interleukin-8 and Sleep-Apnea--Obstructive

Adipocytokines play an important role in obstructive sleep apnea (OSA) by mediating inflammatory responses. Previous studies have reported that OSA is related to a change in the serum levels of adipocytokines; however, the results are still controversial. This meta-analysis aimed to assess the relationship between OSA and circulating level of adipocytokines in adults and children.. A comprehensive search was conducted in databases of Medline/PubMed and Scopus for pertinent articles published since their inception to July 2022. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to assess the strength of the relationship between the concentrations of adipocytokines with OSA.. In the overall analysis, contrary to IL-10, which showed a significant reduction, IL-1β, IL-4, IL-8, IL-17, and IFN- gamma showed higher levels in OSA patients in comparison with control groups (p <0.05). For adults, IL-1β, IL-8, IL-17, IL-18, vaspin, visfatin, and chemerin were linked to a greater serum levels in patients with OSA, while, IL-5 and IL-10 were detected significantly lower in adults with OSA in comparison with healthy adults (p <0.05). In children with OSA, the serum levels of IL-4, IL-8, IL-12, IL-17, IL-23, and IFN-gamma were significantly higher than healthy children (p <0.05).. The levels of inflammatory markers were found to be higher in OSA patients compared with control individuals, suggesting that adipocytokines may contribute to the pathology of OSA.

Topics: Adipokines; Adult; Child; Humans; Interleukin-10; Interleukin-17; Interleukin-4; Interleukin-8; Sleep Apnea, Obstructive

Inflammation proteins including interleukins (ILs) have been reported to be related to obstructive sleep apnea (OSA). The aims of this study were to estimate the levels for several key interleukins in OSA and the causal effects between them.. Weighted mean difference (WMD) was used to compare the expression differences of interleukins between OSA and control, and the changed levels during OSA treatments in the meta-analysis section. A two-sample Mendelian randomization (MR) was used to estimate the causal directions and effect sizes between OSA risks and interleukins. The inverse-variance weighting (IVW) was used as the primary method followed by several other MR methods including MR Egger, Weighted median, and MR-Robust Adjusted Profile Score as sensitivity analysis.. Nine different interleukins-IL-1β, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17, IL-18, and IL-23-were elevated in OSA compared with control to varying degrees, ranging from 0.82 to 100.14 pg/ml, and one interleukin, IL-10, was decreased by 0.77 pg/ml. Increased IL-1β, IL-6, and IL-8 rather than IL-10 can be reduced in OSA by effective treatments. Further, the MR analysis of the IVW method showed that there was no significant evidence to support the causal relationships between OSA and the nine interleukins-IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, and IL-18. Among them, the causal effect of OSA on IL-5 was almost significant [estimate: 0.267 (-0.030, 0.564),. Although IL-1β, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17, IL-18, and IL-23 were increasing and IL-10 was reducing in OSA, no significant causal relationships were observed between them by MR analysis. Further research is needed to test the causality of OSA risk on elevated IL-5 level.

Topics: Humans; Interleukin-10; Interleukin-12; Interleukin-17; Interleukin-18; Interleukin-2; Interleukin-23; Interleukin-4; Interleukin-5; Interleukin-6; Interleukin-8; Sleep Apnea, Obstructive

Interleukin (IL)-8 has been shown to play an important role in obstructive sleep apnea syndrome (OSAS). However, its role in OSAS development is still controversial. This meta-analysis was to explore the correlation between interleukin (IL)-8 concentration and OSAS. Database (from the inception to July 2021) searches on PubMed, Web of Science, Medline, EMBASE, and Cochrane Library were conducted for studies analyzing the correlation between IL-8 concentration and OSAS, regardless of the language of publication. Standardized mean difference (SMD) and 95% confidence intervals (CI) were used to analyze any prospective association between IL-8 concentration and OSAS. A total of 25 eligible studies, including 2301 participants and 1123 controls, were included in this meta-analysis. The included studies evaluating the association between serum IL-8 concentration and OSAS indicated that adults and children with OSAS had elevated serum concentrations of IL-8 compared with controls (SMD = 0.997, 95% CI = 0.437-1.517, P < 0.001; SMD = 0.431, 95% CI = 0.104-0.759, P = 0.01). Categorization of the study population into subgroups according to body mass index, apnea-hypopnea index (AHI), ethnicity, and sample size also showed that individuals with OSAS had elevated serum concentrations of IL-8 compared with controls. Additionally, the results demonstrated that the higher the AHI, higher was the IL-8 concentration. Similar results were observed in the literature on the association between plasma IL-8 concentration and OSAS. This meta-analysis verified that compared with controls, children and adults with OSAS have significantly elevated IL-8 concentrations.

Topics: Adult; Aged; Body Mass Index; Bronchoalveolar Lavage Fluid; Child; Ethnicity; Humans; Interleukin-8; Middle Aged; Nasal Lavage; Palatine Tonsil; Publication Bias; Regression Analysis; Sleep Apnea, Obstructive; Sputum

Our meta-analysis was performed to estimate the effect of continuous positive airway pressure (CPAP) therapy on systemic inflammation in patients with obstructive sleep apnea (OSA).. A comprehensive literature search of PubMed and EMBASE was performed for literature published up to January 2013. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy.. A total of 35 studies involving 1985 OSA patients were included in the meta-analysis. Each study investigated one or more inflammatory markers: 24 studies on C-reactive protein (CRP), 16 studies on IL-6, 3 studies on IL-8, and 12 studies on tumor necrosis factor α (TNF-α). The results showed that the SMD (95% confidence interval [CI]) for CRP, IL-6, IL-8, and TNF-α were 0.452 (95% CI, 0.252-0.651), 0.299 (95% CI, 0.001-0.596), 0.645 (95% CI, 0.362-0.929), and 0.478 (95% CI, 0.219-0.736) in pre- and post-CPAP therapy, respectively. The subgroup analyses seemed to support better benefits with therapy duration of ≥3 months and more adequate compliance (≥4 h/night).. CPAP therapy could partially suppress systemic inflammation in OSA patients, and substantial differences were present among the various inflammatory markers.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Continuous Positive Airway Pressure; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Sleep Apnea, Obstructive; Treatment Outcome; Tumor Necrosis Factor-alpha

