Host defense against oral microbiota by bone-damaging T cells.

The immune system evolved to efficiently eradicate invading bacteria and terminate inflammation through balancing inflammatory and regulatory T-cell responses. In autoimmune arthritis, pathogenic TH17 cells induce bone destruction and autoimmune inflammation. However, whether a beneficial function of T-cell-induced bone damage exists is unclear. Here, we show that bone-damaging T cells have a critical function in the eradication of bacteria in a mouse model of periodontitis, which is the most common infectious disease. Bacterial invasion leads to the generation of specialized TH17 cells that protect against bacteria by evoking mucosal immune responses as well as inducing bone damage, the latter of which also inhibits infection by removing the tooth. Thus, bone-damaging T cells, which may have developed to stop local infection by inducing tooth loss, function as a double-edged sword by protecting against pathogens while also inducing skeletal tissue degradation.

[Application of immunomodulators in the treatment of mandibular fractures in elderly patients with incomplete secondary adentia].

The aim of the work was to study the experience of using complex pharmacotherapy in the treatment of mandibular fractures in elderly patients with incomplete secondary periodontitis, which were divided into two groups. In the first group, patients (n = 46; average age 69.0 ± 3.6) were treated using the authors' original device combined with application of antimicrobial MetrogilDenta gel onto gums two times a day during ten days. Patients in the second group (n = 52; average age 61.0 ± 3.1) were treated with the same device combined with (i) application of MetrogilDenta antimicrobial gel onto gums two times a day during ten days, (ii) application of 1.5 ml of Cycloferon 5% liniment by cotton pellet for 20 min during the same 10 days (30 minutes after the antimicrobial gel), and (iii) intramuscular injections of 6 mg of synthetic immunomodulator Polyoxidonium once a day for 3 days, then once every two days (for a total of 17 days). It is established that the use of the combination of interferon inducers of immunomodulator group--Cycloferon in the form of liniment and synthetic immunomodulator Polyoksidonium together with MetrogilDenta antimicrobial gel--led to the most pronounced regression of inflammatory and destructive processes in periodontal tissues (in 7.1%, d = 0.05), optimized the state of local immunity of the oral cavity, and normalized microflora in periodontal pockets in elderly patients with incomplete secondary adentia.

Levels of C-reactive protein and protein C in periodontitis patients with and without cardiovascular disease.

Since periodontitis is a chronic and inflammatory disease, a number of hypotheses have proposed that it has an etiological or modulating role in cardiovascular disease (CVD). This study aimed to ascertain the changes in the plasma levels of C-reactive protein (CRP) and protein C (PC), a natural anticoagulant also having an anti-inflammatory effect, in patients who have mild-to-severe periodontitis with or without CVD. The test group consisted of 26 patients with CVD and chronic periodontitis and the control group consisted of 26 patients with chronic periodontitis and no systemic disease. In both groups Community Periodontal Index of Treatment Needs scores were recorded and blood samples were collected. CRP levels were significantly high and PC activity was significantly low in the test group compared to the control group (p < 0.001). There was a negative correlation between tooth loss and PC and between CRP and PC. How PC is affected by the inflammatory events and its association with CRP is an active area of investigation.

Systemic antibiotics and tooth loss in periodontal disease.

Systemic antibiotics have been recommended for the treatment of destructive periodontal disease. Our goal was to relate antibiotic use for medical or dental reasons to subsequent tooth loss in a cohort of 12,631 persons with destructive periodontal disease. After adjustment for age, smoking, and other confounders, the dispensing of antibiotics for 1-13 days, 14-20 days, or 21 or more days was not associated with reduced tooth loss [Adjusted rate ratio (RR) = 1.0; 95% Confidence Interval (CI) = 0.8-1.1; RR = 1.2; 95% CI = 0.9-1.4, and RR =1.2, 95% CI =1.0-1.3, respectively]. Numerous subgroup analyses were consistent with these overall null findings, with two exceptions: Longer courses of tetracyclines were associated with reduced tooth loss among persons receiving periodontal care, and penicillin was associated with reduced tooth loss among persons with more severe disease. Long-term, larger randomized trials are needed to provide evidence that antibiotics reduce tooth loss when used in the management of destructive periodontal disease.

Tooth loss, pancreatic cancer, and Helicobacter pylori.

BACKGROUND: Poor dental health has been associated with increased risks of oral, esophageal, and gastric cancer and may also be associated with pancreatic cancer. In addition, Helicobacter pylori has been found in dental plaque and has been associated with periodontal disease and pancreatic cancer. OBJECTIVE: The objective was to investigate prospectively the relation between dentition history and pancreatic cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort in Finland and the association between dentition history and H. pylori seropositivity in a cross-sectional sample of subjects without cancer (n = 475) from the same cohort. DESIGN: Of the 29,104 male smokers aged 50-69 y in the cohort for whom there were complete data, 174 developed pancreatic cancer from 1985 to 1997. Cox proportional hazard models were used to estimate age-, smoking-, education-, urban living-, and height-adjusted hazard ratios and 95% CIs for pancreatic cancer, and logistic regression models were used to estimate age- and education-adjusted odds ratios for H. pylori carriage. RESULTS: Tooth loss was positively associated with pancreatic cancer (edentulous compared with missing 0-10 teeth: hazard ratio = 1.63; 95% CI: 1.09, 2.46; P for trend = 0.02) but was not significantly associated with H. pylori seropositivity (edentulous compared with missing 0-10 teeth: odds ratio = 1.30; 95% CI: 0.73, 2.32; P for trend = 0.37). CONCLUSION: Additional studies are needed to evaluate the association between tooth loss and pancreatic cancer, as well as cancers at other gastrointestinal sites, particularly with respect to possible biological mechanisms.

