Salivary calprotectin and neutrophils in inflammatory bowel disease in relation to oral diseases.

OBJECTIVE: Calprotectin is elevated in saliva from inflammatory bowel disease (IBD) patients, but it is also affected by oral disease. We assessed the salivary concentration of calprotectin in IBD patients, in relation to intestinal and oral diseases. Furthermore, we investigated the phenotype of salivary neutrophils from IBD patients, and their ability to secrete calprotectin. MATERIALS AND METHODS: Thirty IBD patients and 26 controls were orally examined and sampled for stimulated saliva. Twenty-five IBD patients provided fresh fecal samples. Calprotectin concentrations in saliva and feces were determined by an enzyme-linked immunosorbent assay. Expression of CD11b, CD15, and CD16 on oral neutrophils was assessed by flow cytometry. Secretion of calprotectin was evaluated in cultured oral neutrophils. RESULTS: Calprotectin was significantly elevated in saliva of IBD patients compared to controls, particularly in Crohn's disease, irrespective of caries or periodontitis. Salivary calprotectin did not correlate to fecal calprotectin. CD11b expression was significantly reduced in salivary neutrophils from IBD patients. Salivary neutrophils from IBD patients tended to secrete more calprotectin than controls. CONCLUSIONS: Salivary calprotectin is elevated in IBD regardless of oral diseases. Furthermore, salivary neutrophils secrete calprotectin, and display lower CD11b expression in IBD.

Effects of intermittent fasting on periodontal inflammation and subgingival microbiota.

BACKGROUND: Studies on the impact of intermittent fasting on periodontal health are still scarce. Thus, this study evaluated the effects of long-term intermittent fasting on periodontal health and the subgingival microbiota. METHODS: This pilot study was part of a nonrandomized controlled trial. Overweight/obese participants (n = 14) entered an intermittent fasting program, specifically the 5:2 diet, in which they restricted caloric intake to about a quarter of the normal total daily caloric expenditure for two nonconsecutive days/week. Subjects underwent a thorough clinical and laboratory examination, including an assessment of their periodontal condition, at baseline and 6 months after starting the diet. Additionally, subgingival microbiota was assessed by 16S rRNA gene sequencing. RESULTS: After 6 months of intermittent fasting, weight, body mass index, C-reactive protein, hemoglobin A1c (HbA1c), and the cholesterol profile improved significantly (p < 0.05). Moreover, significant reductions were observed in bleeding on probing (p = 0.01) and the presence of shallow periodontal pockets after fasting (p < 0.001), while no significant change was seen in plaque index (p = 0.14). While we did not observe significant changes in α- or ß-diversity of the subgingival microbiota related to dietary intervention (p > 0.05), significant differences were seen in the abundances of several taxa among individuals exhibiting ≥60% reduction (good responders) in probing pocket depth of 4-5 mm compared to those with <60% reduction (bad responders). CONCLUSION: Intermittent fasting decreased systemic and periodontal inflammation. Although the subgingival microbiota was unaltered by this intervention, apparent taxonomic variability was observed between good and bad responders.

Immune cell composition and inflammatory profile of human peri-implantitis and periodontitis lesions.

Peri-implantitis (PI) and periodontitis (PD) are common oral inflammatory diseases, which seem to exhibit critical differences in some of their molecular features. Thus, we assessed the immune cell composition of PI and PD lesions and the corresponding inflammatory profile in soft tissues and crevicular fluid. PI, PD, and control patients were recruited (n = 62), and soft tissue biopsies were collected during surgery. Crevicular fluid around implant or tooth was collected. The proportions of major immune cell populations in tissues were analyzed by flow cytometry, and the inflammatory profile in tissue and crevicular fluid by a multiplex immunoassay. No significant difference was seen between PI and PD lesions in the proportions of immune cells. PI tissues showed an increased frequency of B cells in comparison with control tissues, along with higher levels of IL-1ß, TNF-α, IL-4, and BAFF in tissue and crevicular fluid. Moreover, TNF-α, IL-17A, and BAFF were higher in PI tissues, but not in PD, than in control tissues. The immune cell composition did not differ significantly between PI and PD, but an enhanced inflammatory profile was seen in PI tissue. PI lesions were enriched in B cells, and displayed increased levels of IL-1ß, TNF-α, IL-4, and BAFF in both tissue and crevicular fluid.

