Activation of interleukin 1beta gene transcription by human cytomegalovirus: molecular mechanisms and relevance to periodontitis

In recent years, studies have demonstrated an association between human cytomegalovirus (HCMV) and destructive periodontal disease. It has been shown that reactivation of HCMV in periodontitis lesions may be related to progressing periodontal disease. Several possible mechanisms by which HCMV exerts periodontopathic potential have been previously proposed. These are reviewed and include the upregulation of bone resorptive cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) by active HCMV infection at the periodontitis site. This review focuses on the molecular basis of IL-1beta gene activation by HCMV immediate early (IE) gene products. A novel hypothesis is also described whereby HCMV plays a significant role in the pathogenesis of periodontal disease by the ability of its IE proteins to strongly transactivate IL-1beta gene expression. More studies are needed to further explore this hypothesis and clarify the association between HCMV and periodontitis.     

Salivary interleukin-1β levels in patients with chronic periodontitis before and after periodontal phase I therapy and healthy controls: a case-control study

Background: The role of interleukin (IL)‐1β in periodontal disease pathogenesis is well researched. This study aimed to assess and compare the salivary IL‐1β levels in patients with chronic periodontitis before and after periodontal phase I therapy and periodontally healthy controls. Further, relationships between IL‐1β levels and various clinical parameters were explored. Methods: Twenty‐eight patients with moderate‐to‐severe generalized chronic periodontitis and 24 age‐, race‐, and ethnicity‐matched controls participated in this study. Saliva samples were obtained from all patients. The clinical parameters recorded were clinical attachment loss (AL), probing depth, bleeding on probing, periodontal index, and gingival index. Clinical evaluation and sample collection were repeated 1 month after periodontal phase I therapy in patients with periodontitis. IL‐1β levels were assessed using enzyme‐linked immunosorbent assay. Results: Mean IL‐1β levels in patients with periodontitis at baseline (1,312.75 pg/mL) were significantly higher (P <0.0001; eight‐fold) than in controls (161.51 pg/mL). Although treatment in patients with periodontitis resulted in significant reduction in IL‐1β levels (mean: 674.34 pg/mL; P = 0.001), they remained significantly higher (P <0.0001; four‐fold) than control levels. There were significant correlations between IL‐1β levels and all clinical parameters (P <0.01) except percentage sites with clinical AL >2 mm (P >0.05). Conclusions: The data indicate that IL‐1β levels are raised in the saliva of patients with chronic periodontitis, which are reduced after phase I therapy, suggesting a close association between salivary IL‐1β and periodontitis. Additional longitudinal studies are needed to validate salivary IL‐1β as a marker for periodontal disease.     

Interleukin‐1 Gene Polymorphisms and Chronic Periodontitis in Adult Whites: A Systematic Review and Meta‐Analysis

Background: Interleukin‐1 (IL‐1) gene polymorphisms have been associated with increased levels of inflammatory mediators and several inflammatory diseases. Periodontitis is a bacterially induced chronic inflammatory disease that destroys the connective tissues and bone that support the teeth, affects substantial numbers of adults, and has been implicated as a contributing factor in systemic diseases. IL‐1 gene polymorphisms, most prominently IL1A (?889), IL1A (+4845), and IL1B (+3954), have been associated with chronic periodontitis (CP) in whites. Since the first report, ≥125 studies have examined IL‐1 gene variation in relation to periodontal disease. These studies have produced mixed findings in diverse periodontal phenotypes and in different ethnic groups. One previous meta‐analysis has been published on this topic and supported an association between IL‐1 genes and periodontitis, but considerable doubt remains about the patient populations in which the association may be of clinical relevance. Methods: A systematic review and meta‐analysis was conducted in an attempt to clarify whether IL‐1 gene variants were associated with well‐defined clinical phenotypes of CP in white patients. Study inclusion criteria focused on the analytic framework originally proposed for the IL‐1 genetic effect in which overexpression of inflammatory mediators is hypothesized to result in more severe periodontitis in response to a bacterial challenge. Results: Twenty‐seven studies were included in the qualitative analysis. Nineteen studies yielded significant associations between carriage of the minor IL‐1 alleles and periodontitis. The meta‐analysis, based on 13 qualifying studies, found significant effects for the two individual gene variations (IL1A odds ratio [OR] = 1.48; IL1B OR = 1.54) and for a composite genotype that combines minor alleles at each locus (OR = 1.51). Statistically significant heterogeneity was found that could not be explained, but there was no indication of publication bias. Conclusion: This review and meta‐analysis show that IL1A and IL1B genetic variations are significant contributors to CP in whites.     

