Salivary Cytokines Research Articles

Salivary Th17 cytokine, human β-defensin 1–3, and salivary scavenger and agglutinin levels in Crohn’s disease

ObjectivesCrohn’s disease patients, who are prone to develop periodontal diseases, may carry genetic defects in their Th17 cytokine, human beta-defensin (hBD) 1–3, and salivary and scavenger agglutinin (SALSA) expressions. Biochemical composition of saliva reflects the oral consequences of systemic immune response modifications. Our aim was to evaluate the salivary Th17 cytokine, epithelial hBD 1–3, and SALSA levels in relation to Crohn’s disease.Materials and methodsThis cross-sectional study included 42 Crohn’s disease patients and 34 systemically healthy controls. Periodontal and dental indexes were measured, and stimulated saliva samples were collected. Salivary Th17 cytokine levels were analyzed by multiplex technique, and hBD 1–3 and SALSA levels by enzyme-linked immunosorbent assay.ResultsThere were 19 gingivitis and 11 initial periodontitis patients in the Crohn’s disease group, and 15 gingivitis and 4 initial periodontitis in the control group. In comparison to controls, higher salivary Th17 cytokine levels were observed in Crohn’s disease patients. No statistical difference was observed between Crohn’s disease and control groups in terms of their salivary hBD 1–3 and SALSA levels. Based on the regression analysis, there is no independent association between Crohn’s disease and salivary Th17 cytokine levels.ConclusionsCrohn’s disease does not relate to salivary antimicrobial hBD 1–3 or SALSA levels. While Crohn’s disease patients have higher salivary Th17 cytokine levels in comparison to systemically healthy controls, an independent association between Crohn’s disease and Th17 cytokine profile is still missing.Clinical relevanceDiminished Th17 cytokine response in Crohn’s disease, which might be related to genetic susceptibility, can be also visualized in saliva.

Associations between Social Adversity and Biomarkers of Inflammation, Stress, and Aging in Children

BackgroundPrior work has found relationships between childhood social adversity and biomarkers of stress, but knowledge gaps remain. To help address these gaps, we explored associations between social adversity and biomarkers of inflammation (interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor-alpha [TNF-α], and salivary cytokine hierarchical “clusters” based on the three interleukins), neuroendocrine function (cortisol, cortisone, dehydroepiandrosterone, testosterone, and progesterone), neuromodulation (N-arachidonoylethanolamine, stearoylethanolamine, oleoylethanolamide, and palmitoylethanolamide), and epigenetic aging (Pediatric-Buccal-Epigenetic clock).MethodsWe collected biomarker samples of children ages 0–17 recruited from an acute care pediatrics clinic and examined their associations with caregiver-endorsed education, income, social risk factors, and cumulative adversity. We calculated regression-adjusted means for each biomarker and compared associations with social factors using Wald tests. We used logistic regression to predict being in the highest cytokine cluster based on social predictors.ResultsOur final sample included 537 children but varied based on each biomarker. Cumulative social adversity was significantly associated with having higher levels of all inflammatory markers and with cortisol, displaying a U-shaped distribution. There were no significant relationships between cumulative social adversity and cortisone, neuromodulation biomarkers or epigenetic aging.ConclusionOur findings support prior work suggesting that social stress exposures contribute to increased inflammation in children.ImpactOur study is one of the largest studies examining associations between childhood social adversity and biomarkers of inflammation, neuroendocrine function, neuromodulation, and epigenetic aging. It is one of the largest studies to link childhood social adversity to biomarkers of inflammation, and the first of which we are aware to link cumulative social adversity to cytokine clusters. It is also one of the largest studies to examine associations between steroids and epigenetic aging among children, and one of the only studies of which we are aware to examine associations between social adversity and endocannabinoids among children. Clinical Trial Registration: NCT02746393

Kinetics of neutrophil extracellular traps and cytokines in oral mucositis and Candida infection.

