Salivary IL-6 Research Articles

Salivary Interleukin Levels in Oral Squamous Cell Carcinoma and Oral Epithelial Dysplasia: Findings from a Sri Lankan Study.

The incidence of oral squamous cell carcinoma (OSCC), and its precursor, oral epithelial dysplasia (OED), is on the rise, especially in South Asia. OSCC is the leading cancer in males in Sri Lanka, with >80% diagnosed at advanced clinical stages. Early detection is paramount to improve patient outcome, and saliva testing is a promising non-invasive tool. The aim of this study was to assess salivary interleukins (lL1β, IL6, and IL8) in OSCC, OED and disease-free controls in a Sri Lankan study cohort. A case-control study with OSCC (n = 37), OED (n = 30) patients and disease-free controls (n = 30) was conducted. Salivary lL1β, IL6, and IL8 were quantified using enzyme-linked immuno-sorbent assay. Comparisons between different diagnostic groups and potential correlations to risk factors were assessed. Salivary levels for the three tested interleukins increased from disease-free controls through OED, and were highest in OSCC samples. Furthermore, the levels of IL1β, IL6, and IL8 increased progressively with OED grade. The discrimination between patients (OSCC and OED) and controls, as assessed by AUC of receiver operating characteristic curves, was 0.9 for IL8 (p = 0.0001) and 0.8 for IL6 (p = 0.0001), while IL1β differentiated OSCC from controls (AUC 0.7, p = 0.006). No significant associations were found between salivary interleukin levels and smoking, alcohol, and betel quid risk factors. Our findings suggest that salivary IL1β, IL6, and IL8 are associated with disease severity of OED, and are potential biomarkers for predicting disease progression in OED, and the screening of OSCC.

Effects of a Physical Activity Program in Psychobiological Profile of Individuals with Schizophrenia

The purposes of the present study were to verify the therapeutic effects of a Physical Activity Program (PAP) in individuals with schizophrenia from public mental health care services of São Paulo; compare levels of depression, trait and state anxiety, mood and levels of pro-inflammatory components of the immune system (Interleukin-6, IL-6) and Tumor Necrosis Factor -alpha (TNF-alpha)). A PAP was performed for 12 weeks, twice a week, ~45 minutes each session and aerobic emphasis. 32 individuals diagnosed with schizophrenia (15 females and 17 males) were divided into Control Group (CG, n=11, did not participate in the PAP); Intermediate Group (IG, n=10, performed less than 70% of sessions) and Exercise Group (EG, n=11, performed more than 70% of sessions). Anamnesis, anthropometry, and the following assessments were applied before and after the PAP: Beck Depression Index (BDI), State-Trait Anxiety Inventory (STAI), Brunels Mood Scale (BRUMS), and levels of salivary IL-6 and TNF-alpha. After the PAP, there were no significant anthropometric changes in any of the groups. There was a statistically significant reduction (p<0.05) within the EG for the variables BDI (p=0.008), STAI-Trait (p=0.040), sub variable “depression” of the BRUMS (p=0.036), and IL-6 (p=0.028) level. It is concluded that the implementation of a simple PAP was able to promote favorable therapeutic effects in the participants, regardless of anthropometric changes.

Diagnostic potential of salivary interleukin-17, RANKL, and OPG to differentiate between periodontal health and disease and discriminate stable and unstable periodontitis: A case-control study.