Obstructive sleep apnea (OSA) has been linked to and is associated with increased cardiovascular and cerebrovascular morbidity. Ongoing inflammatory responses play an important role in this association. Multiple small size studies addressing the profile of the inflammatory markers in OSA are available therefore we performed a meta-analysis.. Systematic review of medical literature was conducted using PubMed, Cochrane, and EMBASE databases from 1968 to 2011 by utilizing the key words obstructive sleep apnea, C-Reactive protein, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and Selectins. Inclusion criteria were: full text English articles; studies with adult population; reported values for at least one of the markers of interest; with at least two separate groups (subjects with OSA and control group); OSA was defined as AHI of ≥ 5/h.. Five hundred and twelve studies were reviewed for inclusion with 51 studies pooled for analysis (30 studies for CRP, 19 studies for TNF-α, 8 studies for ICAM, 18 studies for IL-6, six studies for VCAM and 5 studies for Selectins). The levels of inflammatory markers were higher in patients with OSA compared to control group. Standardized pooled Mean differences were calculated to be 1.77 for CRP, 1.03 for TNF-α, 2.16 for IL-6, 4.22 for IL-8, 2.93 for ICAM, 1.45 for Selectins and 2.08 for VCAM.. In this meta-analysis, the levels of systemic inflammatory markers were found to be higher in OSA patients compared to control subjects.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Cell Adhesion Molecules; Disease Progression; Female; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Polysomnography; Selectins; Sensitivity and Specificity; Severity of Illness Index; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Topics: Animals; Cattle; Cholic Acids; Humans; Inflammation; Interleukin-1beta; Interleukin-8; Materia Medica; Oropharynx; Otorhinolaryngologic Surgical Procedures; Postoperative Period; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Obstructive sleep apnea (OSA) and enhanced vascular inflammation coexist in patients with coronary artery disease (CAD). Continuous positive airway pressure (CPAP) is first-line treatment for OSA with daytime sleepiness. This analysis of data from the RICCADSA (Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea) trial investigated the effects of CPAP on inflammatory markers in patients with CAD and nonsleepy OSA.. This single-center, randomized, controlled, open-label trial enrolled consecutive revascularized patients with nonsleepy OSA (apnea-hypopnea index >15/h; Epworth Sleepiness Scale score <10). Levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were measured in blood samples taken at baseline (median 94 days after revascularization) and after 1 year of follow-up in patients randomized to CPAP or no-CPAP.. A total of 220 patients with analyzable blood samples at baseline and 1 year were included. Baseline IL-6 levels were significantly lower in the CPAP versus no-CPAP group (median 3.1 pmol/L [interquartile range 1.3-5.7] vs. 4.2 pmol/L [2.0-8.9], respectively; p = .005). At 1-year follow-up, median IL-6 levels were significantly reduced in both groups (to 2.2 pmol/L [1.2-3.9] in the CPAP group and to 2.2 [1.2-4.7] in no-CPAP group; both p < .001 vs. baseline). IL-8, hs-CRP, and TNF-α did not change significantly from baseline. There was no association between CPAP adherence and changes in inflammatory marker levels.. In patients with stable CAD and nonsleepy OSA, inflammatory biomarkers did not change significantly over time except for IL-6 levels, which reduced to the same extent in the CPAP and no-CPAP groups.. ClinicalTrials.gov, ID: NCT00519597; researchweb.org, VGSKAS-4731.

Topics: Aged; Biomarkers; C-Reactive Protein; Continuous Positive Airway Pressure; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Sleep Apnea, Obstructive; Sleep Stages; Tumor Necrosis Factor-alpha

To evaluate the correlation between concentrations of the proinflammatory cytokines monocyte chemotactic protein 1 (MCP-1), adiponectin, interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor (TNF) and patients with obstructive sleep apnea syndrome (OSAS). Repeated apnea attacks in patients with OSAS constitute a hypoxic condition, which induces tissue inflammation by mediation of these proinflammatory cytokines.. Radioimmunoassay analyses of nonrandomized controlled trial.. University-affiliated tertiary care hospital.. The study population comprised 59 patients who underwent the polysomnography.. Serum concentrations of MCP-1, adiponectin, IL-6, IL-8, and TNF, as well as body mass index and polysomnographic data, including apnea-hypopnea index (AHI) and lowest oxygen saturation.. The mean (SD) plasma level of MCP-1 in serum was increased in all patients with OSAS (P < .001), while adiponectin level was decreased in the patients with severe OSAS (6.88 [1.78] μg/mL) compared with normal controls (8.90 [2.63] μg/mL) (P = .006). Serum concentrations of IL-6, IL-8, and TNF did not exhibit any differences between patients with OSAS and normal controls. The correlation coefficient between plasma MCP-1 level and AHI was 0.62 and between adiponectin level and AHI was 0.66.. Our results suggest that plasma MCP-1 and adiponectin levels were different between patients with OSAS and normal controls. Adiponectin and MCP-1 may be prognostic factors for comparing patients with OSAS before and after treatment.

Topics: Adiponectin; Adult; Chemokine CCL2; Female; Humans; Interleukin-6; Interleukin-8; Male; Polysomnography; Radioimmunoassay; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Obstructive sleep apnea syndrome (OSA) is associated with systemic and upper airway inflammation. Pharyngeal inflammation has a potential role in upper airway collapse, whereas systemic inflammation relates to cardiovascular morbidity. However, the presence of an inflammatory involvement of lower airway has been poorly investigated.. The aim of the study was to demonstrate an inflammatory process at the bronchial level in patients with OSA and to analyze effects of continuous positive airway pressure (CPAP) application and humidification on bronchial mucosa.. The study was conducted by using sequential induced sputum for cell analysis and IL-8 production, nitric oxide exhalation measurement, and methacholine challenge before and after CPAP.. Bronchial neutrophilia and a high IL-8 concentration were observed in untreated OSA compared with controls (75% +/- 20% vs 43% +/- 12%, P < .05; and 25.02 +/- 9.43 ng/mL vs 8.6 +/- 3.7 ng/mL, P < .001, respectively). IL-8 in sputum supernatant was correlated to apnea hypopnea index (P < .01; r = 0.81). After 1 month of CPAP, this inflammatory pattern remained unchanged, and an increase in airway hyperresponsiveness (AHR) was observed (P < .001).. Obstructive sleep apnea syndrome is associated with bronchial inflammation. Our data demonstrate CPAP effect on the development of AHR, possibly facilitated by the pre-existing inflammation. Both issues should be evaluated during long-term CPAP use.. Results showing a spontaneous bronchial inflammation in OSA and the development of a CPAP-related AHR require a long-term follow-up to evaluate consequences on chronic bronchial obstruction.