This study investigated the concentrations of neutrophil extracellular traps (NET) and salivary cytokines (IL-1β, IL-6, IL-8/CXCL8, TNF, and TGF-β1) in patients undergoing chemotherapy and their associations with oral mucositis (OM) and Candida infection. This prospective longitudinal study performed at a Brazilian service included 60 adults diagnosed with hematolymphoid diseases. Saliva samples were collected on days D0, D3, D10, and D15. Cytokines were analyzed by ELISA and NET formation by identification of the myeloperoxidase-DNA complex. Oral Candida spp. was cultured. OM occurred in 43.3% of patients and oral candidiasis in 20%. However, 66% of individuals had positive cultures for C. albicans. Higher concentrations of IL-6, IL-8/CXCL8, and TNF and lower concentrations of TGF-β1 were observed in patients with OM. C. albicans infection contributed to the increase in IL-8/CXCL8, TGF-β1, and TNF. Individuals with OM or with oral candidiasis had significant reductions in NET formation. In contrast, individuals with C. albicans and with concomitant C. albicans and OM exhibited higher NET formation. The kinetics of cytokine levels and NET formation in chemotherapy-induced OM appears to be altered by Candida infection, even in the absence of clinical signs of oral candidiasis.

SALIVARY IL-6 AND IL-8 AS POTENTIAL BIOMARKERS FOR ORAL SQUAMOUS CELL CARCINOMA

Introduction: Early identification of oral squamous cell carcinoma (OSCC) is a crucial factor influencing the disease's prognosis. The elevated levels of IL-6 and IL-8 in saliva are a result of their overproduction in the cancer microenvironment. The production of salivary cytokines, particularly IL-6 and IL-8, has a role in cancer development. These cytokines may also be used as biomarkers. The use of saliva as a biomarker is quite interesting because it is in direct contact with cancer cells, easy to access, non-invasive, and cost-effective. Aim: The aim of this literature review was to assess the potential of salivary IL-6 and IL-8 as biomarkers for OSCC early diagnosis. Review: The initiation of carcinogenesis in the oral cavity is actively repressed by inflammation and cell-mediated immunity. IL-6 and IL-8 are two important molecules involved in stromal-to-cancer cell communication. These cytokines play a major part in the growth, progression, metastasis, and recurrence of OSCC. Several studies have found that OSCC patients have higher levels of salivary IL-6 and IL-8 than healthy people and patients with an oral potentially malignant disorder (OPMD). Conclusion: Salivary IL-6 and IL-8 are very promising potential biomarkers for the early diagnosis of OSCC. Further research is still needed to validate and use these biomarkers clinically.

Saliva-Based Protein Analysis in Pediatric Dentofacial Inflammation.

Saliva contains various proteins that are important in developing inflammatory processes and their prevention. One key aspect of saliva research is the relationship between oral infections and inflammation, and the role of some salivary proteins. To demonstrate which salivary cytokines can be biomarkers of acute odontogenic oral and facial infections in children. The study included two groups of patients: a study group of 28 children: 7 girls and 21 boys aged 3 -17 years with acute dentofacial inflammation (DI) and a control group of 52 children: 16 girls and 36 boys aged 4-17 years with uncomplicated dental caries (CE). The levels of Interleukin-5 (IL-5), Interleukin -10 (IL-10), Interleukin-17A (IL-17A), Interleukin-12p70 (IL-12p70), Eotaxin, Rantes, Vascular Endothelial Growth Factor (VEGF), and Interferon gamma-induced protein 10 (IP10) in the saliva of children in DI and CE groups were compared. Statistical analysis was performed with Statistica 13. The Student's t-test and the Wilcoxon signed-rank test were used. The results show that IL-10, IL-17A, and Eotaxin showed a statistically significant increase in the DI group compared to the CE group. The significance level for IL-10 was p=0.02, for IL-17A was equal to Eotaxin and p=0.04. The other measured parameters did not differ statistically significant between the two groups. IL-10, IL-17A, and Eotaxin can be used as potential biomarkers for tooth-related inflammatory states of the oral cavity and face in children. These biomarkers can be useful in identifying and monitoring the presence of inflammation in the oral cavity and face.