Limitations of the conventional diagnostic techniques urged researchers to seek novel methods to predict, diagnose, and monitor periodontal disease. Use of the biomarkers available in oral fluids could be a revolutionary surrogate for the manual probing/diagnostic radiograph. Several salivary biomarkers have the potential to accurately discriminate periodontal health and disease. This study aimed to determine the diagnostic sensitivity and specificity of salivary interleukin (IL)-17, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), RANKL/OPG for differentiating (1) periodontal health from disease and (2) stable and unstable periodontitis. Participants with periodontitis (n = 50) and gingivitis (n = 25), both diseases represented the cases, and subjects with healthy periodontium (n = 15) as a control were recruited for this study. Periodontitis cases were further equally subdivided into stable and unstable. Whole unstimulated salivary sample were collected from all participants. Periodontal parameters including bleeding on probing, probing pocket depth, clinical attachment loss, and number of missing teeth were recorded. The protein levels of salivary IL-17, RANKL, and OPG were determined by using enzyme-linked immunosorbent assays technique. Salivary IL-17, OPG, RANKL, and RANKL/OPG showed high sensitivity and specificity to differentiate periodontal health from gingivitis and periodontitis. Similar pattern was observed in discriminating stable and unstable periodontitis. Salivary IL-17 and RANKL showed a good accuracy to differentiate gingivitis from periodontitis. However, OPG and RANKL/OPG did not exhibit enough sensitivity and specificity to differentiate the latter conditions. Salivary IL-17, RANKL, OPG, and RANKL/OPG system are potential candidates for differentiating periodontal health and disease and discriminate stable and unstable periodontitis.

Assessment of salivary and gingival crevicular fluids IL6, IL-8, IL-12, and IL-17 levels in healthy subjects and patients with periodontal disease.

Biomarkers present in the oral fluid (saliva and GCF) have been studied thoroughly in order to be used as adjuncts to the diagnosis of periodontal disease. In periodontal diseases, inflammatory mediators, including IL6, IL-8, IL-12, and IL-17, may promote the degeneration of periodontal tissues. The aim of the present study was to quantify IL6, IL-8, IL-12, and IL-17 levels in the saliva and GCF for patients with generalized periodontitis and compare it with healthy subjects. Furthermore, identifying the most reliable biofluids (saliva and GCF) that can be utilized for biomarkers detection in periodontitis patients. In this study, GCF and saliva samples were collected from 40 patients with generalized periodontitis and 20 healthy subjects. Enzyme-linked immune absorbent assay (ELISA) was used in the measurement of interleukin levels. The mean levels of IL6, IL-8, IL-12, and IL-17 either in saliva or GCF were higher in periodontitis patients than in healthy subjects. These results suggest that the levels of IL6, IL-8, IL-12, and IL-17 in GCF or saliva may be relevant in the pathophysiology of periodontitis, and the measurement of these cytokines may be beneficial in the identification of patients with periodontitis. Furthermore, some biomarkers for periodontal disease are detected better in saliva, while others are best detected in GCF.

SPECIFIC FEATURES OF THE ORAL MICROBIOME IN YOUNG CHILDREN WITH ARYNGOPHARYNGEAL REFLUX AND ITS ROLE THE DEVELOPMENT OF RECURRENT RESPIRATORY DISEASES.

The aim: To examine the composition of the oral microbiome in young children with laryngopharyngeal reflux (LPR) and its role the development of recurrent respiratory diseases. Materials and methods: There were examined 38 children with physiological gastroesophageal reflux (GER), 18 children with LPR who had a medical history of recurrent bronchitis and 17 healthy children (control group). The study included the collection of anamnesis, objective examination. The qualitative and quantitative microbial composition of the upper respiratory tract was performed obtained by oropharyngeal deep swab. Salivary pepsin level and IL-8 were determined by enzyme-linked immunosorbent assay. Results: This research showed significant alterations in the oral microbiome of patients with GER and LPR as compared to healthy control. We found that gram-negative microbiota such as Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris, Proteus spp. and Candida albicans were identified in children with GER and LPR compared to the healthy control. At the same time, the amount of such a representative of the normal microbiome as Streptococcus viridans in children with LPR was sharply reduced. There were established a much higher mean salivary pepsin level of the patients with LPR than in the GER and control group. We found the association between high pepsin levels, saliva IL-8 levels and frequency of respiratory pathology in children with LPR. Conclusions: Our study confirms that increased levels of pepsin in saliva are a risk factor for recurrent respiratory diseases in children with LPR.