Associations of serum concentrations of IgG, IgA, IgM and interleukin-1beta with early-onset periodontitis classification and race.

BACKGROUND: The significance of serum concentrations of various antibodies and cytokines in the pathogenesis of early-onset periodontitis (EOP) is not well understood. Recent reports suggest differences between young blacks and whites in certain humoral responses, regardless of periodontal status. This study was undertaken to compare the serum concentrations of IgG, IgA, IgM, and IL-1beta in EOP subjects with that of healthy controls, and to study the effect of race on these levels. MATERIAL AND METHODS: This case-control study included 228 individuals, 19-25 years old who were selected from a larger population examined in the National Survey of Oral Health of United States Children in 1986/1987. The subjects were classified by their EOP status and they included 166 subjects with EOP and 62 healthy controls. Blood samples were used to assess the serum concentrations of IgG, IgM, IgA, IgG subclass, and IL-1beta. RESULTS: The serum concentrations of IgG, IgG subclasses, IgA, and IgM in blacks were not significantly different in the generalized, localized and incidental EOP groups as compared to the healthy controls. The serum IL-1beta concentration was slightly and uniformly lower in the EOP groups than in the control group, although not statistically significant. Blacks had significantly higher serum concentrations of total IgG, and of IgG1, IgG2 and IgG3 than whites and Hispanics. Hispanics had significantly higher serum concentrations of IgM and IgG4 than whites and blacks. Hispanics also had a significantly higher serum concentration of IL-1beta than blacks. CONCLUSIONS: Total antibody response in blacks is not associated with EOP classification. Race has a significant effect on serum antibody concentrations irrespective of disease classification, with blacks having significantly higher serum concentrations of IgG1, IgG2 and IgG3 than whites and Hispanics.

A critical assessment of interleukin-1 (IL-1) genotyping when used in a genetic susceptibility test for severe chronic periodontitis.

BACKGROUND: This review addresses the ability of a commercially available genetic susceptibility test to determine the risk of developing severe chronic periodontitis. The test is used to detect the simultaneous occurrence of allele 2 at the IL-1A+4845 and IL-1B+3954 loci. If both of these polymorphisms are present, patients are referred to as being genotype-positive and considered predisposed to becoming afflicted with severe chronic periodontitis. A basic premise of this test is the assumption that individuals who are genotype-positive produce increased amounts of IL-beta in response to microbial lipopolysaccharides, which allegedly predisposes them to an exaggerated inflammatory response and an increased incidence of chronic periodontitis. METHODS: Controlled clinical trials were selected that evaluated the ability of the genetic test to predict which patients were susceptible to bleeding upon probing, periodontitis, peri-implantitis, and tooth loss. RESULTS: Comparison of results from test (genotype-positive) and control groups (genotype-negative) revealed that there is ambiguity with regard to predicting which patients will manifest elevated sub-gingival levels of IL-beta. Similarly, it is questionable if the test is able to forecast which individuals will demonstrate an increased occurrence of bleeding upon probing, diminished clinical attachment, decreased osseous support, or loss of teeth. CONCLUSIONS: There are many unanswered questions concerning the utility of detecting allele 2 at the IL-1A+4845 and IL-IB+3954 loci to foretell which patients will develop severe chronic periodontitis. Therefore, clinicians must cautiously interpret results obtained with the commercially available genetic susceptibility test before they alter maintenance schedules or treatment regimens of symptomatic or asymptomatic patients.

Retrospective evaluation of the influence of the interleukin-1 genotype on radiographic bone levels in treated periodontal patients over 10 years.