Primary apical periodontitis correlates to elevated levels of interleukin-8 in a Swedish population: A report from the PAROKRANK study.

AIM: To explore associations between root filled teeth, primary and secondary apical periodontitis, and levels of inflammatory markers in blood from patients with a first myocardial infarction and matched controls. METHODOLOGY: Between May 2010 and February 2014, 805 patients with a first myocardial infarction and 805 controls, matched for sex, age, and postal code area, were recruited to the multicentre case-control study PAROKRANK (periodontitis and its relation to coronary artery disease). All participants underwent a physical and oral examination, as well as blood sampling. Using panoramic radiography, root filled teeth, primary apical periodontitis, and secondary apical periodontitis were assessed by three independent observers. Blood samples were analysed with enzyme-linked immunosorbent assay method for the following inflammatory markers: interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-12p70, tumour necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Additionally, white blood cell count and plasma-fibrinogen were analysed. Associations between endodontic variables and the levels of inflammatory markers were statistically analysed with Mann-Whitney U-test and Spearman correlation, adjusted for confounding effects of baseline factors (sex, age, myocardial infarction, current smoking, diabetes, family history of cardiovascular disease, education, marital status, and periodontal disease). RESULTS: Mean age of the cohort was 62 years, and 81% were males. Root fillings were present in 8.4% of the 39 978 examined teeth and were associated with higher levels of hsCRP, fibrinogen, and leukocyte count, but lower levels of IL-2 and IL-12p70. After adjusting for confounders, root filled teeth remained associated with higher levels of fibrinogen, but lower levels of IL-1ß, IL-2, IL-6, and IL-12p70. Primary apical periodontitis was found in 1.2% of non-root filled teeth and associated with higher levels of IL-8 (correlation 0.06, p = .025). Secondary apical periodontitis was found in 29.6% of root filled teeth but did not relate to the levels of any of the inflammatory markers. CONCLUSIONS: This study supports the notion that inflammation at the periapex is more than a local process and that systemic influences cannot be disregarded. Whether the observed alterations in plasma levels of inflammatory markers have any dismal effects on systemic health is presently unknown but, considering the present results, in demand of further investigation.

Association of salivary TREM-1 and PGLYRP1 inflammatory markers with non-communicable diseases.

AIM: Triggering receptor expressed on myeloid cells 1 (TREM-1) and peptidoglycan recognition protein 1 (PGLYRP1) are elevated in biofluids in the presence of various inflammatory conditions. This cross-sectional study aimed to evaluate the effect of age, sex, smoking and different oral and systemic non-communicable diseases on the levels of TREM-1 and PGLYRP1 in saliva. MATERIALS AND METHODS: In total, 445 individuals (mean age 48.7 ± 16.9 years, female:male 51%:49%) were included. All provided self-reported information on smoking and systemic diseases and whole stimulated saliva. Periodontal and cariological parameters were recorded. Salivary levels of TREM-1, PGLYRP1 and total protein were measured using commercially available assays. RESULTS: Salivary TREM-1 levels were significantly higher in stages III-IV periodontitis compared to other periodontal diagnoses (p < .05). Smoking, bleeding on probing (BOP), percentage of pockets ≥4 mm and the number of manifest caries were associated with TREM-1 (p < .05), while sex, BOP, number of manifest caries and muscle and joint diseases were associated with PGLYRP1 (p < .05). CONCLUSIONS: Salivary TREM-1 is associated with periodontitis and caries, while PGLYRP1 is associated with gingival inflammation and caries. Additionally, TREM-1 levels are modified by smoking, while PGLYRP1 is modified by sex and muscle and joint diseases. TREM-1 and PGLYRP1 in saliva could serve as potential biomarkers for detecting and monitoring non-communicable diseases.