Convergence of inflammatory response: Salivary cytokine dynamics in coronavirus disease 2019 and periodontal disease.

Periodontal disease is associated with immune dysregulation, and cytokines released can add on to the coronavirus disease 2019 (COVID-19)-associated cytokine storm, further worsening the related adverse outcomes. Specific studies investigating cytokine levels in COVID-19 patients with periodontal disease are lacking. Examining the correlation between these conditions could aid in categorizing risk categories, determining referrals, and strengthening oral hygiene protocols. The current study sought to evaluate cytokine levels in the saliva of COVID-19-positive patients with and without periodontal disease. Twenty-six COVID-19-positive patients were subjected to periodontal examination, saliva collection, and assessment of cytokine levels through cytokine bead-based multiplex assay, using fluorescence-encoded beads with flow cytometry (BD FACS LSRFortessa). Eleven cytokines were assessed (interleukin [IL] 2, 4, 6, 10, 17A, and interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2/monocyte chemoattractant protein-1), C-X-C motif chemokine ligand (CXCL) 8/IL 8, CXCL 9/monokine-induced gamma interferon [MIG]), and CXCL 10 (chemokine IFN-gamma inducible protein 10 kDa). The cytokine levels of the recruited subjects were also compared graphically with the salivary cytokine levels reported in the literature for health, COVID-19, and periodontal disease alone. Out of 26 COVID-19-positive patients, 17 had periodontal disease. Levels of all cytokines were raised in patients with both diseases when compared to values reported in literature for health, periodontal disease alone, or COVID-19 alone. However, there was no statistical difference among the recruited subjects for IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-gamma, TNF-α, CCL2, CXCL 8, and CXCL 10. MIG levels were found to be higher in periodontally healthy, COVID-19-positive subjects (P = 0.01). Periodontal disease might contribute to the COVID-19-induced cytokine storm, potentially amplifying its impact.

The Effect of Saliva and Dental Caries of the Patients with Hashimoto Thyroiditis on Cytokine Levels.

This study aimed to evaluate the effect of dental caries and oral health of patients on salivary cytokine levels with Hashimoto's thyroiditis (HT). The study included 30 patients (n = 30) diagnosed with HT. The standardization of the participants was achieved with specific biochemical parameters, and the sociodemographic information of the patients was obtained through anamnesis. A pH meter was employed for salivary pH measurement. After determining the oral problems of the patients, necessary treatments were applied. Following 3 months of treatment, saliva samples were taken to evaluate cytokine levels (TNF-α, IL-6, IL-8, and CRP) and for ELISA analyses. The Wilcoxon test was used for pairwise comparison of nonparametric data, and the Chi-square test was employed to analyze categorical variables at P < 0.05. There was a significant decrease in salivary TNF-α, IL-6, IL-8, and CRP levels between the measurements before and after 3 months of treatment (P < 0.05). In addition, a significant increase was found in salivary pH (P < 0.05). The salivary cytokine levels decrease and the inflammatory response improves when the inflammation in the periodontal tissues and dental caries is treated.

Dietary inflammatory index in relation to salivary cytokine concentrations and periodontitis: A cross-sectional analysis.

To examine the associations of dietary inflammatory index (DII) with salivary cytokine concentrations and periodontitis after controlling for body mass index (BMI), socio-demographic factors and lifestyle. Subgroups from two Finnish surveys, DILGOM 2007 and Health 2000, were included (total n = 727). The DII scores were calculated based on a food frequency questionnaire. Periodontal status was assessed with a cumulative risk score in DILGOM 2007 and by pocket depth measurement in Health 2000. From saliva, interleukin (IL)-1β, IL-1 receptor antagonist, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α concentrations were measured. The DII scores did not differ between non-periodontitis and periodontitis participants in pairwise comparison. After adjusting for energy intake, periodontal status, BMI, age, education level, smoking habit and physical activity, DII was not associated with salivary cytokine concentrations. After adjusting for salivary cytokine levels and other confounding factors, DII was associated with periodontitis in the Health 2000 subgroup but not in the DILGOM 2007 subgroup. The current data support the evidence that diet is not associated with salivary cytokine levels but may be associated with periodontitis. The association observed between diet and periodontitis is related to factors other than diet-dependent inflammatory tendency in the oral cavity.

