Salivary Inflammatory Cytokines Research Articles

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.

Changes in the level of cytokines in the saliva of hypertensive patients with chronic periodontitis after scaling and root planning

IntroductionCytokines have a key role in the pathogenesis of both hypertension and periodontitis. Salivary diagnosis is a promising field with numerous clinical applications. Since limited studies have been carried out on how salivary inflammatory cytokines can be determined and how well periodontal disease and hypertension might react to scaling and root planning (SRP). The goal of this study was to identify the pattern of changes in salivary inflammatory cytokines in chronic periodontitis subjects with hypertension after nonsurgical periodontal therapy. MethodsIt included observational trial recruited 94 chronic periodontitis patients, 44 of whom had hypertension. All subjects have undergone non- surgical periodontal treatment. The clinical periodontal parameters included gingival index (GI), plaque index (PI), and probing of pocket depth (PPD). Unstimulated saliva was collected to determine the inflammatory biomarkers (using a commercial Elisa kit) both before and after SRP ResultsIn comparison to non-hypertensive participants, the periodontal PPD was significantly higher in hypertensive subjects. All clinical parameters in the first examination, except for PI, were significantly higher in hypertensive than in non-hypertensive subjects. Plaque Index, GI, and PPD parameters at first visit and after finishing treatment positively correlated with salivary IL-1β, excluding pretreatment GI. The current results demonstrate the presence of a positive correlation between diastolic blood pressure and TNF (r = 0.330 and P = 0.029). All patients enrolled in this study showed a significant increase in the salivary levels of IL-4 after SRP. ConclusionsThe current study offer important and valuable information concerning the practical application of pro-inflammatory and anti-inflammatory cytokines as useful biomarkers and indicators for determining the outcome of SRP and progression of chronic periodontitis in patients with hypertension.

Role of selected salivary inflammatory cytokines in the diagnosis and prognosis of oral squamous cell carcinoma. A Systematic Review and Meta-analysis.

Oral squamous cell carcinoma (OSCC) is gradually increasing its incidence in our society. Unfortunately, this entity is diagnosed at an advanced stage in most patients, a fact that implies greater difficulty in its treatment and a worse prognosis. This systematic review aims to assess whether the cytokines IL-6, IL-8 and TNF-α are potential salivary biomarkers that allow early diagnosis of cancer. An electronic search was performed in three databases (Pubmed, Scopus and Web of Science). We used the following keywords: "salivary cytokines", "saliva cytokines", "salivary interleukins", "biomarkers", "oral squamous cell carcinoma" and "diagnosis", combined with the Boolean operators "AND" and "OR". 128 publications were found and finally 23 articles were included in the review and 15 in the meta-analysis. It has been observed that the majority of OSCC patients express higher salivary concentrations of IL-6, IL-8 and TNF-α compared to the control (CL) and premalignant lesion (OPML) groups. It has also been observed that the different premalignant lesions do not have statistically significant differences in the salivary concentration of the cytokines, and on the other hand, differences have been observed between the different TNM stages. The meta-analysis has shown that the difference in concentration of IL-6, IL-8 and TNF-α is statistically significant between the CL group and the OSCC, and also between the CL group and OPML. There is sufficient evidence to affirm that IL-6, IL-8 and TNF-α are useful salivary cytokines in the early diagnosis and prognosis of OSCC. Although future studies are necessary to establish greater reliability of these biomarkers and thus be able to develop a valid diagnostic test.

Salivary inflammatory cytokines echo the low inflammatory burden in liver-transplanted children

The aims of this study were to compare the salivary cytokine profile, as a potential replacement for blood tests, in liver-transplanted children to that of a control group of healthy children, and to correlate the values of commonly tested laboratory blood tests to those of published blood values. Liver-transplanted children, and a control group of healthy children of the same sex and age distribution, were recruited for the study. Saliva was collected at the same appointment for routine blood tests for the liver-transplanted children. Saliva was also collected from a control group of healthy children with similar age and sex distributions. Normal healthy blood values were extracted from the literature, for comparison. Cytokine levels in the saliva were quantified with ELISA. The analysis compared serum and saliva values between liver-transplanted and healthy children. In the serum, the values of albumin, GIT, GPT, GGT, CRP, WBC, neutrophils, and lymphocytes were examined, while the levels of IL-6, CXCL1, IL-1b, and IL-10 were measured in the saliva. Thirty liver-transplanted children and 30 healthy children were included in the study. Compared with published data for healthy children, the liver-transplanted group showed similar hepatic serum levels, yet reduced levels of serum inflammatory markers. Compared with the control group, in the transplanted group, the mean value of IL-6 was lower and the mean value of CXCL1 was similar. Interestingly, the anti-inflammatory IL-10 cytokine was lower in the transplanted group, while the pro-inflammatory IL-1β cytokine was higher. The salivary inflammatory markers examined showed a similar pattern to the serum inflammatory values, though different markers were examined in the serum and saliva. The current study stresses the potential of oral fluids as an accessible biofluid, for use as a diagnostic substrate for systemic and oral diseases. 0136-16-RMC, Registered on 01 March 2018.