THE PROGNOSTIC SIGNIFICANCE OF SALIVARY PEPSIN LEVEL IN THE DEVELOPMENT OF RECURRENT RESPIRATORY PATHOLOGY IN INFANTS WITH RUMINATION SYNDROME

Introduction. Infant rumination syndrome (IRS) is most common among infants with functional disorders of the gastrointestinal tract and can lead to the development of recurrent respiratory pathology. Pepsin is believed to play a key role in the upper airway mucosa impairment. The objective of the study was to determine the prognostic significance of salivary pepsin level in the development of recurrent respiratory pathology in infants with rumination syndrome. Materials and Methods. We analyzed the clinical and anamnestic data of 55 infants: the main group consisted of 38 children with apparent rumination syndrome, and the comparison group included 17 healthy children with no clinical manifestations of this syndrome. Salivary pepsin and IL-8 levels were measured three times a day by the enzyme-linked immunosorbent assay (Human Pepsin Elisa Kit and Human IL-8 ELISA Kit, USA). The study results were statistically processed using the Statistica v.6.1 software package. To assess the diagnostic significance of salivary pepsin level, ROC analysis was performed to determine the optimal cut-off point and calculate the area under the ROC curve (AUC) with 95% CI and operating characteristics of the criterion (sensitivity and specificity). Results and Discussion. Daily monitoring of salivary pepsin in infants showed that pepsin level was significantly higher in the main group vs. the comparison group, both for average daily values and intermediate indicators. No statistically significant difference was found between the three saliva samples and the daily average pepsin level in the main group of infants, which may be indicative of latent episodes of reflux during the day. A direct correlation was found between salivary levels of IL-8 and pepsin levels in the main group of children (r = 0.78, p < 0.05). Among the potential predictors of recurrent respiratory pathology risk in infants with rumination syndrome, the following were established: fasting pepsin level > 309.27 pg/ml, pepsin level in 1 hour after feeding > 275.73 pg/ml, and pepsin level after regurgitation > 532.31 pg/ml. Conclusions. Fasting pepsin level > 309.27 pg/ml and pepsin level in 1 hour after feeding > 275.73 pg/ml can be used in a multiple logistic regression model to predict the risk of recurrent respiratory pathology, taking into account other clinical, anamnestic, and laboratory data. A post-regurgitation pepsin level > 532.31 pg/ml is an independent predictor and can be used alone.

Extracellular Vesicles from Carcinoma-associated Fibroblasts Promote EMT of Salivary Adenoid Cystic Carcinoma Via IL-6

Carcinoma-associated fibroblasts (CAFs) play a pivotal role in cancer progression. Salivary adenoid cystic carcinoma (SACC) has a high tendency to invade and metastasize. Understanding how CAFs interact with SACC cells is essential for developing new targeted therapies for SACC. Extracellular vesicles (EVs) play important roles in intercellular communication. However, the role of CAFs-derived EVs in SACC invasion remains poorly understood. To show that CAFs EVs are involved in the EMT of SACC and promote tumor invasion. CAFs-derived EVs were characterized by western blot and transmission electron microscopy. Wound healing and transwell assay were performed for assessing biological foundation of CAFs-EVs for tumor cells. RNA interference transfection, western blot, wound healing and transwell assay were applied to study the effect of IL6 from CAFs-EVs on SACC cells and the mechanism. A subcutaneous xenograft model was used to evaluate the EMT of SACC induced by CAFs in vivo. In this study, we show that CAFs EVs promote the migration and invasion of SACC cells. The expression of biomarkers of epithelial-mesenchymal transition (EMT) was higher in SACC cells treated with CAFs EVs than in the negative controls, and high levels of IL6 were detected in CAFs and their EVs. Knockdown of IL6 in CAFs decreased tissue invasiveness and EMT biomarker expression in SACC cells induced by CAFs EVs. CAFs EV-associated IL6 promoted SACC EMT by activating the JAK2/STAT3 signaling pathway. CAFs-derived EVs carry IL6 to improve EMT of SACC by activating the JAK2/STAT3 signaling pathway.

Chronotype and Social Jetlag Influence Performance and Injury during Reserve Officers' Training Corps Physical Training.

