Aggressive Periodontitis Group Research Articles

Analysis of short chain fatty acids in gingival crevicular fluid of patients with aggressive periodontitis

To investigate 7 short chain fatty acids (SCFA) concentrations in gingival crevicular fluid (GCF) of aggressive periodontitis (AgP) and to analyze the relationship between levels of SCFA and AgP clinical parameters. GCF was collected from 152 sites of 38 AgP patients and 56 sites of 14 healthy subjects. Formic acid, succinic acid, acetic acid, lactic acid, propionic acid, butyric acid and isovalerianic acid were detected by high performance capillary electrophoresis. The concentrations of succinic acid, acetic acid, lactic acid, propionic acid, butyric acid and isovalerianic acid in GCF were significantly higher in AgP patients than in healthy group, while formic acid was lower in GCF of AgP group compared with healthy group. Correlation analysis showed that formic acid was negatively correlated with bleeding index (BI), probing depth (PD) and attachment loss (AL), while BI was positively correlated with succinic acid, acetic acid, lactic acid, propionic acid and butyric acid; PD and AL were positively correlated with succinic acid, acetic acid, propionic acid, butyric acid and isovalerianic acid. The elevation of succinic acid, acetic acid, propionic acid, butyric acid and isovalerianic acid concentrations in GCF may be related with AgP destruction condition, while formic acid concentration was reduced.

Polymorphism in the promoter region of the gene for 5-HTT in individuals with aggressive periodontitis

Susceptibility to and development of periodontal disease have been associated with psychological conditions. Previous studies have associated the presence of polymorphism in the promoter region of the serotonin transporter with several behavioral traits and psychological conditions such as depression, anxiety, and stress. The short allele S has a reduced transcriptional efficiency and is associated with lowered serotonin expression and uptake. The purpose of the present study was to investigate the association between 5-HTTLPR polymorphism and aggressive periodontitis in a sample of Brazilian individuals. This study involved 61 individuals affected by aggressive periodontitis and 71 without periodontitis. Genomic DNA was obtained from oral swabs, amplified by polymerase chain reaction (PCR), and genotyped at 5-HTTLPR. The Chi-square test and multivariate logistic regression were used for statistical analysis. The aggressive periodontitis group displayed a significantly higher occurrence of genotype SS (P < 0.01) and of allele S (P < 0.01). After adjustment for gender and age, it was observed that genotype SS occurred 8 times more frequently in this group. Our findings suggest that 5-HTTLPR polymorphism might be associated with aggressive periodontitis in the Brazilian population.

Human β defensin‐1 and ‐2 expression in the gingiva of patients with specific periodontal diseases

beta defensin antimicrobial peptides are important in epithelial innate immunity, and their differential expression is associated with periodontal diseases. The aims of this study were to determine the mRNA expression of human beta defensin-1 and -2 in the gingival tissue of patients with gingivitis, aggressive periodontitis and chronic periodontitis, and to evaluate the relationship between defensin expression and type and/or severity of periodontal destruction. Fifteen patients in each group with gingivitis, aggressive periodontitis and chronic periodontitis, and 10 healthy subjects, were included in the study (n=55). The periodontal status of the subjects was determined by periodontal clinical measurements and radiographical evaluations. Transcriptional levels of human beta defensin-1 and -2 genes in gingival samples were assessed by using the quantitative real-time polymerase chain reaction technique, and the data were evaluated statistically by the relative expression Software Tool 2 for groupwise comparisons. Expression of the human beta defensin-1 gene was lower in gingivitis and aggressive periodontitis groups, and significantly higher in the chronic periodontitis group, than in the control group (p<0.001). Human beta defensin-2 mRNA expression in the gingivitis group was lower than in the control group; however, the difference was statistically significant only in half of the gingivitis patients (p<0.001). Human beta defensin-2 mRNA levels were higher in some chronic periodontitis patients, but lower in the others when compared with the control group (p<0.001). Expression of the human beta defensin-2 gene increased in the aggressive periodontitis group relative to the control group. This study suggests that human beta defensin-1 and -2 genes in the gingival epithelium show differential expression in patients with specific periodontal diseases, and aggressive and chronic periodontitis types demonstrate different gingival beta defensin-1 and -2 expression patterns.