Best practice recommendations for the measurement and interpretation of salivary proinflammatory cytokines in biobehavioral research

Despite the integration of salivary inflammatory cytokines into research across the biobehavioral, psychological, clinical, and health-related disciplines, there is little guidance regarding the biospecimen collection, handling, and storage practices that maximize the quality and validity of salivary cytokine data. Furthermore, associations between salivary cytokines and measures related to oral health are rarely assessed and accounted for in studies outside the oral health fields. To address these gaps, we examine the sensitivity of salivary interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) to changes in saliva sample collection technique and cold chain management procedures. Using subsets of saliva samples collected from 150 healthy adults, we measure salivary IL-1β, IL-6, IL-8, TNF-α, and other oral health-related indices (i.e., blood contamination [transferrin], and salivary matrixmallotprotienase-8). In addition to examining changes in cytokine levels associated with sample collection technique and cold chain management procedures, we assess relations between cytokine concentrations and levels of other oral health-related measures. We found that IL-1β, IL-6, and IL-8 were more robust to changes in sample collection and cold chain management procedures than TNF-α, and all cytokines were positively associated with other oral health-related measures. Based on our findings, we recommend analyte-specific guidance for measuring and interpreting salivary cytokine concentrations.

Remitted depression and cognition in HIV: The role of cortisol and inflammation

In major depressive disorder (MDD) and remitted MDD (rMDD) alterations in cortisol and inflammation are associated with cognitive difficulties, but these relationships have not been investigated in HIV. We used secondary data from a placebo-controlled, cross-over study of cognitive performance following a probe of the hypothalamic-pituitary-adrenal (HPA) axis (low dose hydrocortisone; LDH 10 mg) in 65 people with HIV (PWH; 36 women). Using placebo data, we examined sex-specific associations between two biomarkers – basal afternoon salivary cortisol and salivary inflammatory cytokines - cognition, and rMDD. Salivary cortisol and inflammatory biomarkers were sampled across the 5 -h study. The panel of inflammatory markers included interleukin (IL)-6, IL-8, IL-1β, tumor necrosis factor-(TNF)-α, CRP, interferon gamma-induced protein (IP-10), monocyte chemotactic protein (MCP)-1, monokine induced by interferon (MIG), matrix metalloproteinase MMP-9, and MMP-1. Learning, memory, attention/concentration, and executive function were assessed 30 min and 4 h after the placebo intervention; visuospatial ability was also assessed 30 min after the placebo intervention. For women but not men with HIV, basal cortisol concentrations were higher in rMDD versus noMDD groups, and related to poorer learning and memory. For men and women with HIV, basal inflammatory cytokines were higher in rMDD versus noMDD groups, but were negatively related to cognition independent of rMDD status. Cortisol and cytokines relate to cognition in PWH, but the associations depended on sex, rMDD status, and their interaction.

Mediators of Inflammation as a Link Between Diabetes Mellitus and Periodontal Breakdown

Abstract Our objective was to investigate immunological changes that occur in saliva of subjects with type 2 diabetes mellitus (T2DM) without signs of periodontal disease and to establish if salivary inflammatory cytokines are a possible link between diabetes mellitus and periodontal breakdown. Material and methods. Twenty T2DM subjects with no periodontal disease and twenty healthy controls were registered for the present study. TNF-α and IL-6 level from saliva and serum were measured. Periodontal tissue samples were histologically examined. Results: TNF-α and IL-6 levels were higher in T2DM subjects compared to controls, with an extremely significant difference in saliva (p<0.001). Significant inflammation, affecting both epithelial and connective tissues was present in periodontal biopsies. Conclusions: The subjects showed an increased TNF-α and IL-6 levels, both in serum and -mostly in -saliva of diabetics without signs of periodontal disease, confirming the hypothesis of immunological implication, as a correlation between periodontal disease incidence and diabetes mellitus. Histologic alterations, suggesting a local inflammatory state, were present in periodontal tissue of diabetics, confirming the above hypothesis. The study reveals that saliva analysis is a quite efficient method in testing the periodontal breakdown progression in the subjects with T2DM.