Inflammatory markers in saliva and urine reflect disease activity in patients with systemic lupus erythematosus.

BACKGROUND: Laboratory tests of blood and sometimes urine are used to diagnose and to monitor disease activity (DA) in SLE. Clinical practice would be simplified if non-invasive urine and salivary tests could be introduced as alternatives to blood samples. We therefore explored the levels of innate immunity-related biomarkers in matched serum, urine and saliva samples from patients with SLE. METHODS: A total of 84 patients with SLE selected to represent high and low general DA, and 21 controls were included. All participants underwent a thorough clinical examination. General DA and renal DA were measured. The levels of colony-stimulating factor (CSF)-1, interleukin (IL)-34, tumour necrosis factor (TNF)-α, interferon-γ-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, calprotectin, macrophage inflammatory protein (MIP)-1α and MIP-1ß were analysed by immunoassays and related to DA. RESULTS: CSF-1, TNF-α, IP-10 and MCP-1 in saliva, serum and urine, as well as calprotectin in saliva and urine were increased in patients with SLE as compared with controls (p<0.05). TNF-α, IP-10 and MCP-1 in saliva, serum and urine, and CSF-1 in saliva and serum distinguished patients with SLE from controls (area under the curve >0.659; p<0.05 for all). CSF-1 in serum and urine, and calprotectin in saliva and urine, as well as TNF- α, IP-10 and MCP-1 in urine correlated positively with measures of general DA (p<0.05). Patients with SLE with active renal disease presented elevated levels of TNF-α, IP-10 and MCP-1 in urine and CSF-1 and IP-10 in serum as compared with patients with SLE with non-active renal disease. CONCLUSIONS: Our investigation demonstrates that saliva is a novel alternative body fluid, with potential for surveillance of general DA in patients with SLE, but urine is more informative in patients with SLE with predominantly renal DA.

What is the future of Periodontal Medicine?

In the last five decades, considerable progress has been made towards understanding the etiology and pathogenesis of periodontal diseases and their interactions with the host. The impact of an individual periodontal condition on systemic homeostasis became more evident because of this knowledge and prompted advances in studies that associate periodontitis with systemic diseases and conditions. The term Periodontal Medicine describes how periodontal infection/inflammation can affect extraoral health. This review presents the current scientific evidence on the most investigated associations between periodontitis and systemic diseases and conditions, such as cardiovascular diseases, diabetes, preterm birth and low birth weight, and pneumonia. Additionally, other associations between periodontitis and chronic inflammatory bowel disease, colorectal cancer, and Alzheimer's disease that were recently published and are still poorly studied were described. Thus, the aim of this review was to answer the following question: What is the future of Periodontal Medicine? Epidemiological evidence and the evidence of biological plausibility between periodontitis and general health reinforce the rationale that the study of Periodontal Medicine should continue to advance, along with improvements in the epidemiological method, highlighting the statistical power of the studies, the method for data analysis, the case definition of periodontitis, and the type of periodontal therapy to be applied in intervention studies.

Colony-stimulating factor-1 receptor blockade attenuates inflammation in inflamed gingival tissue explants.