Gingival crevicular fluid levels of RANKL and OPG in periodontal diseases: implications of their relative ratio

Receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) are a system of molecules that regulate bone resorption. This study aims to compare the levels of RANKL, OPG and their relative ratio in gingival crevicular fluid (GCF) of healthy and periodontal disease subjects. GCF was obtained from healthy (n=21), gingivitis (n=22), chronic periodontitis (n=28), generalized aggressive periodontitis (n=25) and chronic periodontitis subjects under immunosuppressant therapy (n=11). RANKL and OPG concentrations in GCF were measured by enzyme-linked immunosorbent assays. RANKL levels were low in health and gingivitis groups, but increased in all three forms of periodontitis. OPG levels were higher in health than all three periodontitis, or gingivitis groups. There were no differences in RANKL and OPG levels between chronic and generalized aggressive periodontitis groups, whereas these were lower in the immunosuppressed chronic periodontitis group. The RANKL/OPG ratio was significantly elevated in all three periodontitis forms, compared with health or gingivitis, and positively correlated to probing pocket depth and clinical attachment level. GCF RANKL and OPG levels were oppositely regulated in periodontitis, but not gingivitis, resulting in an enhanced RANKL/OPG ratio. This ratio was similar in all three periodontitis groups and may therefore predict disease occurrence.

The IL1A (−889) gene polymorphism is associated with chronic periodontal disease in a sample of Brazilian individuals

It has been proposed that genotypes reflective of polymorphisms in cytokine genes can predispose individuals to disease by enhancing inflammatory processes. The C/T polymorphism at position -889 of the IL1A gene influences interleukin-1alpha expression, with the T allele inducing higher expression. The aim of this study was to evaluate the association of the IL1A (-889) gene polymorphism in Brazilian individuals with different clinical forms of periodontitis and severity of disease. DNA was obtained from oral swabs of 163 Brazilian individuals and was amplified using the polymerase chain reaction (PCR). Products were submitted to digestion and were analyzed by electrophoresis to distinguish the C and T alleles. A significant difference in the genotype distribution was observed when comparing the chronic periodontitis group with the control group, evaluating only nonsmokers (chi-squared analysis = 9.91; p = 0.007), as well as when smokers were included (chi-squared analysis = 6.36; p = 0.04). Moreover, we observed a higher incidence of the T allele in the chronic periodontitis group (37.8%) when compared with the control group (18.4%) in nonsmokers (p = 0.006, odds ratio = 2.69, confidence interval = 1.27-5.68) and also when smokers were included (p = 0.03, odds ratio = 1.87, confidence interval = 0.98-3.56). No statistical difference was observed when the aggressive periodontitis group was compared with the control group. With regard to severity of disease, no statistical difference was observed. These data show an association of the IL1A (-889) polymorphism with chronic periodontitis in Brazilian individuals.

Gingival crevicular fluid matrix metalloproteinase‐13 levels and molecular forms in various types of periodontal diseases

The purpose of this study was to evaluate the levels, molecular forms and activation degree of matrix metalloproteinase-13 (MMP-13) in the gingival crevicular fluid (GCF) of patients with periodontal diseases and to correlate these findings with periodontal clinical parameters. Sixty one subjects participated in this study as healthy (n = 18), gingivitis (n = 17), aggressive periodontitis (AgP; n = 15) and chronic periodontitis (CP; n = 11) groups. Clinical measurements and GCF samples were obtained from each subject. The molecular forms of MMP-13 in GCF samples were analyzed by Western immunoblotting method. Differences among the groups were assessed using non-parametric statistical analysis. In the CP group, levels of 29-30 kDa fragment of MMP-13, total MMP-13, and activated form of MMP-13 were significantly higher than in the healthy, gingivitis and AgP groups. GCF levels of all molecular forms of MMP-13 in AgP group were similar to those of healthy and gingivitis groups. Total and activated MMP-13 levels were positively correlated with all clinical parameters. 29-30 kDa fragment levels of MMP-13 were also positively correlated with papillary bleeding index and plaque index. These results indicate that elevated GCF MMP-13 levels may play an important role in the pathogenesis of CP. These data demonstrate, for the first time, pathologically activated and elevated MMP-13 in GCF.