Viruses in periodontal disease - a review

The purpose of this review was to evaluate the evidence supporting the hypothesis that viral infection plays a role in the development of periodontitis. An involvement in periodontal diseases has been suspected specifically for human immunodeficiency virus (HIV) and herpes viruses. An association has been demonstrated between HIV infection and some distinct forms of periodontal infection, i.e. necrotizing lesions. Furthermore, reports of increased prevalence and severity of chronic periodontitis in HIV-positive subjects suggests that HIV infection predispose to chronic periodontitis. Several studies, most of them from the same research group, have demonstrated an association of herpesviruses with periodontal disease. Viral DNA have been detected in gingival tissue, gingival cervicular fluid (GCF) and subgingival plaque from periodontaly diseased sites. In addition markers of herpesviral activation have been demonstrated in the GCF from periodontal lesions. Active human cytomegalovirus (HCMV) replication in periodontal sites may suggest that HCMV re-activation triggers periodontal disease activity. Concerns regarding sampling, methods and interpretation cast doubts on the role of viruses as causes of periodontal disease.     

Salivary Levels of NLRP3 Inflammasome‐Related Proteins as Potential Biomarkers of Periodontal Clinical Status

Background: Emerging evidence suggests that activation of inflammasomes plays a central mechanism in pathogenesis of periodontitis. This study aims to compare salivary levels of nod‐like receptor family pyrin domain containing protein (NLRP) 3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC), cysteine aspartase (caspase)‐1, and interleukin (IL)‐1β from individuals with aggressive (AgP) or chronic periodontitis (CP) and healthy controls (HC), as well as elucidate its association with periodontal clinical status. Methods: Saliva samples from individuals with CP (n = 75), AgP (n = 20), and HC (n = 69) were collected. Periodontal status was assessed by measurement of probing depth, clinical attachment level, and extent and severity of disease. Salivary levels of analytes were analyzed by enzyme‐linked immunosorbent assay. Association between biomarkers with CP or AgP was analyzed using multivariate binary logistic regression models. Results: Significantly higher levels of NLRP3, ASC, and IL‐1β were detected in periodontitis groups in comparison to the periodontally HC group. However, no significant differences were observed for caspase‐1 levels between clinical groups, and only NLRP3 salivary concentration was significantly higher in AgP compared with CP patients. Also, positive significant correlations among NLRP3, ASC, and IL‐1β salivary concentrations and clinical parameters were observed. Logistic regression analyses revealed a strong/independent association of NLRP3, ASC, and IL‐1β salivary levels with CP and AgP. Conclusion: Although the concentration of caspase‐1 in saliva samples makes its determination useless for detection of periodontal disease and/or its severity, salivary levels of NLRP3, ASC, and IL‐1β may act as strong/independent indicators of amount and extent of periodontal breakdown in both CP and AgP and could potentially be used for prevention and therapy of this group of diseases.     