BACKGROUND AND OBJECTIVE: Colony-stimulating factor-1 receptor (CSF-1R) regulates myeloid cell function and mediates osteoclastogenesis. CSF-1R blockade has been suggested as a potential therapeutic target to halt inflammation and bone resorption; however, the expression and function of CSF-1R in human gingiva is yet unknown. METHODS: Gingival tissue was collected from 22 non-periodontitis controls and 31 periodontitis (PD) patients. CSF-1R expression in gingival tissue was assessed with q-PCR, western blot, and immunohistochemistry (IHC). Cell surface expression of CSF-1R was analyzed by flow cytometry. The effects of CSF-1R inhibition on the production of inflammatory mediators by inflamed gingival tissue explants and peripheral blood mononuclear cells (PBMCs) were assessed with a bead-based multiplex array and ELISA. RESULTS: CSF-1R protein expression was increased in gingival tissue from PD patients compared with controls as assessed with western blot (1.5-fold increase) and IHC (4.5-fold increase). Similar proportions of HLA-DR+ CD64+ cells and comparable CSF-1R expression in this cell population were found in gingival tissue from PD patients and controls. In peripheral blood monocytes, CSF-1R was predominantly expressed by non-classical and intermediate monocytes. Targeting CSF-1R in gingival tissue explants attenuated the production of MMP-1, MMP-2, MMP-12, and MMP-13. The blocking in PBMCs attenuated the production of IL-8 and MMP-9. CONCLUSION: These results indicate that CSF-1R is elevated in PD, and its inhibition attenuates inflammatory mediators in the inflamed gingival tissue and circulating myeloid cells. Together these findings suggest that CSF-1R might be involved in regulating inflammatory processes in PD, and a potential therapeutic target to reduce the harmful inflammation.

Impact of chronic gingivitis management on the cytokine and anti-PPAD expressions in juvenile systemic lupus erythematosus: A six-month follow-up.

OBJECTIVE: To evaluate how chronic gingivitis treatment impacts the oral and circulating cytokine expressions after six-month follow-up in patients with juvenile systemic lupus erythematosus (jSLE) and also to evaluate the circulating expression of anti-Porphyromonas gingivalis peptidylarginine deiminase antibodies (anti-PPAD) before and after treatment. BACKGROUND: Juvenile systemic lupus erythematosus patients present a worse periodontal condition associated with higher gingival crevicular fluid (GCF) levels of interleukin (IL)-1ß, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon-γ and monocyte chemoattractant protein (MCP)-1. MATERIALS AND METHODS: Twenty-one adolescents with jSLE (mean age: 16.2 ± 1.5 years) were recruited. Participants were rheumatologically and periodontally examined. All individuals were clinically diagnosed with gingival inflammation. Chronic gingivitis treatment consisted of supragingival scaling, prophylaxis and oral hygiene instructions. The cytokine levels were determined by bead-based multiplex assays and the anti-PPAD levels by ELISA. Gingival crevicular fluid (GCF) and serum samples were collected at baseline and 6 months after treatment. RESULTS: We observed a reduction in attachment loss, SLE Disease Activity Index (SLEDAI), IL-1ß, IL-10 and MCP-1 GCF levels, and the IL-4 and IL-5 serum levels 6 months after periodontal treatment. On the contrary, a significant increase in GCF expression of IL-4, IL-12, IL-17, IFN-γ and serum levels of anti-PPAD antibody was observed. CONCLUSION: Juvenile systemic lupus erythematosus patients seem to positively benefit from periodontal treatment by a significantly reduced CAL, a GCF reduction of pro-inflammatory cytokines and an increasing of anti-inflammatory ones. However, an increase in the GCF expression of IL-17 and the serum expression of anti-PPAD antibody 6 months after periodontal treatment might negatively affect the treatment outcome of such patients in the long term.

Levels of myeloid-related proteins in saliva for screening and monitoring of periodontal disease.

AIM: To evaluate the salivary levels of myeloid-related markers in relation to periodontal disease and their potential screening capability, as well as the effects of periodontal treatment on these markers in periodontitis patients. MATERIALS AND METHODS: Participants with a healthy periodontium (n = 60) and with gingivitis (n = 63) and periodontitis (n = 72) were recruited. Periodontitis patients received non-surgical treatment and were re-examined after 3 and 6 months. Unstimulated saliva was collected at baseline and at 1, 3, and 6 months after therapy for the periodontitis patients. Levels of colony-stimulating factor-1 (CSF-1), interleukin-34 (IL-34), S100A8/A9, S100A12, hepatocyte growth factor (HGF), IL-1ß, and matrix metalloproteinase-8 (MMP-8) were analysed by immunoassays. RESULTS: CSF-1, S100A8/A9, S100A12, IL-1ß, MMP-8, and HGF were significantly elevated in saliva from periodontitis and gingivitis patients in comparison to healthy individuals, whereas IL-34 was significantly lower in periodontitis compared to both healthy individuals and gingivitis patients. IL-34 increased significantly 3 months after treatment, while IL-1ß and MMP-8 decreased 1 month after therapy. Additionally, periodontitis patients clustered in high and low levels of S100A8/A9, whereby those with high levels had more bleeding, deeper pockets, and higher S100A12. CONCLUSIONS: Salivary levels of myeloid-related markers are altered in periodontitis and are partially modulated by periodontal treatment. Measuring S100A8/A9 in saliva may identify distinct groups of periodontitis patients.