Topics: Adult; Bronchi; Bronchial Hyperreactivity; Bronchitis; Bronchoconstrictor Agents; Continuous Positive Airway Pressure; Exhalation; Female; Humans; Interleukin-8; Male; Methacholine Chloride; Middle Aged; Neutrophils; Nitric Oxide; Respiratory Mucosa; Sleep Apnea, Obstructive; Sputum

Increasing evidence has noted that neuroinflammation contributes to the pathological processes of cognitive impairment of obstructive sleep apnea (OSA) patients. Interleukin (IL) -33/suppression of tumorigenicity 2 (ST2) signaling pathway plays well-defined roles in the inflammatory progression. The study aims to elucidate whether IL-33/ST2 signaling pathway plays a role in the cognitive dysfunction in patients with OSA via regulating neuroinflammation. We found that compared with control subjects, patients with OSA showed significantly elevated IL-33, ST2 and p65 nuclear factor-kappa B (NF-κB) levels in peripheral blood mononuclear cells (PBMCs) and inflammatory cytokines IL-6, IL-8 in serum, which were positively correlated with disease severity. Meanwhile, OSA patients exhibited a decline in Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores, suggesting mild cognitive impairment. Continuous positive airway pressure (CPAP) treatment for 12 weeks significantly decreased the expression of IL-33, ST2, p65NF-κB, IL-6 and IL-8, as well as improved cognitive function of OSA patients. Moreover, the IL-33/ST2 signaling was closely correlated with sleep respiratory parameters and cognitive dysfunction. To further explore the underlying mechanism of IL-33/ST2 signaling pathway, we stimulated human microglial clone 3 (HMC3) cells with lipopolysaccharide (LPS) to mimic neuroinflammatory response in vitro. The results showed that LPS treatment led to an increase in IL-33 and ST2 expression in a dose- dependent manner, along with an increased secretion of IL-6 and IL-8. Functional experiments showed that knockdown of IL-33 ameliorated LPS-induced neuroinflammation via suppressing NF-κB signaling. Overall, current findings suggest that IL-33/ST2 signaling participated in the cognitive impairment of OSA patients by promoting neuroinflammation via activating NF-κB signaling. These results may provide a novel therapeutic target for treating OSA- associated cognitive dysfunction.

Topics: Humans; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Lipopolysaccharides; Neuroinflammatory Diseases; NF-kappa B; Sleep Apnea, Obstructive

Adenotonsillar hypertrophy is the most common cause of pediatric obstructive sleep apnea (OSA). Although adenotonsillectomy considerably reduces OSA and systemic inflammation, whether and how systemic inflammation influences the effects of adenotonsillectomy on OSA has yet to be determined.. This study investigated the associations between changes in anatomical variables, % changes in subjective OSA-18 questionnaire scores, % changes in 11 polysomnographic parameters, and % changes in 27 systemic inflammatory biomarkers in 74 children with OSA.. Fifty-six (75.6%) boys and 18 (24.4%) girls with the mean age of 7.4 ± 2.2 years and apnea-hypopnea index (AHI) of 14.2 ± 15.9 events/h were included in the statistical analysis. The mean period between before and after adenotonsillectomy was 5.6 ± 2.6 months. After adenotonsillectomy, the OSA-18 score, eight of 11 polysomnographic parameters, and 20 of 27 inflammatory biomarkers significantly improved (all p < 0.005). Notably, there were significant associations between change in tonsil size and % change in AHI ( r = 0.23), change in tonsil size and % changes in interleukin-8 (IL-8) ( r = 0.34), change in tonsil size and % change in and IL-10 ( r = -0.36), % change in IL-8 and % change in C-C chemokine ligand 5 (CCL5) ( r = 0.30), and % change in CCL5 and % change in AHI ( r = 0.38) (all p < 0.005). Interestingly, % change in IL-8 and % change in CCL5 serially mediated the relationship between change in tonsil size and % change in AHI (total effect: β = 16.672, standard error = 8.274, p = 0.048).. These preliminary findings suggest that systemic inflammation is not only a complication of OSA but also that it mediates the surgical effects, which may open avenues for potential interventions to reduce tonsil size and OSA severity through the regulation of IL-8 and CCL5.

Topics: Child; Child, Preschool; Female; Humans; Inflammation; Interleukin-8; Male; Polysomnography; Sleep Apnea, Obstructive; Tonsillectomy

Obstructive sleep apnea (OSA) is a disease with great cardiovascular risk. Interleukin-8 (IL-8), an important chemokine for monocyte chemotactic migration, was studied under intermittent hypoxia condition and in OSA patients. Monocytic THP-1 cells were used to investigate the effect of intermittent hypoxia on the regulation of IL-8 by an intermittent hypoxic culture system. The secreted protein and mRNA levels were studied by means of enzyme-linked immunosorbent assay and RT/real-time PCR. The chemotactic migration of monocytes toward a conditioned medium containing IL-8 was performed by means of the transwell filter migration assay. Peripheral venous blood was collected from 31 adult OSA patients and RNA was extracted from the monocytes for the analysis of IL-8 expression. The result revealed that intermittent hypoxia enhanced the monocytic THP-1 cells to actively express IL-8 at both the secreted protein and mRNA levels, which subsequently increased the migration ability of monocytes toward IL-8. The ERK, PI3K and PKC pathways were demonstrated to contribute to the activation of IL-8 expression by intermittent hypoxia. In addition, increased monocytic IL-8 expression was found in OSA patients, with disease severity dependence and diurnal changes. This study concluded the monocytic IL-8 gene expression can be activated by intermittent hypoxia and increased in OSA patients.