Salivary Concentrations of Interleukin (IL)‐1β, IL‐17A,and IL‐23 Vary in Relation to Periodontal Status

Background: Interleukin (IL)‐23‐induced T helper (Th) 17 pathway is involved in the pathogenesis of periodontal disease. This study’s aim is to determine levels of IL‐1β, IL‐17A, IL‐23, and lipopolysaccharide (LPS) in saliva, and to examine whether their salivary concentrations are associated with periodontal health status. Methods: Saliva samples originated from 220 participants; 76 had generalized periodontitis (GP) and 65 had localized periodontitis (LP), whereas 79 without periodontitis were used as controls. Cytokine analyses were performed by a flow cytometry–based technique and LPS analyses from pellet by commercially optimized assay coupled with chromogenic substrate. Results: Salivary concentrations of IL‐17A and IL‐23 were elevated significantly in patients with LP compared with controls and patients with GP. Salivary IL‐1β concentrations were significantly higher in patients with GP than in patients with LP, whereas no difference was found between LP and control groups. Significant correlation was found between concentrations of IL‐17A and IL‐23 or IL‐1β. LPS concentrations did not have significant associations with any of the tested ILs. Conclusion: Elevated salivary IL‐1β concentrations are related to GP, whereas distinct elevation and reduction profiles of IL‐17A and IL‐23 are detected in saliva of patients with LP and GP.     

Historical aspects of studies on roles of the inflammasome in the pathogenesis of periodontal diseases

The proinflammatory cytokine interleukin‐1β (IL‐1β) is produced as inactive proIL‐1β and then processed by caspase‐1 to become active. In 2002, it was demonstrated that the intracellular multiprotein complex known as the inflammasome functions as a molecular platform to trigger activation of caspase‐1. Inflammasomes are known to function as intracellular sensors for a broad spectrum of various pathogen‐associated and damage‐associated molecular patterns. In 1985, it was demonstrated that Porphyromonas gingivalis, a representative bacterium causing chronic periodontitis, induces IL‐1 production by murine peritoneal macrophages. Since then, many studies have suggested that IL‐1, particularly IL‐1β plays key roles in the pathogenesis of periodontal diseases. However, the term “inflammasome” was not used until the involvement of inflammasomes in periodontal disease was suggested in 2009. Several subsequent studies on the roles of the inflammasome in the pathogenesis of periodontal diseases have been published. Interestingly, two contradictory reports on the modulation of inflammasomes by P. gingivalis have been published. Some papers have described how P. gingivalis activates the inflammasome to produce IL‐1β whereas some stated that P. gingivalis inhibits inflammasome activation to subvert immune responses. Several lines of evidence have suggested that the inflammasome activation is modulated by periodontopathic bacteria other than P. gingivalis. Hence, studies on the roles of inflammasomes in the pathogenesis of periodontal diseases began only 8 years ago and many pathological roles of inflammasomes remain to be clarified.     

Association Between Periodontitis and Amyloid β Peptide in Elderly People With and Without Cognitive Impairment

Background: Evidence that periodontal disease is a possible risk factor for cognitive impairment may be explained by the inflammatory hypothesis. The aim of this study is to determine whether periodontitis is related to the amyloid β (Aβ) load in blood and the role of any such relationship in the association between Aβ and cognitive impairment. Methods: A case‐control study was performed in elderly people diagnosed with cognitive impairment with or without dementia (cases group) and cognitively healthy elderly people (control group); data were collected on the medical and dental history of participants, and blood samples were drawn to determine Aβ levels using enzyme‐linked immunosorbent assay. Results: The study included 166 patients and 122 control participants. Higher blood Aβ_1‐42 levels (P = 0.01) and higher Aβ_42:40 ratio (P = 0.06) were observed in participants with severe attachment loss than in other participants. Periodontitis was a significant interaction variable, given that the association between Aβ_1‐42 and Aβ_1‐40 and cognitive impairment was only observed in patients with severe periodontitis. According to these data, periodontitis may be a modulating variable of the association between Aβ and cognitive impairment. Conclusions: Plasma Aβ_1‐42 levels are higher in individuals who have severe periodontal disease. The presence of periodontitis may modify the association between Aβ and cognitive impairment.     