CARD15 gene variants in aggressive periodontitis

The CARD15 gene encodes a protein that acts as an intracellular receptor of bacterial products, thus playing an important role in the innate immune response. Recently, CARD15 gene variants have been identified as a cause of increased susceptibility to Crohn's disease. The present study aimed to examine a potential association of CARD15 gene variants with aggressive periodontitis susceptibility. The three main known CARD15 gene variants (p.R702W, p.G908R, and p.L1007fsX1008) were analysed by direct sequencing of exon 4, 8, and 11 of the gene in a total of 86 generalized aggressive periodontitis patients in comparison with 67 healthy controls. The mutant allele frequencies of the CARD15 variants were low in the generalized aggressive periodontitis group as well as in the control group and not significantly different (R702W: 3.5% versus 5.2%; G908R: 1.7% versus 1.5%; L1007fsX1008: 5.2% versus 4.5%). Two rare variants (A755V and R791Q), previously described only in patients with other inflammatory diseases, were observed in three patients having aggressive periodontitis but not in controls. Unlike in Crohn's disease, our results did not show an association between the three main CARD15 mutations and aggressive periodontitis. The role of rare variants remains unclear.

Modulation of clinical expression of plaque‐induced gingivitis: response in aggressive periodontitis subjects

The aim of this study was to characterize the gingival inflammatory response to de novo plaque accumulation in subjects treated for aggressive periodontitis (AP). The gingival inflammatory response of the AP subjects was retrospectively compared with that of periodontally healthy individuals (PH) matched for exposure to plaque and of periodontally healthy subjects previously identified as "high responders" (HR) and "low responders" (LR). 13 AP subjects and 26 matched PH subjects participated in a 21-day experimental gingivitis trial. Plaque index (PlI), Gingival index (GI), gingival crevicular fluid volume (GCF) and angulated bleeding score (AngBS) were recorded at days 0, 7, 14 and 21. Cumulative plaque exposure (CPE), i.e. PlI over time, was also calculated. GCF was significantly higher in AP compared with PH group at each observation interval (p< or =0.001). In addition, GCF was significantly higher in AP group compared with either LR or HR groups at each observation interval (p<0.001). These results suggest that susceptibility to gingival inflammation in response to de novo plaque accumulation may be related to susceptibility to periodontitis.

Gingival Crevicular Fluid Levels of Monocyte Chemoattractant Protein‐1 and Tumor Necrosis Factor‐Alpha in Patients With Chronic and Aggressive Periodontitis

Monocyte chemoattractant protein-1 (MCP-1) is a well-known chemotactic cytokine that regulates mononuclear inflammatory cell recruitment. This recruitment has particular importance in the oral cavity because inflammatory cells will be challenged with periodontopathogenic bacteria during infections. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces bone resorption by stimulating proliferation and differentiation of osteoclasts' progenitors and also stimulates MCP-1 expression. The aims of this study were to investigate the presence of MCP-1 in gingival crevicular fluid (GCF) samples from patients with chronic periodontitis (CP) and aggressive periodontitis (AgP) and to examine the possible correlations between the GCF levels of MCP-1 and TNF-alpha. Twenty-five CP, 20 AgP, and 20 healthy control (C) patients were selected for the study. Plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) measurements were recorded from each sampling area. Assays for GCF MCP-1 and TNF-alpha were carried out by an enzyme-linked immunosorbent assay (ELISA) method. The concentration (nanograms per microliters) and total MCP-1 and TNF-alpha (nanograms per site) were not statistically significant between CP and AgP groups, but total MCP-1 and TNF-alpha was statistically different between CP and C and between AgP and C groups (P <0.001). All clinical parameters were statistically different between CP and C and between AgP and C groups (P <0.001). A positive statistical correlation was detected between the levels of MCP-1 and TNF-alpha, and there was also a positive correlation between all clinical parameters and total MCP-1 and TNF-alpha levels. These results suggest that MCP-1 could have an important role in the activation and recruitment of inflammatory and immune cells in periodontal diseases, and both AgP and CP patients may have the same pattern of MCP-1 expression. A strong positive correlation between the GCF levels of MCP-1 and TNF-alpha may account for the mechanism of amplification of inflammatory events in gingival inflammation.