Detection of AMA-M2 in human saliva: Potentials in diagnosis and monitoring of primary biliary cholangitis

Serum anti-mitochondrial antibody type 2 (AMA-M2) is considered as a pivotal biomarker for the diagnosis of primary biliary cholangitis (PBC). However, serological tests have many limitations, including inconvenience, invasiveness, and infection risks. Thus, a less invasive approach to detect AMA-M2 titer is desirable. We examined salivary AMA-M2 of potential PBC patients and found that AMA-M2 could be detected only in saliva of serum AMA-M2-positive PBC patients, but not in saliva of serum AMA-M2-negative PBC patients, oral lichen planus patients (OLP) patients, or healthy controls. Furthermore, the concentration of salivary AMA-M2 was positively correlated with the amount of serum AMA-M2 in patients. The salivary inflammatory cytokines were increased in the PBC, consistent with the results of serum test. These findings indicated that saliva might be a less invasive and cost-effective medium to accurately test for AMA-M2 levels and this is a promising development for the diagnosis and monitoring of PBC.

Adiponectin: Serum-saliva associations and relations with oral and systemic markers of inflammation

This study addresses gaps in our understanding about the validity and utility of using salivary adiponectin to index serum adiponectin levels. Matched blood and saliva samples were collected on a single occasion from healthy adults (n=99; age 18–36 years, 53% male). Serum and saliva was assayed for adiponectin and inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα), and saliva was also assayed for markers of blood contamination (transferrin), total protein (salivary flow rate) and matrix metalloproteinase-8 (MMP-8). We examined the extent to which salivary adiponectin was associated with serum adiponectin, and the influence of potential confounders on the serum-saliva correlation, including age, sex, body mass index, and markers of inflammation, oral health, salivary blood contamination, and flow rate. Findings revealed a modest serum-saliva association for adiponectin, and strong positive associations between salivary adiponectin and salivary levels of inflammatory cytokines, MMP-8, transferrin, and total protein. By contrast, salivary adiponectin was not related to serum levels of inflammatory activity. The magnitude of the serum-saliva association was strengthened when controlling for total protein in saliva, blood leakage into oral fluid, salivary inflammatory cytokines, and MMP-8. The pattern of findings extends our understanding of salivary adiponectin and its potential use as an index of circulating adiponectin levels.

Salivary inflammatory cytokines may be novel markers of carotid atherosclerosis in a Japanese general population: The Suita study

ObjectiveSalivary biomarkers have been recently useful of periodontal disease, which is also risk factor of atherosclerosis. However, there are few studies of the association between salivary inflammatory cytokines and carotid atherosclerosis. We aimed to clarify the association between salivary inflammatory cytokines and periodontal disease and carotid atherosclerosis in a general urban population. MethodsWe studied 608 Japanese men and women (mean age: 65.4 years) in the Suita study. Carotid atherosclerosis was evaluated by high-resolution ultrasonography with atherosclerotic indexes of intima-media thickness (IMT). Periodontal status was evaluated by the Community Periodontal Index (CPI). Salivary levels of interleukin-1β, interleukin-6, tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured by enzyme linked immunosorbent assay. The risks of carotid atherosclerosis (≥75th percentiles of mean- [0.88 mm] and Max-IMT [1.50 mm]) according to the quartiles of salivary inflammatory cytokines were compared using of adjusted-logistic regression models. Results and conclusionAll salivary inflammatory cytokines were positively associated with CPI. The adjusted odds ratios for carotid atherosclerosis of mean-IMT in the highest quartile of interleukin-6 and TNF-α were higher than those in the lowest quartiles (OR = 2.32 and 2.88; 95% confidence intervals = 1.19–4.51 and 1.51–5.49, respectively). The adjusted odds ratio for carotid atherosclerosis of mean-IMT in the highest quartile of PGE2 was greater than those in the lowest quartile in women (OR = 2.78; 95% confidence intervals = 1.11–6.95). In conclusion, higher levels of salivary inflammatory cytokines were associated with both periodontal disease and carotid atherosclerosis. Selected salivary inflammatory cytokines may be useful screening markers for periodontal disease and carotid atherosclerosis.