Does Obstructive Sleep Apnea Increase the Risk for Periodontal Disease? A Case‐Control Study

Background: A possible association between periodontitis and obstructive sleep apnea (OSA) has been suggested. The aim of this study is to compare periodontitis prevalence between controls and patients with OSA by assessing clinical periodontal parameters and gingival crevicular fluid (GCF) levels of interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, and high‐sensitive C‐reactive protein (hs‐CRP); serum hs‐CRP was also sampled. Methods: A case‐control study was performed that included 163 individuals: 83 individuals (18 females and 65 males) with OSA and 80 non‐OSA individuals (23 females and 57 males) as controls. The test group was classified according to OSA severity. Clinical periodontal measurements were recorded, and GCF samples were collected. GCF hs‐CRP, IL‐lβ, and TNF‐α levels were analyzed using an enzyme‐linked immunosorbent assay method. Serum hs‐CRP was measured by latex‐enhanced immunoturbidimetric assay. Results: Prevalence of periodontitis in the OSA group (96.4%) was significantly higher than in the control group (75% [P <0.001]). Severe periodontitis prevalence was higher in the OSA group than control group. All periodontal clinical parameters and GCF IL‐lβ concentrations were significantly higher in patients with OSA than in controls (P = 0.001). No significant differences were found between the mild OSA and moderate‐to‐severe OSA groups. Additionally, there was no significant difference in GCF TNF‐α and hs‐CRP levels between the groups (P >0.05). Serum hs‐CRP levels were significantly higher in patients with OSA. A significant correlation was found between GCF IL‐1β and all clinical parameters. Conclusions: Results demonstrated higher prevalence of periodontitis and higher levels of GCF IL‐1β and serum hs‐CRP in patients with OSA. However, there is still a need for randomized clinical trials testing oral care interventions.     

Alarm anti‐protease trappin‐2 negatively correlates with proinflammatory cytokines in patients with periodontitis

1 Background

Trappin‐2 is a potent biologically active serine protease inhibitor with anti‐inflammatory properties that has also been characterized as an “alarm anti‐protease.” Although the importance of trappin‐2 in several chronic infections has been demonstrated, its potential involvement in periodontitis remains undefined. This study aims to investigate salivary levels of trappin‐2 and interleukin (IL)‐1β in periodontally healthy individuals and patients with gingivitis or generalized chronic periodontitis (CP) or aggressive periodontitis (GAgP).

2 Methods

Whole unstimulated saliva samples were collected from 80 systemically healthy and non‐smoking individuals before full‐mouth periodontal examination. Trappin‐2 and IL‐1β were analyzed by enzyme‐linked immunosorbent assay and reported as nanograms per milligram after calibration for total protein levels.

3 Results

Correlation analysis revealed negative association between trappin‐2 and IL‐1β levels. Trappin‐2 also showed strong negative correlation with clinical periodontal parameters, in contrast to IL‐1β, which showed positive correlation. Trappin‐2 levels were significantly lower in individuals with CP and GAgP, but not gingivitis, compared with healthy individuals. Reduced salivary concentrations of trappin‐2 had high sensitivity and specificity to distinguish health from periodontitis.

4 Conclusions

Trappin‐2 is abundant in the saliva of individuals with healthy periodontium in line with its role as an “anti‐alarm” protease. Decreased salivary trappin‐2 and increased IL‐1β levels in individuals with periodontitis, compared with healthy individuals, may implicate a potential antiprotease/proinflammatory cytokine imbalance, resulting in impaired host protective capacity.     

Inflammation and Genetic Risk Indicators for Early Periodontitis in Adults

Background: This report is a further analysis of a study designed to determine clinical and microbial risk indicators for progressing periodontitis. Methods: One hundred ninety subjects who were periodontally healthy or had early signs of periodontitis (age range: 20 to 40 years) were monitored clinically at 6‐month intervals followed by supragingival cleaning. At each visit, gingival crevicular fluid (GCF) and blood were collected for determination of interleukin (IL)‐1β content (in GCF) and IL‐1 genotype (in blood). Interproximal sites with a >1.5‐mm increase in clinical attachment over 18 months were considered disease active. Characteristics were compared between active and inactive subjects. Results: IL‐1β levels in GCF increased with the severity of disease and correlated well with clinical signs of incipient disease. However, the IL‐1 genotype did not show any significant associations with disease or the extent of disease. Conclusion: Indicators of inflammation may be important clinical determinants of future periodontal disease progression, but the IL‐1 genotype was not a risk indictor for early (slight) periodontitis as defined in this subject population.     