Periodontitis is associated to increased systemic inflammation in postmyocardial infarction patients.

OBJECTIVE: Periodontitis has been independently associated to cardiovascular disease. However, the biological mechanisms underlying such association are still partially unknown. Thus, this study aimed to discover immunological clues accounting for the increased risk of myocardial infarction (MI) in patients having periodontitis. METHODS: We included 100 patients with a first MI, 50 with and 50 without severe periodontitis, and 100 age-matched, sex-matched and area-matched controls from the Periodontitis and Its Relation to Coronary Artery Disease Study. Participants underwent comprehensive clinical and laboratory examinations 6-10 weeks after the MI and plasma expression of 92 inflammation-related markers was assessed through proximity extension assay. RESULTS: Patients who had an MI displayed altered expression of CCL19, TNFRSF9 and LAP TGF-ß1 in comparison with controls. TNFRSF9 correlated significantly with the amount of alveolar bone loss. MI patients with deep periodontal pockets showed increased white cell count and higher expression of FGF-21, HGF, OSM, CCL20 and IL-18R1 than patients without. White cell count correlated significantly with four of these proteins. CONCLUSIONS: Collectively, our results indicate molecular markers that could be responsible for the increased systemic inflammatory activity in patients with MI with periodontitis.

Peri-implant treatment reduces the salivary levels of Colony stimulator factor-1 and S100A8/A9.

This study evaluated the impact of peri-implant treatment in the salivary levels of Colony stimulator factor -1 (CSF-1), S100A8/A9 and S100A12 in patients having mucositis or peri-implantitis. As a secondary aim, we analysed the correlation between the salivary and peri-implant crevicular fluid (PICF) levels. Forty-seven patient, 27 having mucositis (mean age 63.11 ± 7.78) and 20 having peri-implantitis (61.25 ± 7.01) participated in the study. Clinical parameters, probing pocket depth, clinical attachment level, % of plaque and bleeding on probing were evaluated. Unstimulated whole saliva was collected from all patients, while PICF was collected only from a patient's subgroup (n = 20). Samples were collected before and 3 months after peri-implant treatment. Enzyme-linked immunosorbent assays determined levels of CSF-1, S100A8/A9 and S100A12. Clinical parameters improved and salivary levels of CSF-1 and S100A8/A9, but not S100A12, reduced significantly after treatment in both groups. No significant correlation was found in the salivary and PICF levels of the same molecule. In conclusion, the treatment of peri-implant disease significantly improved the clinical parameters and reduced the salivary levels of CSF-1 and S100A8/A9. The salivary expressions of CSF-1, S100A8/A9 and S100A12 did not correlate with their own expression in PICF.

What is the future of Periodontal Medicine?

Abstract In the last five decades, considerable progress has been made towards understanding the etiology and pathogenesis of periodontal diseases and their interactions with the host. The impact of an individual periodontal condition on systemic homeostasis became more evident because of this knowledge and prompted advances in studies that associate periodontitis with systemic diseases and conditions. The term Periodontal Medicine describes how periodontal infection/inflammation can affect extraoral health. This review presents the current scientific evidence on the most investigated associations between periodontitis and systemic diseases and conditions, such as cardiovascular diseases, diabetes, preterm birth and low birth weight, and pneumonia. Additionally, other associations between periodontitis and chronic inflammatory bowel disease, colorectal cancer, and Alzheimer's disease that were recently published and are still poorly studied were described. Thus, the aim of this review was to answer the following question: What is the future of Periodontal Medicine? Epidemiological evidence and the evidence of biological plausibility between periodontitis and general health reinforce the rationale that the study of Periodontal Medicine should continue to advance, along with improvements in the epidemiological method, highlighting the statistical power of the studies, the method for data analysis, the case definition of periodontitis, and the type of periodontal therapy to be applied in intervention studies.