Sleep and circadian rhythms are critically important for optimal physical performance and maintaining health during training. Chronotype and altered sleep may modulate the response to exercise training, especially when performed at specific times/days, which may contribute to musculoskeletal injury. The purpose of this study was to determine if cadet characteristics (chronotype, sleep duration, and social jetlag) were associated with injury incidence and inflammation during physical training. Reserve Officers’ Training Corps (ROTC) cadets (n = 42) completed the Morningness/Eveningness Questionnaire to determine chronotype, and 1-week sleep logs to determine sleep duration and social jetlag. Salivary IL-6 was measured before and after the first and fourth exercise sessions during training. Prospective injury incidence was monitored over 14 weeks of training, and Army Physical Fitness Test scores were recorded at the conclusion. Chronotype, sleep duration, and social jetlag were assessed as independent factors impacting IL-6, injury incidence, and APFT scores using ANOVAs, chi-squared tests, and the t-test where appropriate, with significance accepted at p < 0.05. Evening chronotypes performed worse on the APFT (evening = 103.8 ± 59.8 vs. intermediate = 221.9 ± 40.3 vs. morning = 216.6 ± 43.6; p < 0.05), with no difference in injury incidence. Sleep duration did not significantly impact APFT score or injury incidence. Social jetlag was significantly higher in injured vs. uninjured cadets (2:40 ± 1:03 vs. 1:32 ± 55, p < 0.05). Exercise increased salivary IL-6, with no significant effects of chronotype, sleep duration, or social jetlag. Evening chronotypes and cadets with social jetlag display hampered performance during morning APFT. Social jetlag may be a behavioral biomarker for musculoskeletal injury risk, which requires further investigation.

Evaluation of serum and salivary PCSK9 and IL6 and its association with periodontal inflammation and atherosclerotic cardiovascular diseases.

and Purpose: The aim of this study was to assess, compare and correlate the ability of PCSK9 and IL6 as potential common serum and salivary biomarkers for stage III/IV periodontitis and the risk of developing atherosclerotic cardiovascular diseases. 76 patients were alloted into 4 groups consisting of subjects with clinically healthy periodontium and stage III/IV periodontitis with and without ACVD. Clinical parameters - PD, CAL, number of teeth, PI, mSBI, TC, Tg, HDL and LDL were recorded. Serum and saliva samples were obtained and subjected to ELISA for quantifying the biomarker levels. The level of these biomarkers was found to be the lowest (IL6 Serum: 21.92±14.54, IL6 Saliva: 12.34±7.72, PCSK9 Serum: 178.82±35.07, PCSK9 Saliva: 80.82±25.43) in group I and highest in group IV (IL6 Serum: 73.4±24.86, IL6 Saliva: 37.66±15.77, PCSK9 Serum: 346.54±45.11, PCSK9 Saliva: 157.72±43.28). The clinical parameters PI, mSBI, PPD, CAL, total number of teeth, TC, HDL and LDL showed a significant correlation with biomarkers PCSK9 and IL6. This study features the elevation of serum and salivary PCSK9 and IL6 in periodontitis and ACVD. A triad of serum and salivary PCSK9 and IL6 along with the clinical markers of periodontal disease can relatively predict the future risk of developing ACVD.

Salivary concentrations of IL-8 and IL-1ra after HIIT and MICT in young, healthy adults: A randomized exercise study

The purpose of this study was to determine whether six weeks of high intensity interval training (HIIT) would lead to greater changes in resting concentrations of salivary IL-8 and IL-1ra than moderate intensity continuous training (MICT) in young, healthy adults, and to determine whether changes in IL-8 and IL-1ra after six weeks of either HIIT or MICT were associated with changes in maximal exercise capacity (VO2max). Participants were randomly assigned to 6 weeks of HIIT (n = 12) or MICT (n = 11), matched for workload. Saliva samples were collected at the beginning (T1) and end (T2) of the intervention, and analyzed for IL-8 and IL-1ra. Participants in both groups had significant improvements in VO2max; there were no group differences in improvements. A greater reduction in IL-8 was observed in the MICT group when compared to the HIIT group (HIIT median: −9.5; MICT median: −82.3 pg/µg of protein; U = 11.5, p < 0.001). When combining the HIIT and MICT group, there were significant reductions in IL-8 from T1 to T2. There was no correlation between changes in IL-8 (r < 0.00) or IL-1ra (r = −0.013) with changes in VO2max. In conclusion, 6 weeks of exercise training leads to a reduction in IL-8; MICT may lead to greater reductions when compared to HIIT. Future research examining longer intervention periods is needed to further elucidate the effects of HIIT and MICT on different pro and anti-inflammatory cytokines.