A functional interleukin‐1β gene polymorphism is associated with chronic periodontitis in a sample of Brazilian individuals

Interleukin-1 beta (IL-1 beta) is a potent inflammatory mediator and an important polymorphism in the locus +3954 (C/T) of the human IL1 B gene has been shown to affect the levels of this cytokine. This functional polymorphism has been associated with the establishment of inflammatory diseases, including periodontal disease, in European, Asian and North American populations. The aim of this study was to investigate the association between the IL1 B (+3954) gene polymorphism and the occurrence of different clinical forms of periodontitis in a sample of Brazilian individuals. This study employed a cross-sectional design involving individuals from the State of Minas Gerais in the south-eastern region of Brazil. Genomic DNA was obtained from oral swabs of 129 individuals and amplified using the polymerase chain reaction (PCR) with specific primers flanking the locus +3954 of IL1 B. PCR products were submitted to restriction endonuclease digestion and analyzed by polyacrylamide gel electrophoresis, to distinguish alleles T and C of the IL1 B gene, allowing for the determination of the genotypes and detection of the polymorphism. The chronic periodontitis group displayed a higher percentage of the T allele (28%) when compared to the aggressive periodontitis group (10.7%, chi(2)=5.24, p=0.02, OR=0.31, CI=0.11--0.88) and to control group (8.7%, chi(2)=7.11, p=0.007, OR=0.24, CI=0.08--0.73). Our data suggested that the polymorphism in the locus +3954 of IL1 B gene could be a risk factor for chronic periodontitis in a sample of Brazilian individuals.

Immunohistochemical analysis of soft tissues in implants with healthy and peri‐implantitis condition, and aggressive periodontitis

Today, implant-supported prostheses are widely accepted as a reliable treatment modality, but failures in longitudinal studies have been shown. In some cases, peri-implantitis with a progressive periodontal bone loss takes place, and mechanical or load factors and biological or plaque-induced lesions have been claimed as main etiologic factors. We compared five cases of peri-implantitis, with five cases of healthy peri-implant tissues and five cases of aggressive periodontitis in order to give new findings on the osseointegration loss process. Biopsy specimens from the peri-implant tissues including oral (O), sulcular, and junctional epithelium and the underlying and supracrestal connective tissue, were taken in all cases for histological and immunohistochemical analysis. T lymphocytes were the most prominent cell in the peri-implantitis (PG) and aggressive periodontitis (AG) groups, but not in the peri-implant healthy group (HG). CD1a-positive cells (Langerhans and immature dendritic cells) were observed more frequently in the O than in the sulcular-junctional (S-J) epithelium: they were located in the basal and parabasal layers, without any differences between the three groups. Vascular proliferation analysed by immunoreactivity for CD34, Factor VIII, and vascular endothelial growth factor was more prominent in the PG comparing with HG and AG in the S-J area. Apoptosis, analysed by bcl2 and p53 immunoreactivity, was similar in the three groups. In conclusion, we suggest that the osseointegration loss process is due to an inflammatory process similar to that observed in aggressive periodontitis according to the number of T lymphocytes, but not to the vascular proliferation.

Relative Proportions of T‐Cell Subpopulations and Cytokines That Mediate and Regulate the Adaptive Immune Response in Patients With Aggressive Periodontitis

Both the virulence factors of periodontopathic bacteria and the immune response against them have been involved in tissue destruction observed in periodontal disease. Considering the regulatory role of cytokines produced by T cells, the purpose of this study was to compare the CD3+, CD4+, and CD8+ subpopulations of T cells, and to characterize the mRNA of cytokines involved in the adaptive immune response in a group of healthy/gingivitis 1 (HI/G1) individuals and aggressive periodontitis (AgP) patients. The percentages of T-cell subpopulations were analyzed in 10 gingival samples of HI/G1 individuals and 10 gingival samples of AgP patients by immunohistochemistry. The presence of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-5, IL-10, IL- 13, and transforming growth factor (TGF)-beta was measured by reverse transcription polymerase chain reaction (RT-PCR) of mRNA extracted from complete gingival biopsies. Significant differences were found in CD3+ and CD4+ cell counts between both groups. The parameters were lower in the gingival biopsies from AgP patients while CD8+ counts were similar in both groups. The cytokine mRNA analysis showed constant expression of IL-2 and IFN-gamma in all cases. The mRNA of IL-5 and IL-10 was present in the majority of HI/G1 (N = 10, N = 9, respectively) but was not in the AgP group (N = 2, N = 1). IL-13 and TGF-beta were only detected in HI/G1 (N = 2, N = 3) and IL-4 was not detected in any of the individuals. These results indicate that the role of the CD8+ subpopulation in aggressive periodontitis lesions is limited. On the other hand, cytokines IL-2 and IFN-gamma may not be relevant in the progression of aggressive periodontitis.