Saliva as a potential non-invasive liquid biopsy for early and easy diagnosis/prognosis of head and neck cancer

Head and neck squamous cell carcinomas (HNSCCs) are the most devastating diseases in India and southeast Asia. It is a preventable and curable disease if detected early. Tobacco and alcohol consumption are the two major risk-factors but infection of high-risk HPVs are also associated with development of predominantly oral and oropharyngeal carcinomas. Interestingly, unlike cervical cancer, HPV-induced HNSCCs show good prognosis and better survival in contrast, majority of tobacco-associated HPV−ve HNSCCs are highly aggressive with poor clinical outcome. Biomarker analysis in circulatory body-fluids for early cancer diagnosis, prognosis and treatment monitoring are becoming important in clinical practice. Early diagnosis using non-invasive saliva for oral or other diseases plays an important role in successful treatment and better prognosis. Saliva mirrors the body's state of health as it comes into direct contact with oral lesions and needs no trained manpower to collect, making it a suitable bio-fluid of choice for screening. Saliva can be used to detect not only virus, bacteria and other biomarkers but variety of molecular and genetic markers for an early detection, treatment and monitoring cancer and other diseases. The performance of saliva-based diagnostics are reported to be highly (≥95 %) sensitive and specific indicating the test's ability to correctly identify true positive or negative cases. This review focuses on the potentials of saliva in the early detection of not only HPV or other pathogens but also identification of highly reliable gene mutations, oral-microbiomes, metabolites, salivary cytokines, non-coding RNAs and exosomal miRNAs. It also discusses the importance of saliva as a reliable, cost-effective and an easy alternative to invasive procedures.

Lung function is related to salivary cytokines and hormones in healthy children. An exploratory cross‐sectional study

AbstractPulmonary mechanics has been traditionally viewed as determined by lung size and physical factors such as frictional forces and tissue viscoelastic properties, but few information exists regarding potential influences of cytokines and hormones on lung function. Concentrations of 28 cytokines and hormones were measured in saliva from clinically healthy scholar children, purposely selected to include a wide range of body mass index (BMI). Lung function was assessed by impulse oscillometry, spirometry, and diffusing capacity for carbon monoxide, and expressed as z‐score or percent predicted. Ninety‐six scholar children (55.2% female) were enrolled. Bivariate analysis showed that almost all lung function variables correlated with one or more cytokine or hormone, mainly in boys, but only some of them remained statistically significant in the multiple regression analyses. Thus, after adjusting by height, age, and BMI, salivary concentrations of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in boys were associated with zR5‐R20 and reactance parameters (zX20, zFres, and zAX), while glucagon inversely correlated with resistances (zR5 and zR20). Thus, in physiological conditions, part of the mechanics of breathing might be influenced by some cytokines and hormones, including glucagon and GM‐CSF. This endogenous influence is a novel concept that warrants in‐depth characterization.

Elevated pro-inflammatory cytokines and chemokines in saliva of cats with feline odontoclastic resorptive lesion

Feline odontoclastic resorptive lesion (FORL) is an inflammatory oral disease of unknown aetiopathogenesis that affects between 20% to 75% of cats. Twenty immune-associated molecules were measured in saliva of 25 healthy and 40 cats with FORL using a multiplex assay. No statistically significant differences were observed in the levels of these proteins between the healthy group and the diseased group of cats. A two-step cluster analysis of the oral microbiome and salivary cytokine data identified two subgroups of cats with FORL: FORL-1 (subset of cats with a less diverse oral microbiome) and FORL-2 (diseased cats with a microbiome similar to that of healthy animals). The level of some key proinflammatory cytokines (IL-1β, IL-12p40) and chemokines (IL-8, RANTES, KC) were significantly higher in the FORL-1 subgroup than in the FORL-2 subgroup and the healthy group. In addition, TNF-α levels were greater in the FORL-1 subgroup than in the FORL-2 subgroup. These increases in pro-inflammatory cytokines and chemokines indicate active ongoing inflammation that may promote the osteoclastic/odontoclastic activity associated with FORL.