Topics: Adult; Female; Gene Expression; Humans; Hypoxia; Interleukin-8; Male; Middle Aged; Monocytes; RNA, Messenger; Sleep Apnea, Obstructive; THP-1 Cells

Raftlin is a large, major lipid raft protein of cell membranes. Raftlin levels have not been previously examined in patients with obstructive sleep apnea (OSA). Our study aimed to evaluate the changes in raftlin, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNFα) values from the preoperative state to the third month postoperatively in patients undergoing expansion sphincter pharyngoplasty for OSA.. Of 60 patients, 10 patients had mild OSA (AHI 5-14), 10 moderate (AHI 15-29), 10 severe (AHI ≥ 30), and 30 with AHI < 5 formed a control group. Preoperatively and at 3 months post-operatively, IL-6, IL-8, TNFα, and raftlin values were measured.. Preoperatively, mean raftlin levels were 914.4 ± 62.7 pg/mL for controls, 910.0 ± 42.5 pg/mL in mild, 1000.5 ± 63.3 pg/mL in moderate, and 1386.3 ± 101.4 pg/mL in severe groups, with moderate and severe groups significantly elevated compared to controls (p < 0.001). Preoperatively to 3 months post-operatively, raftlin levels decreased significantly in each OSA group (p < 0.05). Levels of IL-6, IL-8 and TNFα followed similar patterns at baseline and after surgical intervention.. Raftlin levels at the third postoperative month decreased significantly compared with preoperative levels in parallel with other markers of inflammation.

Topics: Adult; Female; Humans; Interleukin-6; Interleukin-8; Male; Membrane Proteins; Middle Aged; Patient Acuity; Pharynx; Postoperative Period; Preoperative Period; Sleep Apnea, Obstructive; Treatment Outcome; Tumor Necrosis Factor-alpha

Obstructive sleep apnea (OSA) is associated with recurrent obstruction, subepithelial edema, and airway inflammation. The resultant inflammation may influence or be influenced by the nasal microbiome.. To evaluate whether the composition of the nasal microbiota is associated with obstructive sleep apnea and inflammatory biomarkers.. Two large cohorts were used: 1) a discovery cohort of 472 subjects from the WTCSNORE (Seated, Supine and Post-Decongestion Nasal Resistance in World Trade Center Rescue and Recovery Workers) cohort, and 2) a validation cohort of 93 subjects rom the Zaragoza Sleep cohort. Sleep apnea was diagnosed using home sleep tests. Nasal lavages were obtained from cohort subjects to measure: 1) microbiome composition (based on 16S rRNA gene sequencing), and 2) biomarkers for inflammation (inflammatory cells, IL-8, and IL-6). Longitudinal 3-month samples were obtained in the validation cohort, including after continuous positive airway pressure treatment when indicated.. In both cohorts, we identified that: 1) severity of OSA correlated with differences in microbiome diversity and composition; 2) the nasal microbiome of subjects with severe OSA were enriched with Streptococcus, Prevotella, and Veillonella; and 3) the nasal microbiome differences were associated with inflammatory biomarkers. Network analysis identified clusters of cooccurring microbes that defined communities. Several common oral commensals (e.g., Streptococcus, Rothia, Veillonella, and Fusobacterium) correlated with apnea-hypopnea index. Three months of treatment with continuous positive airway pressure did not change the composition of the nasal microbiota.. We demonstrate that the presence of an altered microbiome in severe OSA is associated with inflammatory markers. Further experimental approaches to explore causal links are needed.

Topics: Adult; Biomarkers; Female; Humans; Interleukin-6; Interleukin-8; Male; Microbiota; Middle Aged; Nasal Cavity; Nasal Lavage Fluid; RNA, Ribosomal, 16S; Severity of Illness Index; Sleep Apnea, Obstructive

BACKGROUND Obstructive sleep apnea (OSA) is associated with many cardiovascular disorders. Intermittent hypoxia (IH) is a key pathological hallmark of OSA. This study was conducted to evaluate the potential therapeutic effects and the associated mechanisms of adiponectin (APN) on IH induced human adult cardiac myocytes (HACMs) injury. MATERIAL AND METHODS HACMs were exposed to normoxia or IH (1% to 21% O₂) using a novel cell culture bio-reactor with gas-permeable membranes. Cell viability was detected by Cell Counting Kit-8 assay. Cell membrane integrity was assessed by the detection of lactate dehydrogenase (LDH) release. Cell apoptosis was analyzed by flow cytometry. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were determined using specific assay kits. P-AMPK (AMP-activated protein kinase), p-LKB1, and p-p65 protein levels were measured by western blotting. Pro-inflammatory factors including interleukin (IL)-1β, IL-6, IL-8 expressions were detected by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. RESULTS The results showed that APN had no cytotoxic to HACMs. Compared with the control group, HACMs cell viability significantly decreased, LDH release increased and cell apoptosis increased in the IH group. The levels of IL-1β, IL-6, IL-8, MDA, and p-p65 were higher, while the levels of SOD, GSH-Px, p-AMPK, and p-LKB1 were lower in HACMs cells in the IH group than that in the control group. However, APN treatment significantly rescued these effects compared with the IH group in a dose-dependent manner. CONCLUSIONS In conclusion, these results indicated that APN protected against IH induced HACMs injury possibly mediated by AMPK and NF-κB pathway.

Topics: Adiponectin; Adult; Apoptosis; Blotting, Western; Cell Hypoxia; Glutathione Peroxidase; Heart Injuries; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; L-Lactate Dehydrogenase; Malondialdehyde; Myocytes, Cardiac; Primary Cell Culture; Sleep Apnea, Obstructive; Superoxide Dismutase

We explored the effects of RNA interference-mediated silencing of TLR4 gene on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS) with hypertension in a rat model. Systolic blood pressure of caudal artery and physiological changes were observed when establishing rat models of OSAS with hypertension. Mature rat adipocytes were induced from separated and cultured primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and negative control (NC) siRNA group were established. Expressions of TLR4 mRNA of adipocytes were examined after silenced by siRNA by quantitative real-time polymerase chain reaction (qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), expressions of inflammatory cytokines, and adipocytokines of adipocytes were detected. Blood pressure in rat caudal artery was higher in the intermittent hypoxia group than that of the blank control group by 29.87 mmHg, and cardiocytes in the former group showed physiological changes, which indicated successful establishment of rat models of OSAS with hypertension. Red particles could be seen in mature rat adipocytes when stained with Oil Red O. Transfection of TLR4 mRNA was significantly suppressed in the TLR4 siRNA group, which didn't happen in the untransfected control group. Rats in the TLR4 siRNA group had significantly reduced expressions of such inflammatory cytokines as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and such adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the untransfected control group. RNA interference-mediated silencing of TLR4 gene could regulate occurrence and development of OSAS with hypertension in rats by downregulating expressions of adipocytokines.