A novel polymorphism of FcalphaRI (CD89) associated with aggressive periodontitis.

Immunoglobulin A Fc receptor (FcalphaRI) has been implicated in the pathogenesis of periodontitis, because increased IgA responses and FcalphaRI-bearing neutrophils are observed in the disease lesions. Inter-individual differences in susceptibility to periodontitis may be attributable to genetic variability in FcalphaRI-mediated immunity. We here identified an FcalphaRI novel polymorphism (nt 324 A-to-G transition) in the membrane-distal extracellular domain encompassing the ligand-binding site, not resulting in an amino acid change. We compared the FcalphaRI genotype distributions among 46 Japanese aggressive periodontitis (AGP) patients, 80 race-matched healthy controls (HCs), and 59 Caucasian HCs. No ethnic differences were observed in the FcalphaRI genotype distributions between Japanese and Caucasian HC. Notably, we observed a difference in the genotype distribution between the AGP and HC groups. Carriage rate of the nt 324 A allele was higher in the AGP (65.2%) than that in the HC group (42.5%) (odds ratio 2.54). Polymorphonuclear neutrophils from peripheral blood and gingival crevicular fluid exhibited a decreased phagocytosis of periodontopathic bacteria (Porphyromonas gingivalis) in the nt 324 A/A patients as compared with the nt 324 G/G patients. These results document a genetic polymorphism at the FcalphaRI ligand-binding site to be associated with susceptibility to AGP.

Total proteoglycan and chondroitin-4-sulfate levels in gingiva of patients with various types of periodontitis.

The aim of the present study was to investigate the total proteoglycan (PG) and chondroitin-4-sulfate (C4S) levels in gingival tissue samples obtained from patients with aggressive periodontitis (AgP) and chronic periodontitis (CP) before therapy (baseline) and 1 month after completion of non-surgical periodontal therapy. Gingival tissue samples were obtained from 10 AgP and 10 CP patients before initiation of treatment (baseline) and 1 month after non-surgical periodontal treatment. The control group comprised 10 systemically and periodontally healthy subjects. Total PG and C4S levels were determined by biochemical techniques. PG levels were analyzed using a modified Bitter and Muir method. C4S assay was carried out using chondroitin sulphate lyase AC and chondroitin-6 sulphate sulphohydrolase enzymes. The results were tested statistically using parametric tests. The clinical periodontal parameters demonstrated significant decreases in the periodontitis groups (P<0.05) after treatment, and there was no significant difference between AgP and CP groups at baseline and after treatment (P>0.05). At baseline, total PG and C4S levels in both of the periodontitis groups were significantly lower than that of the control group (P<0.05). One month after the non-surgical periodontal treatment, total PG levels in the periodontitis groups were comparable to the control group (P>0.05), whereas C4S levels in the AgP group were significantly lower than the other study groups (P<0.05). In the CP group, total PG and C4S levels increased significantly (P = 0.001 and P = 0.006, respectively) after non-surgical periodontal treatment, but they did not increase in the AgP group (P>0.05). The significant increases observed in total proteoglycan and chondroitin-4-sulfate levels after non-surgical periodontal treatment in the CP group but not in the AgP group may suggest that healing patterns differ between the two periodontitis types in terms of PG and C4S composition of extracellular matrix.

Distribution of interleukin-1beta(+3954) and IL-1alpha(-889) genetic variations in a Thai population group.

The severe form of chronic periodontitis (CP) has been reported to be strongly associated with the presence of allele 2 of composite IL-1beta(+3954) and IL-1alpha(-889) genetic polymorphisms (genotype positive). However, other studies have reported conflicting findings, not only on the association between the composite IL-1 gene polymorphisms and CP, but also the link between IL-1 gene polymorphisms and aggressive periodontitis (AgP). These might have resulted from differences in ethnic background and disease entities. The aim of this study was to determine the distribution of IL-1beta(+3954) and IL-1alpha(-889) genetic polymorphisms in a group of Thai subjects based on their periodontal status, including CP, AgP, and healthy groups. A total of 123 Thai subjects were clinically and radiographically assessed for their periodontal status. Blood samples were collected by fingerstick and adsorbed onto filter paper. The IL-1beta(+3954) and IL-1alpha(-889) genotypes were performed by polymerase chain reaction, digested with restriction enzymes, and separated by gel electrophoresis. The distribution of allele 1 homozygous genotype was 97.6% and 84.6% for IL-1beta(+3954) and IL-1alpha(-889), respectively. No allele 2 homozygous genotype was detected in either of these two gene loci. Only 1.6% (2 out of 123) of the subjects were genotype positive, which was too low to determine the association between the composite genotype of IL-1beta(+3954) and IL-1alpha(-889) and severe forms of periodontal disease. Genetic polymorphism of IL-1 genes in these two loci may not be useful in predicting the severity of periodontal disease in the Thai ethnic group.