BACKGROUND: A difference in genetic susceptibility to plaque accumulation has been advocated to explain different responses to periodontal therapy. The purpose of this study is to assess the role of the interleukin-1 (IL-1) polymorphism on the rate of bone and tooth loss in non-smoking periodontally treated patients during maintenance. METHODS: Sixty consecutive non-smoking patients (mean age 46.8 +/- 5.0) with moderate to severe periodontitis, treated and maintained for over 10 years were selected. At baseline (T0), radiographic evaluation (cemento-enamel junction [CEJ]-root apex, CEJ-bottom of defect mesial and distal, CEJ-bone crest mesial and distal, crown-root ratio) was performed. All patients received scaling and root planing; 36 patients then underwent surgical therapy. Subsequently, all patients were enrolled in a periodontal maintenance program with recall visits every 3.4 +/- 1.0 months for at least 10 years. At the latest recall visit (T2) the same radiographic measurements evaluated at baseline were taken and a DNA sample for IL-1 genetic susceptibility testing was collected and sent for analysis. RESULTS: Twenty-three of the 60 patients (38.3%) were IL-1 genotype positive. A total of 52 teeth (3.3%) out of 1,566 were lost due to periodontitis between T0 and T2; 28 of 957 (2.9%) in the IL-1 genotype negative group and 24 of 609 (3.9%) in IL-1 genotype positive group. The mean variation in bone defect level (DeltaBD) averaged -0.04 mm in IL-1 genotype negative patients and 0.01 mm in IL-1 genotype positive patients. The mean variation in bone crest level (DeltaBC) averaged -0.24 mm in IL-1 genotype negative patients and -0.28 mm in IL-1 genotype positive patients. However, a few patients showed significant differences in response to therapy based on initial bone levels and genotype. IL-1 negative patients who showed minimal initial bone loss responded to the therapy better than the IL-1 positive patients. IL-1 positive patients with severe initial bone loss showed a better response to the therapy than IL-1 negative patients. CONCLUSIONS: On average, there were no significant differences related to IL-1 genotype in tooth loss after 10 years in a non-smoking, well-maintained periodontal population. On an individual patient basis, the IL-1 genotype, in combination with the initial bone level, seems useful at the beginning of therapy for predicting bone level variation.

Inflammatory mediators of the terminal dentition in adult and early onset periodontitis.

Based upon the prosthodontic literature, subjects who are at the transition stage between natural dentition and edentulism are called "terminal dentition" (TD) cases. The aim of the present cross-sectional investigation was to characterize the local and systemic inflammatory responses in 2 groups of patients with terminal dentition periodontitis. Eight severe adult periodontitis terminal dentition (AP-TD) subjects and 8 early onset periodontitis terminal dentition (EOP-TD) subjects were entered into the study. Our purpose was to measure an extended battery of cytokines in the gingival crevicular fluid (GCF) and in lipopolysaccharide (LPS)-stimulated monocytic culture supernatants as well as gingival mononuclear cell messenger RNA (mRNA) transcripts determined from biopsy samples. Within the GCF there were 3 tiers (levels) of mediators based upon approximate 10-fold differences in concentration. The highest tier included prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and interleukin-2 (IL-2), the intermediate tier included tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN-gamma) and at the lowest concentration level were interleukin-4 (IL-4) and interleukin-6 (IL-6). Thus, the GCF analysis clearly indicated that in both AP-TD and EOP-TD groups the monocytic, i.e. IL-1 beta and PGE2 and Th1, i.e. IL-2 and IFN-gamma, inflammatory mediator levels quantitatively dominated over the Th2 mediators, i.e. IL-4 and IL-6. LPS-stimulated monocytic release of IL-1 beta, PGE2 and TNF alpha was significantly elevated in both AP-TD and EOP-TD groups compared to those of a control group of 21 subjects with moderate to advanced adult periodontitis. The cytokine mRNA expression of isolated gingival mononuclear cells showed that in both the AP-TD and the EOP-TD groups Th1 and Th2 cytokines were expressed, with low levels of IL-4 and IL-12. In conclusion, our data suggest that this cross-sectional TD periodontitis model may reflect progressive periodontal disease associated with tooth loss. Furthermore, although Th1 cytokine levels in the GCF dominate over the Th2 response, monocytic activation provides the main source of proinflammatory mediators. In addition, LPS-stimulated peripheral blood monocytes demonstrate an upregulated inflammatory mediator secretion in the terminal dentition.

Loss of deciduous teeth and germs of permanent incisors in a 4-year-old child. An atypic prepubertal periodontitis? A clinical, microbiological, immunological and ultrastructural study.

A 4-year-old child was referred, in April 1988, to Rennes Dental School (France) for deciduous tooth mobility with premature loss of 4 deciduous teeth and germs of 2 permanent incisors. Microbiological examinations by culture revealed the presence of the periodontal pathogen Actinobacillus actinomycetemcomitans. Immunofluorescence of plaque samples revealed the presence of Porphyromonas gingivalis that had not been isolated by culture. Neutrophil functions were within normal ranges. Transmission electron microscopy of gingiva showed a disorganised epithelium. The connective tissue was infiltrated by inflammatory cells. The basement membranes were normal, but the connective tissue-epithelium interface was mainly composed of short rete pegs. Scanning electron microscopy of extracted deciduous teeth revealed lack of cementum, lacunae in the cementum and lack of fibrillar insertion on the middle part of the root. Skin lesions, mainly situated on face, were observed. Treatment was by extraction of mobile deciduous teeth combined with 3-week courses of metronidazole. Clinical and microbiological follow-up was continued over a 7-year period. No periodontal lesions have been detected since eruption of the permanent teeth. The present subgingival and lingual microflora (December 1995) is composed of bacteria associated with periodontal health. However, the future appearance of a hitherto undetected systemic disease is still possible.