Association of interleukin-1 gene polymorphisms with early-onset periodontitis

Background, aims: Early onset periodontal diseases (EOP) are a group of inflammatory disorders characterised by a rapid rate of periodontal tissue destruction, in young individuals who are otherwise healthy. There is now substantial evidence to suggest that genetic factors play a rôle in the pathogenesis of EOP but the precise nature of these factors remains unclear. Polymorphisms in cytokine genes which may underpin inter‐individual differences in cytokine synthesis and secretion have been associated with other diseases which have an inflammatory pathogenesis, including chronic adult periodontal disease (CAPD). Method: We therefore investigated the frequency of polymorphisms in the genes encoding interleukin‐1β (IL‐1β) and its receptor antagonist (IL‐1RA) in 70 EOP patients, including a subgroup of 21 localised EOP (L‐EOP) patients and 72 periodontally healthy controls. All subjects were of Caucasian heritage and systemically healthy. A single nucleotide polymorphism (SNP) in exon 5 of the IL‐1β gene (IL‐1β⁺³⁹⁵³) was analysed by amplifying the polymorphic region using PCR, followed by restriction digestion with Taq1 and gel electrophoresis. Results: The frequency of IL‐1β genotypes homozygous for allele 1 (corresponding to the presence of a restriction site) of the IL‐1β⁺³⁹⁵³ SNP was found to be significantly increased in EOP patients (χ² test, p=0.025). Upon stratification for smoking status a significant difference was found in the IL‐1β genotype distribution between EOP smokers compared to control smokers (F‐exact test, p=0.02), but not between EOP non‐smokers and control non‐smokers. The IL‐1β 1/1 genotype occurred at a higher frequency in EOP smokers (odds ratio=4.9) compared to control smokers. A variable number tandem repeat polymorphism (VNTR) in intron 2 of the IL‐1RA gene was analysed by amplifying the polymorphic region using PCR and fragment size analysis by gel electrophoresis. There was no evidence for an association of an IL‐1RA genotype with EOP. However the combination of IL‐1β allele 1 and IL‐1RA allele 1 (corresponding to 4 repeats) was associated with EOP (Clump, p=0.01). Conclusions: These findings suggest that an IL‐1β genotype in combination with smoking, and a combined IL‐1β and IL‐1RA genotype are risk factors for EOP and support a role for genetic and environmental factors in susceptibility to EOP.     

Salivary Colony Stimulating Factor‐1 and Interleukin‐34 in Periodontal Disease

Background: Colony‐stimulating factor (CSF)‐1 and interleukin (IL)‐34 are macrophage growth factors and regulators of osteoclastogenesis. Their potential involvement in periodontal disease is yet unknown. The aim of this study is to explore the presence of CSF‐1 and IL‐34 in whole saliva in relation to periodontal disease. Methods: Protocol validation was assessed in saliva of healthy donors (n = 21) by enzyme‐linked immunosorbent assay. Salivary CSF‐1, IL‐34, and matrix metalloproteinase (MMP)‐8, a biomarker candidate of periodontitis, were determined in 48 patients (29 patients with periodontitis, 12 with gingivitis, and seven healthy patients) and related to the following clinical periodontal parameters: bleeding on probing, probing depth, clinical attachment loss, and plaque index. An additional separate group of patients with gingivitis (n = 21) and some of the patients with periodontitis (n = 11) were subjected to non‐surgical periodontal treatment, whereupon changes in salivary CSF‐1, IL‐34, and MMP‐8 levels were determined and related to periodontal outcome. Results: Patients with periodontitis displayed higher CSF‐1 and MMP‐8 levels in saliva compared with healthy patients, and IL‐34 levels were lower. A higher CSF‐1/IL‐34 ratio was observed in patients with periodontitis compared with healthy patients. There was a positive correlation between CSF‐1 and MMP‐8, which both correlated negatively to IL‐34, in patients with gingivitis and periodontitis. Clinical periodontal parameters correlated positively with CSF‐1, MMP‐8, and with the CSF‐1/IL‐34 ratio, and negatively with IL‐34 in patients with periodontitis. After treatment CSF‐1 and MMP‐8 levels decreased together with observed clinical improvement in patients with gingivitis. Conclusion: CSF‐1 and IL‐34 are present in saliva and seem to have complementary roles in periodontal disease: IL‐34 in steady‐state and CSF‐1 in inflammation.     