Assessment of salivary immunoglobulin A, interleu-kin-6 and C-reactive protein in chronic kidney dis-ease patients on hemodialysis and on conservative treatment

Background: Chronic kidney disease is a gradual loss of kidney function with diabetes and hypertension as the leading cause. Chronic kidney disease is one of these systemic diseases that can affect salivary contents. Aims: This study aimed to assess salivary immunoglobulin A, interleukin-6 and C- reactive protein in chronic kidney disease patients on hemodialysis and those on conservative treatment in comparison with control subjects. Materials and methods: Ninety subjects were included in this study divided into three groups: 30 patients with chronic kidney disease on hemodialysis for at least 6 months ago; 30 patients with chronic kidney disease on conservative treatment and 30 healthy control subjects. Secretory immunoglobulin A, interleukin-6 and C- reactive protein in saliva samples were measured by enzyme-linked immunosorbent assay ELISA. Results: No significant difference in salivary immunoglobulin A level among study groups was seen. A significant increase in salivary interleukin-6 and C- reactive protein in both chronic kidney disease patients on hemodialysis and those on conservative treatment compared to the control group. While, no significant salivary IL-6 and CRP differences were seen between both patient groups, on hemodialysis and conservative treatment. Conclusions: There was no significant difference among chronic kidney disease patients on hemodialysis, on conservative treatment and control healthy subjects regarding to salivary IgA while Salivary interleukin -6 and C- reactive protein was significantly higher in chronic kidney disease patients on hemodialysis and those on conservative treatment compared to healthy subjects.

Influence of periodontal inflammation on tryptophan-kynurenine metabolism: a cross-sectional study.

Kynurenine pathway (KP) is the primary way of degrading tryptophan (TRP) and generates several bioactive metabolites (such as kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3OHKYN)) to regulate biological processes that include host-microbiome signaling and immune cell response. This study is aimed to determine the relationship between periodontal inflammation and tryptophan-kynurenine metabolism and identify their association with periodontal clinical parameters. Saliva and serum samples were collected from 20 stage III, grade B generalized periodontitis patients, and 20 periodontally healthy control individuals. Samples were analyzed for IL-6, KYN, TRP, KYN/TRP ratio, KYNA, 3OHKYN, picolinic acid (PA), and quinolinic acid (QA) by liquid chromatography-mass spectrometry. Clinical periodontal parameters (plaque index (PI), probing pocket depth (PPD), gingival recession (GR), clinical attachment loss (CAL), and bleeding on probing (BOP)) were recorded. Clinical parameters were significantly higher in the periodontitis group (p < 0.001). Salivary IL-6, TRP, KYN, KYNA, PA, and QA levels were significantly higher and KYN/TRP ratio was significantly lower in periodontitis group than control group (p < 0.05). Serum KYN, KYN/TRP ratio and PA levels were significantly higher in periodontitis group than control group (p < 0.05). PPD, BOP, PI, and CAL had significantly positive correlations with salivary IL-6, TRP, PA, QA, and serum KYN and significantly negative correlations with salivary KYN/TRP ratio. Our results suggest that periodontal inflammation plays a role in local and systemic tryptophan-kynurenine metabolism. Due to their effects on the immune and inflammatory systems, kynurenines may be potential agents for diagnosis and treatment of periodontal diseases.

Salivary inflammatory mediators as biomarkers for oral mucositis and oral mucosal dryness in cancer patients: A pilot study.