Adjunctive Antiseptic Irrigation of Periodontal Pockets: Effects on Microbial and Cytokine Profiles.

To evaluate the effect of adjunctive antiseptic irrigation of periodontal pockets on microbial and cytokine profiles. Fifty-nine patients with severe periodontitis were allocated to one of three groups for scaling and root planing facilitated with different adjunctive antiseptics: 1% polyhexamethyleneguanidine phosphate (PHMG-P) (n = 19), 0.2% chlorhexidine (CHX) (n = 21) or distilled water (n = 19). Gingival crevicular fluid and subgingival bacterial samples were collected at baseline, and at 2 weeks, and 1 and 4 months. The levels of interleukin (IL)-1ß, IL-8, IL-10, and IL-17A, matrix metalloproteinase (MMP)-8, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum,Aggregatibacter actinomycetemcomitans, and Prevotella intermedia were determined. There were no intergroup differences in cytokine concentrations and bacterial counts at any follow-up, however, varying patterns were observed. In the PHMG-P and water groups IL-1ß expression peaked at 2 weeks and then gradually declined. In all three groups, the dynamics of MMP-8 concentration were non-linear, increasing by 2 weeks and then declining to below baseline (p > 0.05). P. gingivalis and T. forsythia declined within the first month and increased thereafter, not regaining the baseline level. Adjunctive antiseptic treatment was associated with changes in biomarkers and bacterial counts in the course of the study. The effects of adjunctive antiseptic irrigation were limited in the applied protocol.

Salivary and Serum Inflammatory Profiles Reflect Different Aspects of Inflammatory Bowel Disease Activity.

BACKGROUND: Inflammatory bowel disease (IBD) can manifest both macroscopically and microscopically in the oral cavity; however, little is known about salivary changes in IBD. Therefore, this study aimed to assess salivary and circulatory inflammatory profiles in IBD and to compare their potential to reflect the presence and activity of IBD. METHODS: We measured 92 known inflammatory proteins in serum and in unstimulated and stimulated whole saliva samples from patients with IBD with active intestinal inflammation (n = 21) and matched control patients (n = 22) by proximity extension assay. Fifteen of the patients with IBD returned 10 to 12 weeks after treatment escalation for resampling. RESULTS: Sixty-seven of the proteins were detected in all 3 sample fluids but formed distinct clusters in serum and saliva. Twenty-one inflammatory proteins were significantly increased and 4 were significantly decreased in the serum of patients with IBD compared with that of the control patients. Two of the increased serum proteins, IL-6 and MMP-10, were also significantly increased in stimulated saliva of patients with IBD and correlated positively to their expressions in serum. None of the investigated proteins in serum or saliva were significantly altered by IBD treatment at follow-up. Overall, inflammatory proteins in serum correlated to biochemical status, and salivary proteins correlated positively to clinical parameters reflecting disease activity. CONCLUSIONS: Saliva and serum inflammatory profiles in IBD share a similar composition but reflect different aspects of disease activity. The oral cavity reflects IBD through elevated IL-6 and MMP-10 in stimulated saliva.

Periodontal disease and its impact on general health in Latin America. Section V: Treatment of periodontitis.