Alcohol Consumption and Periodontitis: Quantification of Periodontal Pathogens and Cytokines

Background: There are few studies on periodontal status related to microbiologic and immunologic profiles among individuals not or occasionally using alcohol and those with alcohol dependence. The aim of this study is to determine the effect of alcohol consumption on the levels of subgingival periodontal pathogens and proinflammatory cytokines (interleukin [IL]‐1β and tumor necrosis factor [TNF]‐α) in the gingival fluid among individuals with and without periodontitis. Methods: This observational analytic study includes 88 volunteers allocated in four groups (n = 22): individuals with alcohol dependence and periodontitis (ADP), individuals with alcohol dependence and without periodontitis (ADNP), individuals not or occasionally using alcohol with periodontitis (NAP), and individuals not or occasionally using alcohol without periodontitis (NANP). Levels of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Eikenella corrodens, and Fusobacterium nucleatum were determined by real‐time polymerase chain reaction on the basis of the subgingival biofilm, and IL‐1β and TNF‐α were quantified by enzyme‐linked immunosorbent assay in gingival fluid samples. Results: Individuals with alcohol dependence showed worse periodontal status and higher levels of P. intermedia, E. corrodens, F. nucleatum, and IL‐1β than non‐users. No significant correlations between TNF‐α and bacterial levels were observed. However, in the ADP group, higher levels of E. corrodens were correlated with higher levels of IL‐1β. Conclusion: A negative influence of alcohol consumption was observed on clinical and microbiologic periodontal parameters, as well as a slight influence on immunologic parameters, signaling the need for additional studies.     

Interleukin‐1 β, interleukin‐12 and interleukin‐18 levels in gingival fluid and serum of patients with gingivitis and periodontitis

Introduction: Cytokines are of major importance in periodontal disease progression. Interleukin‐12 (IL‐12) stimulates interferon‐γ production by T helper type 1 (Th1) cells while IL‐18 induces Th1 responses when present with IL‐12 but Th2 responses in the absence of IL‐12. IL‐1β has been correlated with periodontal disease destruction. This study determined the local concentrations of these cytokines in sites of gingivitis and periodontitis. Methods: Gingival crevicular fluid was collected from two sites in each of 10 gingivitis patients and from two gingivitis sites and two periodontitis sites from each of 10 periodontitis patients. Serum samples were also collected. IL‐1β, biologically active IL‐12 p70, the IL‐12 p40 subunit and IL‐18 concentrations were determined by enzyme‐linked immunoabsorbent assay. Results: IL‐1β and IL‐18 concentrations were higher in the gingival crevicular fluid from periodontitis patients than in that from gingivitis patients; IL‐18 concentrations were higher than those of IL‐1β. Very little IL‐12, either p40 or p70, was detected in the gingival crevicular fluid samples. In the serum, very low levels of cytokines were found. The level of serum IL‐12 p40, however, was higher than in the fluid from periodontitis sites of periodontitis patients. Conclusion: The local production of IL‐1β and IL‐18 in the gingival crevicular fluid increased with increasing inflammation and IL‐18 was the predominant cytokine at both gingivitis and periodontitis sites. Very little IL‐12 was detected with levels decreasing with increasing inflammation. These results suggest that there is an association between severity of periodontal disease and levels of IL‐1, IL‐12 and IL‐18.     