Correlation between salivary cytokine profiles and white spot lesions in adolescent patients receiving clear aligner orthodontic treatment

BackgroundTo explore the relationship between changes in salivary cytokine levels and the occurrence of white spot lesions in adolescents receiving clear aligner orthodontic treatment and investigate the predictive value of various factors for lesion occurrence.MethodsWe retrospectively analyzed sixthy eight adolescent in the permanent dentition period, who received clear aligner orthodontics in our hospital were randomly divided into two groups according to the occurrence or aggravation of white spot lesions after treatment. The general condition of the oral cavity was analyzed, saliva was collected, and inflammation-related cytokines with varying transcription levels between groups were screened by transcriptome analysis. The expression levels of inflammatory cytokines in the saliva of the patients in the two groups were measured, and the risk factors for white spot lesions were screened by correlation analysis and binary logistic regression analysis. The value of the independent and combined application of risk factors for predicting the occurrence of white spot lesions in adolescent patients after invisible orthodontic treatment was analyzed by receiver operating characteristic (ROC) curve analysis.ResultsTranscriptome and GO and KEGG pathway analyses showed that there were differences in the transcription levels of inflammatory cytokines such as CXCL1, CXCL2, CXCL8, CCL3, CCL4, IL-1β and IL-2 between groups. The levels of CXCL8, CCL3, CCL4, IL-1β and IL-2 in the saliva of patients with white spot lesions were significantly higher in patients after invisible orthodontic treatment (P < 0.05). Correlation analysis and binary logistic regression analysis showed that elevated levels of CXCL8, IL-1β and IL-2 were independent risk factors for the occurrence of white spot lesions (P < 0.05). CXCL8 had the highest independent predictive value for the occurrence of white spot lesions (AUC = 0.773, P < 0.05), and the combination of IL-1β and IL-2 was also of high value in predicting the occurrence of white spot lesions.ConclusionAfter invisible orthodontic treatment, the oral microenvironment, including inflammatory cytokine levels, in adolescent patients changes; in particular, the levels of inflammatory cytokines such as CXCLs and ILs change. CXCL8 expression is significantly associated with the occurrence of white spot lesions and is an important potential target for the prevention and treatment of white spot lesions in the future.

Salivary and crevicular fluid proinflammatory cytokines and advanced glycation end products in patients with different glycemic levels undergoing fixed orthodontic treatment.

To examine whether patients with different blood glycemic levels undergoing fixed orthodontic therapy demonstrate changes in the biochemical profiles of crevicular fluid and salivary advanced glycation end products (AGEs) and proinflammatory cytokine levels in comparison with nondiabetic healthy subjects. Prediabetic subjects, subjects with type 2 diabetes mellitus (T2DM), and subjects without a diabetes mellitus diagnosis undergoing fixed orthodontic therapy with MBT prescription brackets (0.022-inch brackets and 0.019 × 0.025-inch stainless steel archwires) were included in the study. The following clinical periodontal parameters were evaluated: (1) plaque score (PS), (2) probing depth (PD), (3) bleeding on probing (BOP), and (4) clinical attachment loss. Crevicular fluid and saliva specimens were collected during regular orthodontic visits. Salivary and crevicular fluid tumor necrosis factor alpha, interleukin-6, ghrelin, resistin, AGEs, and receptor activator of nuclear factor κΒ ligand were evaluated using a human magnetic Luminex multiplex assay. BOP scores were significantly higher among T2DM subjects (19.2%) than among nondiabetic subjects (11.2%) and prediabetic subjects (15.9%). Comparable values were demonstrated by all three study groups regarding PD scores and PSs. T2DM subjects demonstrated higher scores for gingival crevicular fluid (GCF) chemokines than nondiabetic and prediabetic subjects. A statistically significant difference was found in the levels of AGEs and resistin among the three study groups. The scores revealed for the levels of GCF resistin and AGEs versus periodontal BOP demonstrated a significant positive association by the Pearson correlation test. T2DM patients demonstrated significantly higher levels of GCF resistin and AGEs during fixed orthodontic therapy. Chronic hyperglycemic patients undergoing orthodontic therapy demonstrated a proinflammatory response.

