (> or = 4 mm), total IL-1 beta in GCF was significantly greater in HIV+ individuals. Using the lysosomal acid glycohydrolase beta-glucuronidase (beta G) as a measure of the influx of polymorphonuclear leukocytes (PMN) into the gingival crevice, our data indicated a significant correlation of total beta G in GCF and probing depth in the HIV-IDU (r = 76; P = .02). This result was similar to what we have observed in other studies. In contrast, for HIV+ subjects, total beta G was not associated with probing depth (r = .20; NS). These data suggest that HIV+ patients have altered regulation of PMN recruitment into the gingival crevice. We have begun to investigate the conditions under which subgingival Candida may contribute total periodontal lesions in HIV+ individuals. Candida from subgingival sites has been cultured in HIV+ individuals. Subgingival Candida was distinct from Candida isolated from tongue and buccal mucosal surfaces (as indicated by genomic fingerprinting). We hypothesize the absence of adequate priming of PMN by HIV+ patients. This may be due to a reduced Th1 lymphocyte response. The inability of HIV+ individuals to adequately prime PMN may allow Candida to colonize the subgingival environment. In that milieu, it may act directly or in concert with subgingival bacterial pathogens, or as a cofactor (by inducing production of proinflammatory cytokines) to increase the occurrence of periodontal attachment loss.

Relationships between clinical parameters, interleukin 1B and histopathologic findings of gingival tissue in periodontitis patients

IL-1β is one of the cytokines which can induce bone resorption and connective tissue destruction. Previous studies demonstrated that the amount of IL-1β in gingival crevicular fluid (GCF) was closely related to the severity of gingival index (GI) and probing depth (PD). To further investigate whether the amount of IL-1β in GCF and the tissues adjacent to the periodontal pockets can reflect the degree of inflammation and destruction of these tissues, the GCF and inflamed gingival specimens were harvested from 14 periodontal patients and IL-1β in these samples was measured by ELISA. Clinical parameters of the sampled teeth were also recorded. Possible relations among periodontal parameters, GCF or tissue IL-1β and the degrees of inflammation in tissue sections were analysed statistically. The results showed that with increasing GI and PD, there was an elevation of GCF and tissue IL-1β activity. GCF flow also showed a tendency to increase with a higher percentage of inflammatory infiltrate. The GCF and tissue IL-1β activity were significantly correlated with clinical parameters (GI, PD and GCF flow), as well as with the percentage of inflammatory infiltrate and tissue alterations. With the exception of a significantly negative correlation with the extent of inflammation, no obvious relation between the GCF or tissue concentration of IL-1β and the state of tissue pathology could be detected. In conclusion, measurements of IL-1β activity in GCF or diseased tissues based on the classification of clinical parameters can reflect the degree of inflammation within periodontal disease tissue. These observations indicate that clinical parameters can provide reliable means for evaluation of the severity of periodontal disease, and that IL-1β plays a pivotal role in the pathogenic mechanism of periodontal tissue destruction.

Interleukin-1 beta concentration of gingival crevicular fluid.

The concentration of interleukin-1 beta is elevated in inflamed gingival tissue. Therefore a method for the measurement of interleukin-1 beta (Il-1 beta) in gingival crevicular fluid (GCF) using a commercially available Il-1 beta ELISA was developed. GCF was collected with periopaper strips and 4 protocols of sampling using filter paper strips were tested; the method with a recovery rate of 111.9% (SD: +/- 14.5%) was chosen for subsequent analysis of all samples. Il-1 beta concentration in GCF of periodontitis patients and a healthy control group was determined. Patients (n = 19, mean age: 29.3 years) had not been treated. The healthy control group (n = 14, mean age: 22.8 years) showed, after a hygiene regimen of 2 weeks, no clinical signs of gingival/periodontal inflammation. Probing depth, clinical attachment level, bleeding upon probing, and a modified plaque index were recorded. Il-1 beta could be detected in all GCF samples. The concentration ranged between 22.8 ng/ml and 150 ng/ml in the healthy control group and between 85.8 ng/ml and 882.2 ng/ml in the periodontitis patients. No sex-related differences were noted. According to our present results the determination of GCF Il-1 beta concentration is possible using commercially available test kits if the principle of sample preparation is adapted to the specific requirements of GCF analysis.