Oral mucositis (OM) is a common side effect in patients with cancer receiving chemotherapy and radiotherapy; however, no salivary mediator is known to be associated with OM. We aimed to determine candidate salivary inflammatory mediators potentially associated with OM in patients with cancer. To this end, we compared the relationships between OM grade, oral mucosal dryness, and inflammatory mediators (Interleukin (IL)-1β, IL-6, IL-10, IL-12p70, tumor necrosis factor (TNF), prostaglandin E2, and vascular endothelial growth factor) in patients with cancer and in healthy volunteers (HV). We collected saliva samples from 18 patients with cancer according to the following schedule: 1) within 14 days of treatment initiation, 2) within 3 days of OM occurrence, 3) when OM was improved or got worsened, and 4) within 7 days after chemotherapy completion. The oral care support team determined the OM grade at each sample collection point based on CTCAE version 5.0. Salivary inflammatory mediator concentrations were detected using cytometric bead array or enzyme-linked immunoassay. We compared oral mucosal dryness in pre- and post-index patients with cancer to that in HV (n = 33) using an oral moisture-checking device. Fourteen of eighteen patients experienced OM (four, grade 3 OM; four, grade 2 OM; six, grade 1 OM). IL-6, IL-10, and TNF salivary concentrations were significantly increased in the post-index group compared to those in the pre-index group (p = 0.0002, p = 0.0364, and p = 0.0160, respectively). Additionally, salivary IL-6, IL-10, and TNF levels were significantly higher in the post-index group than in the HV group (p < 0.0001, p < 0.05, and p < 0.05, respectively). Significant positive correlations were observed between OM grade and salivary IL-6, IL-10, and TNF levels (p = 0.0004, r = 0.4939; p = 0.0171, r = 0.3394; and p = 0007, r = 0.4662, respectively). Oral mucosal dryness was significantly higher in the HV than in the pre- and post-index groups (p < 0.001). Our findings suggest that salivary IL-6, IL-10, and TNF levels may be used as biomarkers for OM occurrence and grade in patients with cancer. Furthermore, monitoring oral mucosal dryness and managing oral hygiene before cancer treatment is essential.

To compare the levels of salivary Interleukin 6 between oral potentially malignant disorders and oral squamous cell carcinoma

To compare the levels of salivary Interleukin 6 between oral potentially malignant disorders and oral squamous cell carcinoma. After ethical clearance and informed consent, the saliva samples were collected from 20 patients of OPMD’S, 20 patients of OSCC and 10 controls. Salivary IL-6 levels were detected by enzyme linked Immunosorbent essay and appropriate statistical analysis was done. Significant differences in IL-6 concentration between OSCC, OPMD’S and controls were noted. Salivary IL-6 levels were higher in OSCC. The results of present study concluded that the level of salivary IL-6 in OSCC is significantly higher than oral potentially malignant disorders like OSMF and oral epithelial dysplasia and controls. This biomarker can be utilized as a major asset for early detection of cancer and can open a new horizon for treatment plans of targeted therapy.

The effect of Caries, Periodontitis and Substance abuse on Salivary Interleukin - 6 levels

Objective: Earlystage diagnosis of oral cancer will help in complete control of the progression of the lesion.Salivary biomarker analysis is a non-invasive and inexpensive method in the early detection of oral cancer. Materials and Methods: The study aimed at the detection of the changes of salivary IL-6 in caries, periodontitis and substance abuse. Sociodemographic details, habits like tobacco and alcohol abuse were recorded. Clinical factors like caries and periodontal status of subjects were assessed using dentition status and treatment need index and modified CPITN index, respectively. Whole unstimulated saliva was collected and IL-6 estimated using ELISA. Mann Whitney U test was used to compare between clinical groups and demographic variables using ANOVA. Result:The median and mean baseline salivary IL-6 value of the 48 samples were 4.13 and 5.998 ±2.76 pg/ml. Subjects with substance abuse had highest median: 6.82 pg/ml (IQR: 4.871-13.110) and mean values:15.073 ±15.47pg/ml. The median of other groups,caries- 3.53, periodontitis- 4.2 and normal- 4.0, pg/ml respectively. ROC analysis showed AUC for the substance abuse and normal was 78 (sensitivity 71% specificity 82%) substance abuse and all groups was 75 (sensitivity 86% specificity 61%). The cut off was 6.41and 4.2 pg/ml respectively. Conclusion: Based on the higher AUC value, salivary IL-6 levels of more than 6.41pg/ml can be taken as cutoff for clinical evaluation with higher potential for malignant change. The fact that cases with periodontitis did not show a statistically significant difference in IL-6 levels when compared to substance abuse, needs further consideration. Key words: Caries, Interleukin-6, Periodontitis, Salivary biomarkers, Substance abuse.