Topics: Adipocytes; Adipokines; Adiponectin; Animals; Cytokines; Disease Models, Animal; Gene Expression Regulation; Humans; Hypertension; Interleukin-6; Interleukin-8; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Rats; RNA, Small Interfering; Sleep Apnea, Obstructive; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

The goal of this study was to assess the relationship between the severity of obstructive sleep apnoea (OSA) and the levels of carcinogenesis- and tumour growth-related biomarkers in patients with cutaneous melanoma.This multicentre observational study included patients who were newly diagnosed with melanoma. The patients were classified as non-OSA (apnoea-hypopnoea index (AHI) 0-5 events·h

Topics: Adult; Aged; Biomarkers, Tumor; Carcinogenesis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypoxia; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Melanoma; Middle Aged; S100 Calcium Binding Protein beta Subunit; Skin Neoplasms; Sleep Apnea, Obstructive; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A

Biomarkers of atherosclerosis (pro-inflammatory cytokines and acute phase reactants) are elevated in children with obstructive sleep apnea (OSA). However, their association with cardiovascular endpoints in children are not understood. We hypothesized that biomarkers of atherosclerosis in children with OSA correlate with pulse transit time (PTT), a surrogate measure of vascular stiffness, with some positively influencing and others negatively influencing PTT.. Children with OSA and matched controls were recruited to the study. Pro-inflammatory cytokines and acute phase reactants were measured at 6:00 pm and 6:00 am. Polysomnography with beat-to-beat blood pressure was performed. PTT during wakefulness and stage 2 sleep was calculated. Diurnal variation of biomarkers and their associations with PTT was estimated. Factor analysis was used to determine the effect of groups of cytokines on PTT.. One hundred fifty-five children participated in the study; 90 were healthy controls and 65 had OSA. Children with OSA exhibited a different diurnal variation of biomarkers than healthy controls, with pro-inflammatory cytokines peaking in the morning and acute phase reactants peaking in the afternoon. Structural equation modeling demonstrated that interleukins 6 and 8, tumor necrosis factor-α, and sCD40L had a shortening effect, while serum amyloid A, C-reactive protein, and adiponectin had a prolonging effect on PTT. As a result, there was no difference in PTT between the two groups.. The differential relationships of acute phase reactants and pro-inflammatory cytokines with PTT suggest that in children with OSA, these mediators may have opposing actions to maintain cardiovascular homeostasis.

Topics: Adiponectin; Adolescent; Biomarkers; Blood Pressure; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Cytokines; Female; Homeostasis; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Polysomnography; Pulse Wave Analysis; Serum Amyloid A Protein; Sleep; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha; Wakefulness

Obstructive sleep apnoea (OSA) is frequently observed in severe asthma but the causal link between the 2 diseases remains hypothetical. The role of OSA-related systemic and airway neutrophilic inflammation in asthma bronchial inflammation or remodelling has been rarely investigated. The aim of this study was to compare hallmarks of inflammation in induced sputum and features of airway remodelling in bronchial biopsies from adult patients with severe asthma with and without OSA.. An overnight polygraphy was performed in 55 patients referred for difficult-to-treat asthma, who complained of nocturnal respiratory symptoms, poor sleep quality or fatigue. We compared sputum analysis, reticular basement membrane (RBM) thickness, smooth muscle area, vascular density and inflammatory cell infiltration in bronchial biopsies.. In total, 27/55 patients (49%) had OSA diagnosed by overnight polygraphy. Despite a moderate increase in apnoea-hypopnoea index (AHI; 14.2 ± 1.6 event/h [5-35]), the proportion of sputum neutrophils was higher and that of macrophages lower in OSA than non-OSA patients, with higher levels of interleukin 8 and matrix metalloproteinase 9. The RBM was significantly thinner in OSA than non-OSA patients (5.8 ± 0.4 vs. 7.8 ± 0.4 μm, p<0.05). RBM thickness and OSA severity assessed by the AHI were negatively correlated (rho = -0.65, p<0.05). OSA and non-OSA patients did not differ in age, sex, BMI, lung function, asthma control findings or treatment.. Mild OSA in patients with severe asthma is associated with increased proportion of neutrophils in sputum and changes in airway remodelling.

Topics: Adolescent; Adult; Aged; Asthma; Case-Control Studies; Female; Humans; Inflammation; Interleukin-8; Macrophages; Male; Matrix Metalloproteinase 9; Middle Aged; Neutrophils; Prospective Studies; Respiratory System; Sleep Apnea, Obstructive; Sputum; Young Adult

Obstructive sleep apnoea (OSA) is associated with pharyngeal inflammation, but the coexistence of systemic inflammation is controversial. This study investigated whether local and systemic inflammatory biomarkers are related in patients with OSA. An uncontrolled extension to the study assessed the response to effective treatment.We recruited 89 patients with OSA (apnoea/hypopnoea index (AHI) ≥5 events·h

Topics: Adolescent; Adult; Anthropometry; Biomarkers; Case-Control Studies; CD4-Positive T-Lymphocytes; Continuous Positive Airway Pressure; Female; Flow Cytometry; Humans; Immunoassay; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Sleep Apnea, Obstructive; Snoring; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