Relationship between Salivary Cytokines and HIV-Oral Lesions among Newly Diagnosed Adults with HIV in Southwest Nigeria

Relationship between Salivary Cytokines and HIV-Oral Lesions among Newly Diagnosed Adults with HIV in Southwest Nigeria

Saliva and GCF cytokine levels in insulin-dependent diabetic teens and their relationship with metabolic status and disease duration

ObjectiveHyperglycemia damages periodontal tissues by several mechanisms, primarily via dysregulated cytokine production. However, studies examining the relationship between cytokine levels, periodontal status, and diabetes-related parameters in teenage Type 1 Diabetes Mellitus (T1DM) patients are scarce. This investigation aimed to determine the levels of cytokines such as IL-33, IL-22, IL-17, IL-6, TNF-α and interferon (IFN)-γ in the saliva and gingival crevicular fluid (GCF) of T1DM teens and correlate these values with the patients’ periodontal health and DM-related parameters such as FBG, HbA1c, and diabetes duration. Material and methodsSaliva, GCF samples and full-mouth clinical periodontal recordings were obtained from 40 T1DM and 40 non-diabetic teenagers. IFN-γ, TNF-α, IL-6, IL-17, IL-22, and IL-33 levels were analyzed by ELISA. ResultsClinical bleeding on probing (BOP) and periodontal probing depth measures did not differ between the groups. The plaque and gingival index, as well as saliva and GCF levels of all cytokines tested were found to be comparatively higher in the cases. Correlations were detected between the duration of DM and salivary IL-17 and IL-33 levels, between FBG and GCF IL-17 levels, and between BOP and salivary IL-33 levels. Salivary IL-17 and IL-33 levels showed significant correlation solely with the duration of DM. ConclusionsIL-33 and IL-17 appear to be a potent combination of cytokines in regulating salivary composition over time in Type I diabetic teens. A better understanding of the time-dependent release of salivary cytokines in Type I diabetic teens may help develop treatment strategies and improve oral health.

Salivary inflammatory burden in pre- and postmenopausal women: Associations with body mass index, patient-reported health, serum cytokines, and periodontal parameters.

The decline of estrogen levels during menopause impacts weight, mood, and overall health, both orally and systemically. This study assessed salivary levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-10, and IL-7 in postmenopausal (PMW) and regularly menstruating premenopausal (RMPW) women, while considering serum cytokine levels, body mass index (BMI), periodontal health, and self-reported physical and emotional well-being. In this study, 75 PMW and 71 RMPW were included. Clinical and periodontal parameters were evaluated, and perceived health was assessed with the Women's Health Questionnaire (WHQ). Cytokine levels in both saliva and serum were quantified by enzyme-linked immunosorbent assay (ELISA). Covariate evaluations of salivary cytokines were conducted using hierarchical linear regression modeling. Cytokines weredetectablein saliva from 71 PMW and 67 RMPW. In the initial unadjusted model, IL-7, IL-10, and TNF-α exibited significant differences between RMPW and PMW. However, these differences became non-significant (p>0.05) in the final model after adjusting for age, which implies a negligible effect of the investigated covariates on salivary cytokine levels when age was considered. Lower levels of IL-6 in PMW, which initially showed no significant difference, became borderline (p=0.054) in the final model after adjusting for age. After adjusting for multiple factors, no significant difference was found in the salivary levels of the investigated cytokines between RMPW and PMW. Factors such as BMI, perceived health, serum cytokine levels, and periodontal parameters seem to minimally influence these levels in PMW. However, age may be a stronger confounding factor.