Herpesviruses in human periodontal disease

Recent studies have identified various herpesviruses in human periodontal disease. Epstein–Barr virus type 1 (EBV‐1) infects periodontal B‐lymphocytes and human cytomegalovirus (HCMV) infects periodontal monocytes/macrophages and T‐lymphocytes. EBV‐1, HCMV and other herpesviruses are present more frequently in periodontitis lesions and acute necrotizing ulcerative gingivitis‐lesions than in gingivitis or periodontally healthy sites. Reactivation of HCMV in periodontitis lesions tends to be associated with progressing periodontal disease. Herpesvirus‐associated periodontitis lesions harbor elevated levels of periodontopathic bacteria, including Acrinobacillus actinomycetemcomitans , Porphyromonas gingivalis , Bacteriodes forsythus , Prevotella intermedia , Prevotella nigrescens and Treponema denticola . It may be that active periodontal herpesvirus infection impairs periodontal defenses, thereby permitting subgingival overgrowth of periodontopathic bacteria. Alteration between latent and active herpesvirus infection in the periodontium might lead to transient local immunosuppression and explain in part the episodic progressive nature of human periodontitis. Tissue tropism of herpesvirus infections might help explain the localized pattern of tissue destruction in periodontitis. Absence of herpesvirus infection or viral reactivation might explain why some individuals carry periodontopathic bacteria while still maintaining periodontal health. Further studies are warranted to delineate whether the proposed herpesvirus‐periodontopathic bacteria model might account for some of the pathogenic features of human periodontal disease.     

Influence of smoking on interleukin-1beta level, oxidant status and antioxidant status in gingival crevicular fluid from chronic periodontitis patients before and after periodontal treatment

Toker H, Akp?nar A, Ayd?n H, Poyraz O. Influence of smoking on interleukin‐1beta level, oxidant status and antioxidant status in gingival crevicular fluid from chronic periodontitis patients before and after periodontal treatment. J Periodont Res 2012; 47: 572–577. © 2012 John Wiley & Sons A/S Background and Objective: The aim of this study was to evaluate the impact of smoking on the relationship between interleukin‐1 (IL‐1β) and oxidation in patients with periodontitis and response to nonsurgical periodontal therapy. Material and Methods: Data were obtained from 30 patients with generalized chronic periodontitis (15 smokers and 15 nonsmokers) and from 10 periodontally healthy controls. IL‐1β level, total oxidant status (TOS) and total antioxidant status (TAS) were recorded in gingival crevicular fluid. Probing depth, clinical attachment level, gingival and plaque indices and bleeding on probing were also measured. The gingival crevicular fluid and clinical parameters were recorded at baseline and 6 wk after periodontal treatment. Results: The study showed statistically significant improvement of clinical parameters in both smokers and nonsmokers after periodontal treatment. Moreover, the baseline IL‐1β levels were significantly higher in smokers compared with nonsmokers (p < 0.05). After periodontal treatment, the IL‐1β levels were significantly reduced in both smokers and nonsmokers (p < 0.05). There were no significant differences in TOS and TAS between periodontitis patients and healthy controls at baseline and 6 wk after periodontal treatment. The level of IL‐1β in gingival crevicular fluid was positively correlated with TOS in both smokers and nonsmokers. Conclusions: Periodontal treatment improved the clinical parameters in both smokers and nonsmokers. The results confirm that periodontal therapy has an effect on IL‐1β levels in gingival crevicular fluid, but not on TOS and TAS.     