Obstructive sleep apnea (OSA) is characterized by intermittent airway obstruction and systemic hypoxia during sleep, which can contribute to an increase in reactive oxygen species, vascular remodeling, vasoconstriction and ultimately cardiovascular disease. Continuous positive airway pressure (CPAP) is a clinical therapy that maintains airway patency and mitigates several symptoms of OSA. However, it is currently unknown whether CPAP therapy also reduces the overall inflammatory potential in the circulation; to address this in an unbiased manner, we applied a novel endothelial biosensor approach, the serum cumulative inflammatory potential (SCIP) assay.. We studied healthy controls (n = 7), OSA subjects receiving no treatment, (OSA controls) (n = 7) and OSA subjects receiving CPAP for 3 months (n = 8). Serum was obtained from OSA subjects before and after CPAP or no treatment. A battery of quantitative and functional assays was performed to assess the serum inflammatory potential, in terms of endothelial responses. For the SCIP assay, human coronary artery endothelial cells (hCAECs) were incubated with 5% serum in media from individual subjects for 4 h. qPCR was performed to assess endothelial inflammatory transcript (ICAM-1, VCAM-1, IL-8, P-selectin, CCL5, and CXCL12) responses to serum. Additionally, transendothelial resistance was measured in serum-incubated hCAECs following leukocyte challenge.. hCAECs exhibited significant increases in VCAM-1, ICAM-1, IL-8 and P-selectin mRNA when incubated with serum from OSA patients compared to serum from healthy control subjects. Furthermore, compared to no treatment, serum from CPAP-treated individuals was less potent at inducing inflammatory gene expression in the SCIP assay. Similarly, in a leukocyte adhesion assay, naïve cells treated with serum from patients who received CPAP exhibited improved endothelial barrier function than cells treated with OSA control serum.. OSA results in greater serum inflammatory potential, thereby driving endothelial activation and dysfunction.

Topics: Adult; Biosensing Techniques; Case-Control Studies; Cell Adhesion; Cohort Studies; Continuous Positive Airway Pressure; Coronary Vessels; Endothelial Cells; Humans; Hypoxia; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Leukocytes; Male; Middle Aged; P-Selectin; Risk Factors; Sleep Apnea, Obstructive; Vascular Cell Adhesion Molecule-1

Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD). Enhanced vascular inflammation is implicated as a pathophysiologic mechanism but obesity is confounding. We aimed to address the association of OSA with inflammatory biomarkers in a nonobese cohort of revascularized patients with CAD and preserved left ventricular ejection fraction.. Cross-sectional analysis of baseline investigations of a randomized controlled trial.. Clinic-based.. There were 303 nonobese patients with CAD, of whom 213 with OSA (apnea-hypopnea index [AHI] ≥15 events/h) and 90 without OSA (AHI < 5 events/h). Obese patients with CAD and OSA (N = 105) were chosen as an additional control group.. None.. Circulating levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α were assessed in relation to OSA diagnosis based on AHI ≥ 15 events/h as well as oxygen desaturation index (ODI) ≥ 5 events/h.. Nonobese patients with OSA had significantly higher levels of hs-CRP and IL-6 than those without OSA. The values did not differ significantly between obese and nonobese patients with OSA. In bivariate regression analysis, AHI ≥ 15 events/h was associated with all four biomarkers but not so in the multivariate model after adjustment for confounders. ODI ≥ 5 events/h was associated with hs-CRP (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.13-1.99) and IL-6 (OR 1.30; 95% CI 1.05-1.60) in multivariate analysis.. OSA with ODI ≥ 5 was independently associated with increased inflammatory activity in this nonobese CAD cohort. The intermittent hypoxemia, rather than the number of apneas and hypopneas, appears to be primarily associated with enhanced inflammation.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Odds Ratio; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Chronic obstructive pulmonary disease (COPD) concomitant with obstructive sleep apnea (OSA) is known as overlap syndrome. It has an increased rate of hospitalization due to COPD exacerbation which is believed to indicate a worsening of the underlying chronic airway inflammation. Therefore, the aim of this prospective study was to explore whether OSA exacerbates airway inflammation in subjects with COPD by examining the bronchoalveolar lavage (BAL) fluid.. This prospective study included 47 patients with overlap syndrome and 28 patients with moderate-to-severe stage stable COPD. Twenty-five patients with overlap syndrome adhered to the continuous positive airway pressure (CPAP) treatment; the remaining patients either refused CPAP treatment or discontinued it within two weeks owing to adverse effects or other reasons. BAL fluid was collected from all subjects for the evaluation of cell numbers and tumor necrosis factor alpha (TNFα) and interleukin-8 (IL-8) levels.. The BAL fluid of patients with overlap syndrome showed a significantly increased proportion of neutrophils and higher TNFα concentration and IL-8 levels than that of COPD patients; however, the serum CRP levels were not significantly different. An association was found between the percentage of neutrophils and the TNFα concentration and IL-8 levels. Moreover, the TNFα concentration was significantly correlated with the percentage of nighttime spent with oxygen saturation less than 90%. After CPAP treatment, airway inflammation was found to decrease significantly.. OSA exacerbates airway inflammation in COPD patients. CPAP treatment can improve nocturnal hypoxemia and decrease airway inflammation.

Topics: Aged; Bronchoalveolar Lavage Fluid; C-Reactive Protein; Continuous Positive Airway Pressure; Female; Humans; Interleukin-8; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Intermittent hypoxia (IH)-induced activation of pro-inflammatory pathways is a major contributing factor to the cardiovascular pathophysiology associated with obstructive sleep apnea (OSA). Obesity is commonly associated with OSA although it remains unknown whether adipose tissue is a major source of inflammatory mediators in response to IH. The aim of this study was to test the hypothesis that IH leads to augmented inflammatory responses in human adipocytes when compared to cells of non-adipocyte lineages.. Human primary subcutaneous and visceral adipocytes, human primary microvascular pulmonary endothelial cells (HUMEC-L) and human primary small airway epithelial cells (SAEC) were exposed to 0, 6 or 12 cycles of IH or stimulated with tumor necrosis factor (TNF)-α. IH led to a robust increase in NF-κB DNA-binding activity in adipocytes compared with normoxic controls regardless of whether the source of adipocytes was visceral or subcutaneous. Notably, the NF-κB response of adipocytes to both IH and TNF-α was significantly greater than that in HUMEC-L and SAEC. Western blotting confirmed enhanced nuclear translocation of p65 in adipocytes in response to IH, accompanied by phosphorylation of I-κB. Parallel to p65 activation, we observed a significant increase in secretion of the adipokines interleukin (IL)-8, IL-6 and TNF-α with IH in adipocytes accompanied by significant upregulation of mRNA expression. PCR-array suggested profound influence of IH on pro-inflammatory gene expression in adipocytes.. Human adipocytes demonstrate strong sensitivity to inflammatory gene expression in response to acute IH and hence, adipose tissue may be a key source of inflammatory mediators in OSA.