Salivary Cytokine Profile in Patients with Oral Lichen Planus

This study aimed to determine salivary concentrations of interleukin (IL)-1β, IL-2, IL-10, IL-23, transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, nitrate (a by-product of nitric oxide oxidation), and cortisol in patients with oral lichen planus (OLP). Twenty patients diagnosed with OLP and 20 sex-matched healthy volunteers (HV) were included in this cross-sectional study. Unstimulated whole saliva was collected in the morning. Salivary cytokine and cortisol concentrations were determined by enzyme-linked immunosorbent assays (ELISA). Nitrate was measured in a nitric oxide analyzer. We found higher salivary concentrations of IL-2 (p&lt;0.003), IL-23 ( p&lt;0.04), and TGF-β (p=0.05) in patients with OLP compared to HV. No significant differences were found in salivary levels of TNF-α, IL-1β, or IL-10. Nitrate concentrations were markedly increased in OLP patients (1,227.0 ± 738.8 µM/mg total protein) when compared to HV (261.6 ± 166.8 µM/mg; p&lt;0.0001). Salivary cortisol levels were also higher in OLP patients (2.79 ± 1.39 vs. 1.94 ±1.21 ng/mg; p&lt;0.048). The markedly increased salivary levels of nitric oxide in patients with OLP suggest a relationship of this molecule with the cell death and tissue damage observed in these lesions.

Increased Salivary IL-1 Beta Level Is Associated with Poor Sleep Quality in University Students.

Poor sleep quality is a major public health concern for all ages. In particular, university students often face stress levels and changes in social life habits that negatively influence their quality of sleep. This could be associated with psychological well-being in terms of anxiety and depressive symptoms, stress levels, and a poor self-perceived health status. The increases in the pro-inflammatory cytokine interleukin 6 (IL-6), IL-1 beta (IL-1β), and tumor necrosis factor alpha (TNFα), in blood have been linked to poor sleep quality in many diseases, but data on salivary cytokine levels in students are missing or are seldom analyzed. In this study we determined the quality of sleep in a sample of university students and the role of psychological assessment and factors affecting sleep (alcohol intake, tobacco, consumption of stimulant drinks, exercise, and body mass index). We also aimed to shed new light on the associations between sleep quality and salivary inflammatory cytokines (IL-1β, IL-6, and TNFα). Sleep quality was measured with the Athens Insomnia Scale (AIS) and Pittsburgh Sleep Quality Index (PSQI). Perceived stress was assessed using Cohen's Perceived Stress Scale (PSS), and the Goldberg Anxiety and Depression Scale (GADS) was used to assess the level of anxiety or depression. Perceived health status was measured with a visual analogue. Saliva samples was taken in the morning and the inflammatory cytokines was measured via enzyme-linked immunoassay. There was a direct and significant association between the salivary IL-1β concentration and AIS score (r = 0.248; p = 0.038, Pearson correlation) and Pittsburgh scale score (r = 0.274; p = 0.022, Pearson correlation). The relationship between IL-1β and AIS controlling for sex, age, and chronic disease, is still significant (r = 0.260; p = 0.033). The relationship between IL-1β and PSQI controlling for the influence of these variables is also significant (r = 0.279; p = 0.022). Salivary IL-1β concentrations were not significantly associated with any of the scores of the other psychological assessments (PSS, anxiety, depression symptoms, or self-perceived health). Salivary TNFα was significantly and inversely associated with self-perceived health (r = -0.259; p = 0.033, Pearson correlation), but the salivary IL-6 concentration was not associated with any of the sleep quality scale or psychological assessment scores. Our results provide a novel relationship between pro-inflammatory cytokine IL-1β in saliva and poor sleep quality. However, the role of inflammation in poor sleep quality requires further study to identify strategies that could lower inflammation and thus, likely improve sleep quality.