Salivary IL-6 Concentration Is Associated with Frailty Syndrome in Older Individuals.

Background: One of the physiological changes that is most closely associated with frailty is the increase in pro-inflammatory cytokines, and IL-6 in particular. Most studies have demonstrated this association using blood samples. We analyzed the relationship between frailty syndrome, individual frailty criteria, and IL-6 levels obtained by saliva tests. Methods: A cross-sectional pilot study was performed among women institutionalized in nursing homes. Frailty was defined as having three or more of the following components: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those components. Results: There was a significant and positive correlation between the frailty score and salivary IL-6 concentration. Regarding the associations between IL-6 and individual dichotomized frailty criteria, there were significant differences in salivary IL-6 concentration in two frailty criteria: weight loss (p = 0.002) and low physical activity (p = 0.007). Receiver operating characteristic curve analysis showed that IL-6 concentration significantly (p < 0.05) (although moderately) discriminated patients that progressed in the frailty syndrome (the area under the curve value was 0.697 with 95% CI 0.566–0.827). Conclusions: Salivary IL-6 concentration can be used as potential biomarker of frailty syndrome and as a tool to monitor the effects of interventions in frail individuals.

Investigation of the relationship between periodontal and systemic inflammation in children with Sickle Cell Disease: A case- control study.

Periodontal diseases are chronic inflammatory diseases and tissue destruction increases with oxidative stress in periodontal tissues. Periodontal diseases are associated with systemic diseases such as diabetes, cardio-vascular diseases and rheumatoid arthritis by means of systemic inflammation. Sickle cell disease (SCD) is a chronic inflammatory disease in which vaso-occlusive crisis and endothelial dysfunction are present. It is not known whether the chronic systemic inflammation seen in SCD affect periodontal tissues. The aim of this study was to investigate the relationship between periodontal and systemic inflammation in children with SCD. Forty-three children with SCD and 43 healthy children were included in the study. Physical, dental and periodontal statuses were examined, blood and saliva samples were taken. Levels of pro-inflammatory and oxidative stress mediators in serum and saliva were evaluated. The periodontal findings of the groups were similar. The majority of the subjects in both groups had gingival inflammation. In SCD group, significantly higher serum high sensitive C-reactive protein (Hs-CRP), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, total oxidant status (TOS), nitric oxide (NO) and salivary IL-6 were observed (p<0.05). There were positive correlations between salivary IL-6 levels and serum Hs-CRP levels (r=0.303, p<0.05). In addition; it was determined that salivary IL-6, TNF-α and NO levels were increased 3-6 times in children with a history of painful crisis or acute chest syndrome compared to children who had never had a painful crisis or acute chest syndrome. Although, observed oral health status was similar in both groups, salivary cytokine levels were increased in children with SCD. The higher salivary cytokine levels may be associated with chronic systemic inflammation and vaso-occlusion observed in children with SCD.

Dental caries in children and COVID-19 - An interleukin association: A review of a novel concept

COVID-19 is a pandemic throughout the world, leading to the hunger of knowledge as well as evidences regarding the corona virus which causes this disease. Interleukins are the chemokines which belong to the family of cytokines which are chemotactic in nature and cause the recruitment of cells of inflammation. In the recent COVID 19 pandemic the adverse outcomes in children, though reported less, has been related to the establishment of a cytokine storm, the components of which are common with the cytokine expression profile of Dental caries and early childhood caries in children. IL-6 levels are raised in the serum of the patients infected with COVID-19. Dental caries in children has been attributed to having its pathophysiology related in a cytokine response. Salivary IL-6 levels have been found to be elevated in children with multiple carious lesions. Hypotheses The present letter aims to propose that the multiple carious lesions can be a biomarker for the patients affected with COVID 19 due to raised IL-6 levels. Evaluation of hypotheses: The authors screened the data on COVID 19 and its association with dental caries in children. This paper is an hypotheses to highlight the importance of raised levels of IL-6 as a biomarker in the saliva of children with carious lesions and those affected with COVID-19. This communication proposes the connection between COVID-19 and dental caries through their cytokine connection to form a translational basis for recommending maintenance of oral hygiene in the COVID era. Thus every dentist must suspect every patient affected with multiple carious lesions to be a carrier of COVID-19.