Topics: Active Transport, Cell Nucleus; Adipocytes, White; Adipokines; Cardiovascular Diseases; Cell Hypoxia; Cells, Cultured; DNA; Gene Expression Regulation; Humans; I-kappa B Proteins; Inflammation Mediators; Interleukin-6; Interleukin-8; Phosphorylation; RNA, Messenger; Sleep Apnea, Obstructive; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) show a high prevalence of erectile dysfunction (ED). Although the underlying pathogenesis is still unknown, endothelial dysfunction, induced by inflammatory cytokines, chemokines, and adhesion molecules, has been proposed as a possible mechanism. The aim of this study was to assess whether OSAHS is associated with activation of the inflammatory cytokine system in patients with ED compared to the matched OSAHS patients with normal sexual function. Thirty-one patients with severe OSAHS and ED were included. Fifteen patients with severe OSAHS and without ED served as controls. Serum concentrations of high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-a), interleukin-6 (IL-6), interleukin-8 (IL-8), and adiponectin were measured after the diagnostic polysomnography. We found that hsCRP levels were significantly elevated in OSAHS patients with ED compared to controls. Similarly, TNF-a levels, IL-6, and IL-8 were elevated in OSAHS patients with ED compared to controls. Serum adiponectin levels were lower in OSAHS-ED patients, but the difference did not reach statistical significance. The presence of ED in patients with severe OSAHS is associated with elevated levels of inflammatory markers, underlining a possible involvement of endothelial dysfunction in the pathogenesis of ED.

Topics: Adiponectin; Adult; Body Mass Index; C-Reactive Protein; Cytokines; Erectile Dysfunction; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Surveys and Questionnaires; Tumor Necrosis Factor-alpha

Childhood obstructive sleep apnea syndrome (OSAS) is associated with an elevation of inflammatory markers such as C-reactive protein (CRP) that correlates with specific morbidities and subsides following intervention. In adults, OSAS is associated with activation of the transcription factor nuclear factor kappa B (NF-kB). We explored the mechanisms underlying NF-kB activation, based on the hypothesis that specific NF-kB signaling is activated in children with OSAS.. Adenoid and tonsillar tissues from children with OSAS and matched controls were immunostained against NF-kB classical (p65 and p50) and alternative (RelB and p52) pathway subunits, and NF-kB-dependent cytokines: interleukin (IL)- 1α, IL-1β, tumor necrosis factor-α, and IL-8). Serum CRP levels were measured in all subjects. NF-kB induction was evaluated by a luciferase-NF-kB reporter assay in L428 cells constitutively expressing NF-kB and in Jurkat cells with inducible NF-kB expression. p65 translocation to the nucleus, reflecting NF-kB activation, was measured in cells expressing fluorescent NF-kB-p65-GFP (green fluorescent protein).. Sleep research laboratory.. Twenty-five children with OSAS and 24 without OSAS.. N/A.. Higher expression of IL-1α and classical NF-kB subunits p65 and p50 was observed in adenoids and tonsils of children with OSAS. Patient serum induced NF-kB activity, as measured by a luciferase-NF-kB reporter assay and by induction of p65 nuclear translocation in cells permanently transfected with GFP-p65 plasmid. IL-1β showed increased epithelial expression in OSAS tissues.. Nuclear factor kappa B is locally and systemically activated in children with obstructive sleep apnea syndrome. This observation may motivate the search for new anti-inflammatory strategies for controlling nuclear factor kappa B activation in obstructive sleep apnea syndrome.

Topics: Adenoids; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Female; Humans; Inflammation; Interleukin-1alpha; Interleukin-1beta; Interleukin-8; Male; NF-kappa B; Palatine Tonsil; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Detection and significance of CXCL8, IL-10 in serum and tissue of the patients' with OSHAS.. All subjects take serum CXCL8 and IL-10 levels were determined by ELISA. All subjects take the same position of the soft palate tissues in the operation. CXCL8 and IL-10 in the tissue expression was measured by immune histochemistry.. (1) Serum CXCL8 levels in OSHAS is higher than that in the control group (P < 0.05). (2) Serum IL-10 levels in OSHAS is lower than that in the control group (P < 0.05). (3) Tissues CXCL8 expression was correlated with serum CXCL8 (r = 0.474, P < 0.05). (4) Tissues IL-10 expression wasn't any correlated with serum IL-10. (5) Tissues IL-10 expression was correlated with tissues CXCL8 (r = 0.482, P < 0.05).. OSAHS may be a disease associated with inflammation, and closely relate with CXCL8 and IL-10.

Topics: Adult; Case-Control Studies; Female; Humans; Interleukin-10; Interleukin-8; Male; Middle Aged; Sleep Apnea, Obstructive

The relationship between obstructive sleep apnea (OSA) and atherosclerosis-related inflammation has been poorly investigated, particularly focusing on functional responses of immune cells playing a key role in atherogenesis and in comparison with control groups with similar cardiovascular risk factors which are known to be themselves associated with inflammation. We sought to determine cellular tumor necrosis factor-alpha (TNF-α) production from peripheral blood mononuclear cells (PBMCs) and interleukin (IL)-8 release from neutrophils (PMNs) in patients studied for suspected OSA.. Thirty-six consecutive patients who underwent a nocturnal complete cardiorespiratory evaluation for suspected OSA were initially evaluated. Serum, PBMCs, and PMNs were isolated (at baseline and after 12 weeks) from patients with apnea-ipopnea index (AHI) >20 (OSA group, n = 16) and from control patients with AHI <5 (nonOSA group, n = 11). All patients continued the same pharmacological therapy for 12 weeks; the OSA group was additionally treated with nocturnal continuous positive-airway-pressure ventilation (cPAP).. The two groups had similar clinical characteristics (prevalence of hypertension, dyslipidemia, diabetes, and cardio-metabolic therapies) except for obesity. Resting and stimulated TNF-α production from PBMCs and IL-8 release from PMNs were similar in the two groups. Serum cytokines resulted within the normal range. In the OSA group, cPAP was not associated with changes in cellular responses.. In patients showing similar prevalence of major cardiovascular risk factors and cardio-metabolic therapies, differing for the presence or absence of OSA, cytokine productions from PBMC and PMN were similar and were not modified during cPAP therapy. Studies designed to investigate OSA-associated inflammation should carefully match the control group subjects.