Gingivitis and periodontitis are associated with a negative impact on Oral Health Related Quality of Life (OHRQoL), exerting a significant influence on aspects related to the patients' function and esthetics. Periodontitis has been associated with several systemic conditions, including adverse pregnancy outcomes, cardiovascular diseases, type 2 diabetes mellitus (DM), respiratory disorders, fatal pneumonia in hemodialysis patients, chronic renal disease and metabolic syndrome. The aim of this paper was to review the results of different periodontal treatments and their impacts on patients' OHRQoL and systemic health. Non-surgical and surgical periodontal treatments are predictable procedures in terms of controlling infection, reducing probing pocket depth and gaining clinical attachment. In addition, the treatment of periodontitis may significantly improve OHRQoL and promote a reduction in the levels of systemic markers of inflammation, including some cytokines associated with cardiovascular diseases. Studies have also suggested that periodontal treatment may improve glycemic control in patients with DM. Strategies and actions for preventing the onset and recurrence of periodontitis, and the challenges facing the field of periodontology in the XXI century are presented in this review.

S100A12 Expression Is Modulated During Monocyte Differentiation and Reflects Periodontitis Severity.

S100A12 is a calcium-binding protein of the S100 subfamily of myeloid-related proteins that acts as an alarmin to induce a pro-inflammatory innate immune response. It has been linked to several chronic inflammatory diseases, however its role in the common oral immunopathology periodontitis is largely unknown. Previous in vitro monoculture experiments indicate that S100A12 production decreases during monocyte differentiation stages, while the regulation within tissue is poorly defined. This study evaluated S100A12 expression in monocyte subsets, during monocyte-to-macrophage differentiation and following polarization, both in monoculture and in a tissue context, utilizing a three-dimensional co-culture oral tissue model. Further, we explored the involvement of S100A12 in periodontitis by analyzing its expression in peripheral circulation and gingival tissue, as well as in saliva. We found that S100A12 expression was higher in classical than in non-classical monocytes. S100A12 expression and protein secretion declined significantly during monocyte-to-macrophage differentiation, while polarization of monocyte-derived macrophages had no effect on either. Peripheral monocytes from periodontitis patients had higher S100A12 expression than monocytes from controls, a difference particularly observed in the intermediate and non-classical monocyte subsets. Further, monocytes from periodontitis patients displayed an increased secretion of S100A12 compared with monocytes from controls. In oral tissue cultures, monocyte differentiation resulted in increased S100A12 secretion over time, which further increased after inflammatory stimuli. Likewise, S100A12 expression was higher in gingival tissue from periodontitis patients where monocyte-derived cells exhibited higher expression of S100A12 in comparison to non-periodontitis tissue. In line with our findings, patients with severe periodontitis had significantly higher levels of S100A12 in saliva compared to non-periodontitis patients, and the levels correlated to clinical periodontal parameters. Taken together, S100A12 is predominantly secreted by monocytes rather than by monocyte-derived cells. Moreover, S100A12 is increased in inflamed tissue cultures, potentially as a result of enhanced production by monocyte-derived cells. This study implicates the involvement of S100A12 in periodontitis pathogenesis, as evidenced by increased S100A12 expression in inflamed gingival tissue, which may be due to altered circulatory monocytes in periodontitis.

CSF-1 and IL-34 levels in peri-implant crevicular fluid and saliva from patients having peri-implant diseases.