Changes in Th1/Th2-related cytokine expression in the saliva of patients with recurrent aphthous stomatitis before and after prednisone treatment.

To investigate the changes of T helper cell (Th)1/Th2-related cytokine expression in the saliva of minor recurrent aphthous stomatitis (RAS) patients before and after treatment with systemic prednisone. A total of 101 patients with RAS and 15 participants with normal oral mucosa as controls were enrolled in this study. The levels of cytokine expression in the whole unstimulated saliva were examined using a multiplex bead-based cytometric bead array before and after prednisone treatment at a starting dose of 15mg/day. The levels of salivary interleukin (IL)-4, IL-5, IL-6, IL-10, interferon (IFN)-γ, and tumor necrosis factor-α (TNF-α) in RAS patients were significantly higher than those of the normal controls (all P < 0.001). Importantly, the levels of salivary IL-6, IL-10, IFN-γ, and TNF-α in RAS patients were significantly decreased following prednisone treatment (all P < 0.001). Moreover, the IFN-γ to IL-4 ratio (mean: 26.9) was significantly (P < 0.001) decreased after treatment, which almost returned to normal (mean: 24.4; P > 0.05). This preliminary study demonstrates for the first time that prednisone exerts a significant therapeutic role against RAS through decreasing salivary cytokine levels and promoting a Th1/Th2 balance. Salivary cytokine profiles may provide a noninvasive, convenient, and effective approach to monitoring the course of RAS and may even be helpful to identify key pathogenic factors and potential mechanisms.

Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet's Disease.

Behçet’s disease (BD) is a chronic, multi-systemic disorder of unknown aetiology typified by recurrent oral and genital mucocutaneous lesions, uveitis and vasculitis. Innate and adaptive immune system dysregulation has been implicated in pathogenesis with alterations in serum cytokine profiles. Few studies have investigated salivary cytokines in BD, despite more than 90% of BD patients first presenting with oral ulceration. The aim of this pilot study was twofold; firstly to investigate whether cytokine levels in matched serum and saliva samples show a differential profile in BD (with and without oral ulcers), recurrent aphthous stomatitis (RAS) and healthy controls (HCs), and secondly, to explore if any differential profiles in serum and/or saliva could provide a panel of cytokines with diagnostic and therapeutic potential for BD. Concentrations of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, TNF-β) were measured using the Human Th1/Th2 11-Plex FlowCytomix™ kit with IL-17A, in BD (N=20), RAS (N=6) and HCs (N=10). A differential range of cytokines was detected in serum and saliva with the majority of cytokine levels higher in saliva. The most prevalent salivary cytokines were IL-1β, IL-2, IL-8, IL-10 and TNF-α present in all samples in contrast to serum where the most prevalent cytokine detected was IL-8 (91.9%). The least abundant cytokine was IFN-γ in both saliva (43.2%) and serum (2.7%). After normalizing saliva for protein content, BD patients with oral ulcers (BD-MA) had significantly higher levels of salivary IL-1β (p=0.01), IL-8 (p=0.02), TNF-α (p=0.004) and IL-6 (p=0.01) than HCs. Notably, BD patients without oral ulcers (BD-MQ) also had significantly higher salivary IL-1β, IL-8 and TNF-α (p ≤ 0.05) than HCs. During relapsed (BD-RE) and quiet (BD-Q) systemic episodes, salivary IL-β and TNF-α were also significantly increased with IL-8 significantly higher only in BD-Q (p=0.02). BD oral ulcers signify a potential reactivation of systemic inflammation. Identifying cytokines released during asymptomatic episodes and oral ulceration might lead to targeted drug therapy to prevent recurrent oral ulcers and possible disease relapse. This is the first study to report salivary cytokine levels in BD. The detectable levels suggests cytokine profiling of BD saliva may provide an alternative, less invasive, sensitive procedure for frequent monitoring of disease activity and progression.