Neopterin Profile to Evaluate the Effectiveness of Treatment in Aggressive Periodontitis

Abstract Periodontal disease results from the interaction of the host defence mechanisms with the microbial dental plaque. Analysis of gingival crevicular Huid (GCF) provides a non-invasive means of evaluating the role of the host response in periodontal disease. Based on our previous study, demonstrating increased levels of neopterin in GCF and saliva from patients with aggressive periodontitis (AgP), the aim of this study was to evaluate the effect of periodontal treatment on the levels of neopterin in GCF, saliva and urine of patients with AgP. Pre-treatment values of neopterin in GCF were 4.04 ± 0.86 nmol/ml for the AgP group (n=8) and 2.68 ± 0.90 nmol/ml fyr the control group (n=8; difference not significant). After periodontal treatment, the level of ncoptei in was found 2.38 ± 0.72 nmol/ml in the patient group which did not differ f r om pre-treatment levels. The salivary neopterin concentration was higher in both AgP groups (14.14 ± 2.85 nmol/1 and 8.02 ± 3.12 nmol/1, before and after periodontal treatment) than in controls (2.58 ± 0.3 nmol/1; both p&lt;0.05). No significant difference in salivary neopterin level was observed in patients before and after periodontal treatment. Concentrations of urine neopterin in patients before treatment were 188.5 ± 30.98 μηιοί neopterin/mol creatinine and 168.1 + 20.21 μηιοί in controls (difference not significant). Following periodontal treatment, the urinary neopterin levels (310.1 ± 39.82 μηιοί neopterin/mol creatinine) were higher when compared to the baseline levels and to controls (p&lt;0.05). Our results suggest that neopterin in saliva and GCF might be associated with the periodontal diseases process.

Level of neopterin, a marker of immune cell activation in gingival crevicular fluid, saliva, and urine in patients with aggressive periodontitis.

Neopterin, a marker of cellular immune activation, is produced by human macrophages after induction by interferon gamma that is secreted by T lymphocytes. Neopterin concentrations in diverse body fluids have been reported to increase in parallel with bacteria in the clinical course of infections. Therefore, determination of neopterin in body fluids was thought to be useful for predicting the prognosis and diagnosis of aggressive forms of periodontal disease, in which the cell-mediated immune response plays an important role in immunopathogenesis. The aim of the present study was to observe the role of neopterin in the pathogenesis of aggressive periodontitis (AgP). Thirteen individuals who were systemically and periodontally healthy and 16 systemically healthy individuals diagnosed with AgP were recruited for this study. Mixed saliva and urine samples were collected from each subject. Gingival crevicular fluid (GCF) samples were obtained from 6 teeth with > or =5 mm probing depth (PD). After evaluation of GCF amount from paper strips, enzyme-linked immunosorbent assay (ELISA) was employed to determine the amount of neopterin in urine, saliva, and GCF. The amount of neopterin in urine and saliva measured 235.77+/-405.31 micromol neopterin/mol creatinine and 9.85+/-7.66 nmol/l, respectively, for the AgP group and 225.45+/-100.72 micromol neopterin/mol creatinine and 5.25+/-5.76 nmol/l, respectively, for controls. The present data demonstrate that, while salivary neopterin levels were found to be significantly different between periodontitis and control subjects, there were non-significant differences in urine neopterin levels. The amount and concentration of neopterin in GCF measured was 18+/-12.75 nmol/l and 3.67+/-2.40 nmol/ml for the AgP group and 2.51+/-1.72 nmol/l and 3.88+/-4.50 nmol/ml for the control group. When total amounts of neopterin are taken into consideration, a significant difference between AgP and controls is shown; however, no significant difference in net concentration of neopterin was found between both groups. This study is the first report to evaluate the involvement of neopterin in AgP and this might be considered of value in understanding periodontal disease mechanisms.