A population-based study of children suggests blunted morning cortisol rhythms are associated with alterations of the systemic inflammatory state

BackgroundIn children, digital media, lifestyle, and the COVID pandemic have impacted sunlight exposure, exercise, and diet patterns - cues that entrain the circadian clock. We hypothesized that low morning cortisol reflects a weak circadian clock, impacting the pro-inflammatory state. The primary objective was to test relationships between diurnal cortisol fluctuations and the inflammatory state in children as a means of providing indirect support for this hypothesis. MethodsThe Cardiovascular Health Intervention Program (CHIP) was a population-based cross-sectional and longitudinal study of circadian health in public elementary school children in Southern Maine, USA (recruitment period 2012–2017). Participants were 689 students in 4th grade (baseline; age=9.2 ± 0.4 years), and 647 students in 5th grade (age=10.5 ± 0.5 years). Nine salivary cortisol measures per child (2 awakening and 1 prior to bed for 3 sequential days) (n = 1336 child phenotype days; n = 7987 cortisol assays), 10 cytokines measured in morning and evening saliva samples (n = 202 child phenotype days), and lipids were measured. Clinical outcomes were blood pressure, weight and height (body mass index [BMI]; BMI = kg/m2), among others. FindingsUpon-waking cortisol levels were 0.28 ± 0.13 µg/dL, 30-minute post-waking 0.33 ± 0.15 µg/dL, and evening 0.08 ± 0.10 µg/dL. Salivary cytokine levels (n = 202) showed interleukins (IL) IL-1β and IL-8 were highest in early morning (upon awakening; AM), and IL-6 and tumor necrosis factor (TNF) TNF-α highest before bed (PM) (IL-1β AM > PM [−4.02 fold; p < 0.001]; IL-8 AM > PM [−1.36 fold; p < 0.001]; IL-6 AM < PM [+1.49 fold; p < 0.001]; TNF-α AM < PM [+1.73 fold; p = 0.03]. Regression modeling showed high morning cortisol was associated with high morning IL-1β (p = 3.82 ×10−6), but low evening IL-1β (p = 6.27 ×10−4). Regression modeling of BMI z-score as the response variable showed the expected significant relationships to high density lipoprotein (HDL) (negative; p < 0.001), mean arterial pressure (positive; p < 0.001), and morning cortisol (negative; p = 0.01) but only weak relationships to either evening cortisol (p = 0.1) or cytokine (positive; p = 0.02; from the model with smallest Rsquared) levels. InterpretationWe provide preliminary data on diurnal fluctuations of inflammatory cytokines in saliva in a population-based cohort of children. Correlation of morning and evening cortisol levels with inflammatory cytokines in the same saliva samples showed that high morning cortisol was associated with high morning IL-1β and low evening IL-1β. Future studies may test the hypothesis that strong diurnal cycling of IL-1β may serve as a homeostatic mechanism keeping the immune system in check, and that low morning cortisol (possible circadian misalignment) may lead to less stringent control of inflammatory networks.

Deregulation of cytokine affecting oral neutrophil subsets in oral cancer.

The most prevalent form of leukocytes in human blood, neutrophils, is regarded as an essential part of the innate immune system and the body's 1st line of defense against foreign invaders. However, divergent opinions arise on the role of neutrophils in cancer, likely due to the occurrence of many neutrophil subsets. Several factors in the tumor microenvironment were found to modify the phenotype and function of neutrophils. Inhibitory cytokine production and recruitment of protumor immune cells to the tumor microenvironment are the reasons for immune suppression. Although some salivary cytokines were found to be increased in cancer patient's saliva, simultaneously, it was observed that those cytokines are high in other oral inflammatory conditions. So, it is challenging to distinguish at what level of expression those cytokines are involved in the neoplastic process. Therefore, the goal of this study is to provide a summary of the current information about the existence and presence of specific cytokines that impact cPMN and TAN and their potential activities in the context of healthy and cancer states so that we can relate to oPMN.