Comparison of CCL28, interleukin‐8, interleukin‐1β and tumor necrosis factor‐alpha in subjects with gingivitis,chronic periodontitis and generalized aggressive periodontitis

Background and Objective: Cytokines produced by various cells are strong local mediators of inflammation. Mucosa‐associated epithelial chemokine (CCL28), interleukin‐8 (IL‐8), interleukin‐1beta (IL‐1β) and tumor necrosis factor‐alpha (TNF‐α) are major cytokines that play important roles in the periodontal inflammatory process. In this study we aimed to compare the levels of CCL28, IL‐8, IL‐1β and TNF‐α in the gingival crevicular fluid of both periodontally healthy subjects and in subjects diagnosed with gingivitis, chronic periodontitis and generalized aggressive periodontitis. Material and Methods: A total of 84 subjects participated in the study: 21 subjects had gingivitis, 21 subjects had chronic periodontitis, 21 subjects had generalized aggressive periodontitis and 21 were periodontally healthy. The levels of CCL28, IL‐8, IL‐1β and TNF‐α were analyzed using enzyme‐linked immune sorbent assay (ELISA). Results: The total levels of CCL28 and IL‐8 in the gingival crevicular fluid of the generalized aggressive periodontitis group (324.74 ± 42.62 pg/30 s, 487.62 ± 49.21 pg/30 s) were significantly higher than those of the chronic periodontitis group (268.81 ± 28.64 pg/30 s, 423.65 ± 35.24 pg/30 s), the gingivitis group (146.35 ± 17.46 pg/30 s, 310.24 ± 48.20 pg/30 s) and the periodontally healthy group (92.46 ± 22.04 pg/30 s, 148.41 ± 24.64 pg/30 s). Similarly, the total levels of IL‐1β and TNF‐α in the generalized aggressive periodontitis group (110.23 ± 9.20 pg/30 s, 1284.46 ± 86.32 pg/30 s) were significantly higher than those in the chronic periodontitis group (423.65 ± 35.24 pg/30 s, 82.64 ± 9.12 pg/30 s), the gingivitis group (52.10 ± 7.15 pg/30 s, 824.24 ± 44.68 pg/30 s) and the periodontally healthy group (36.44 ± 8.86 pg/30 s, 628.26 ± 34.61 pg/30 s). Conclusion: CCL28, IL‐8, IL‐1β and TNF‐α may play key roles in the host response to inflammation in periodontal diseases. As the severity of periodontal diseases increases, destruction of periodontal tissues also increases. Inflammation is one among many factors that trigger periodontal tissue destruction. Identification of the mediators that influence the development and progression of inflammation in periodontal diseases may be very important in understanding the prognoses of periodontal diseases.     

Adjunctive Non‐Surgical Therapy of Inflamed Periodontal Pockets During Maintenance Therapy Using Diode Laser: A Randomized Clinical Trial

Background: Numerous studies have documented the clinical outcomes of laser therapy for untreated periodontitis, but very few have reported on lasers treating inflamed pockets during maintenance therapy. The aim of this study is to compare the effectiveness of scaling and root planing (SRP) plus the adjunctive use of diode laser therapy to SRP alone on changes in the clinical parameters of disease and on the gingival crevicular fluid (GCF) inflammatory mediator interleukin‐1β (IL‐1β) in patients receiving regular periodontal maintenance therapy. Methods: This single‐masked and randomized, controlled, prospective study includes 22 patients receiving regular periodontal maintenance therapy who had one or more periodontal sites with a probing depth (PD) ≥5 mm with bleeding on probing (BOP). Fifty‐six sites were treated with SRP and adjunctive laser therapy (SRP + L). Fifty‐eight sites were treated with SRP alone. Clinical parameters, including PD, clinical attachment level (CAL), and BOP, and GCF IL‐1β levels were measured immediately before treatment (baseline) and 3 months after treatment. Results: Sites treated with SRP + L and SRP alone resulted in statistically significant reductions in PD and BOP and gains in CAL. These changes were not significantly different between the two therapies. Similarly, differences in GCF IL‐1β levels between SRP + L and SRP alone were not statistically significant. Conclusion: In periodontal maintenance patients, SRP + L did not enhance clinical outcomes compared to SRP alone in the treatment of inflamed sites with ≥5 mm PD.