OBJECTIVE: Colony-stimulating factor (CSF)-1 and interleukin (IL)-34 are growth factors that regulate myeloid cell functions and support osteoclastogenesis. CSF-1 and IL-34 levels in peri-implant diseases are yet unknown. This study evaluated CSF-1, IL-34, and IL-1ß levels in saliva and peri-implant crevicular fluid (PICF) from patients having mucositis or peri-implantitis, as well as their correlation to clinical parameters of disease. MATERIAL AND METHODS: Forty-three patients were included (mean age 61.1 ± 8.4; 62.8% female), 20 having mucositis and 23 having peri-implantitis. Patients were clinically examined and unstimulated whole saliva and PICF were collected. Levels of CSF-1, IL-34, and IL-1ß were determined by enzyme-linked immunosorbent assays. RESULTS: CSF-1 levels were higher in PICF from peri-implantitis compared with mucositis patients (p = 0.028), whereas IL-34 levels showed no significant difference between the groups (p = 0.060). No significant difference was found in PICF IL-1ß levels between the groups. Salivary levels of CSF-1 and IL-34 did not differ significantly between mucositis and peri-implantitis. No significant difference was observed in the salivary levels of IL-1ß between groups (p = 0.061). CSF-1 and IL-1ß correlated significantly in both saliva and PICF. CSF-1 levels in saliva correlated with its levels in PICF. PICF CSF-1 levels showed potential to discriminate between peri-implantitis and mucositis (AUC = 0.695, 95% CI 0.53-0.85; p = 0.029). CONCLUSION: Increased levels of CSF-1 in peri-implant crevicular fluid, but not in saliva, were found in peri-implantitis patients, which might aid to discriminate the early and late stages of peri-implant diseases. CLINICAL RELEVANCE: This result suggests an increased osteoclastogenic potential in peri-implantitis patients.

The modulation of the TREM-1/PGLYRP1/MMP-8 axis in peri-implant diseases.

OBJECTIVES: The aim of this study is to investigate the expression of sTREM-1 and its ligand PGLYRP1, as well as the expression of MMP-8 and its inhibitor TIMP-1, in peri-implant diseases. As a secondary aim, we analyzed the influence of the concomitant existence of periodontitis in the expression of these biomarkers. MATERIALS AND METHODS: This study included 77 patients (29 males and 48 females; mean age 55.0 ± 11.5), 18 having gingivitis, 16 having periodontitis, 20 having mucositis, and 23 having peri-implantitis. Patients were clinically examined, and unstimulated whole saliva was collected. sTREM-1, PGLYRP1, MMP-8, TIMP-1, and MMP-8/TIMP1 ratio were determined by ELISA. RESULTS: The periodontitis group presented higher probing depth (PD) mean, and higher clinical attachment loss, compared with the other groups. The peri-implantitis group presented higher PD mean in implants compared to the mucositis group. Patients with PD ≥ 6 mm showed significantly higher levels of PGLYRP1, MMP-8, and MMP-8/TIMP-1 ratio than patients with PD < 6 mm. When all four markers were assessed, there were no significant differences between mucositis and peri-implantitis groups. Concomitant periodontitis resulted in higher significant levels of MMP-8 in patients with peri-implant disease. CONCLUSION: We did not observe significant differences in the levels of the sTREM-1/PGLYRP1/MMP-8 axis between patients with periodontal and peri-implant diseases, suggesting that these markers are also involved in the inflammatory process around implants. Besides, the presence of periodontitis may affect the levels of MMP-8 in patients with peri-implant disease. CLINICAL RELEVANCE: The sTREM-1/PGLYRP1/MMP-8 axis could be useful as potent markers in periodontal and peri-implant diseases.

Periodontal disease and its impact on general health in Latin America. Section V: Treatment of periodontitis

Abstract: Gingivitis and periodontitis are associated with a negative impact on Oral Health Related Quality of Life (OHRQoL), exerting a significant influence on aspects related to the patients' function and esthetics. Periodontitis has been associated with several systemic conditions, including adverse pregnancy outcomes, cardiovascular diseases, type 2 diabetes mellitus (DM), respiratory disorders, fatal pneumonia in hemodialysis patients, chronic renal disease and metabolic syndrome. The aim of this paper was to review the results of different periodontal treatments and their impacts on patients' OHRQoL and systemic health. Non-surgical and surgical periodontal treatments are predictable procedures in terms of controlling infection, reducing probing pocket depth and gaining clinical attachment. In addition, the treatment of periodontitis may significantly improve OHRQoL and promote a reduction in the levels of systemic markers of inflammation, including some cytokines associated with cardiovascular diseases. Studies have also suggested that periodontal treatment may improve glycemic control in patients with DM. Strategies and actions for preventing the onset and recurrence of periodontitis, and the challenges facing the field of periodontology in the XXI century are presented in this review.