Topics: Adult; Aged; Continuous Positive Airway Pressure; Cytokines; Female; Humans; Interleukin-8; Male; Middle Aged; Monocytes; Neutrophils; Reference Values; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

To study the systemic production of inflammatory factors and activation of transcription factor nuclear factor kappa B (NF-κB) in response to different levels of intermittent hypoxia and time.. A total of 160 male Wistar rats were divided randomly into five groups. The first three groups were exposed to 5%, 7.5% and 10% intermittent hypoxia (referred to as IH-1, IH-2, and IH-3 respectively), the fourth group were subjected to 10% sustained hypoxia (abbreviated as SH), and the control group were exposed to normal oxygen (designated SC). At the second, fourth, sixth, and eighth week, eight rats in each group were sacrificed to collect serum. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum concentration of tumour necrosis factor alpha (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6) and interleukin-10 (IL-10). Western blot was used to detect the protein levels of the phosphorylated NF-κB P65 in the nucleus of arterial endothelial cells.. In all three IH groups serum levels of TNF-α, IL-8 and IL-6 showed consecutive increment from onset to the 6th week under intermittent hypoxia; the levels of TNF-α and IL-8 dropped slightly on the 8th week, whereas those of IL-6 continued to increase. The levels of IL-10 decreased and reached nadir at the 6th week of intermittent hypoxia treatment. The inflammatory response was the most pronounced in the 6th week, at which time the TNF-α, IL-8 and IL-6 levels in IH groups were significantly higher than in the SC and SH group (F = 30.04, 11.77, 18.589; p <0.05). IL-10 levels were significantly lower than the SC and SH group (F = 10.403, p <0.05). Levels of TNF-α and IL-8 in the IH-1 group were significantly higher than those in the IH-3 group (F = 1.20, 34.68; p = 0.049, 0.046). Protein levels of phosphorylated NF-κB P65 in endothelial cells collected from thoracic aorta in all three IH groups were significantly higher than those in SC and SH groups (F = 63.136, p = 0.01). A close correlation was identified between NF-κB p65 phosphorylation and the levels of TNF-α, IL-8, IL-6 and IL-10 (p = 0.01).. The inflammatory response, manifested by serum levels of inflammatory factors and nuclear accumulation of activated NF-κB P65, was more serious in the IH group than in the SH and control group, and was dependent on hypoxia levels. This reaction increased initially and then decreased, which indicates the presence of compensatory mechanisms and an adaptive response to such stressors in the body. Notably, the correlation of NFκB activation to production of inflammatory factors under intermittent hypoxia implies an important role of this transcription factor in inflammation-induced cardiovascular damage occurring during obstructive sleep apnoea (OSA), which has a typical breathing pattern of intermittent hypoxia.

Topics: Animals; Blood Gas Analysis; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Hypoxia; Interleukin-10; Interleukin-6; Interleukin-8; Interleukins; Male; NF-kappa B; Rats; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

The recurrent hypoxic stress that characterizes obstructive sleep apnea (OSA) seems to play a role in the increased adherence of neutrophils to endothelial cells as well as in the resulting migration of the former to the inflamed area. Intercellular adhesion molecule 1 (ICAM-1) and interleukin (IL)-8 are markers widely used in OSA studies to investigate inflammation. The aim of this study was to measure ICAM-1 and IL-8 levels in the breath condensate and in the plasma and inflammatory cells in the induced sputum of 12 obese OSA (OO) patients, 10 nonobese OSA (NOO) patients, 10 obese non-OSA (ONO) subjects, and 8 healthy subjects (HS) using a specific enzyme immunoassay (EIA) kit. A significant increase in both plasma and exhaled IL-8 and ICAM concentrations and percentage neutrophils was observed in the induced sputum of obese OSA patients, non-obese OSA patients, and obese non-OSA subjects compared with healthy subjects. However, although these inflammatory markers were found to follow an upward trend in obese OSA patients no difference was observed in both either non-obese OSA patients and obese non-OSA subjects. Finally, a significant positive correlation was found to occur among IL-8, ICAM-1, and sputum neutrophils, as well as across the apnea-hypopnoea index (AHI), TST 90%, body mass index (BMI), and neck circumference. The data obtained confirm the occurrence of an ICAM- and IL-8-mediated neutrophilic airway inflammation in both OSA and obese patients. The degree of inflammation, which seems to worsen in cases of comorbidity (OSA and obesity), is likely to be responsible for the increased risk of developing cardiovascular events observed in these subjects, and therefore, it deserves to be elucidated even more.

Topics: Adult; Aged; Asthma; Breath Tests; Cell Count; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Middle Aged; Neutrophils; Obesity; Sleep Apnea, Obstructive; Sputum

To evaluate serum cytokine concentrations in children with and without obstructive sleep apnoea (OSA) and to investigate the effects of OSA treatment on cytokines.. Consecutive children with habitual snoring and symptoms suggestive of OSA were recruited. They completed a sleep apnoea symptom questionnaire, underwent physical examination and overnight polysomnography (PSG). OSA was diagnosed if obstructive apnoea index (OAI) >1. A blood sample was collected for analysis of IL-6, IL-8, and TNF-alpha after PSG.. One hundred forty-two children (97 males) with a median (IQR) age of 11.1 years (9.0-12.8) were recruited. The commonest presenting symptoms were nocturnal mouth breathing, prone sleeping position and poor attention at school. Forty-seven children were found to have OSA and they had higher serum IL-6 [0.1 (0.1-0.4) vs 0.1 (0.1-0.1) pg/mL, P = 0.001] and IL-8 [1.7 (1.0-2.3) vs 1.3 (0.9-1.7) pg/mL, P = 0.029] concentrations compared to their non-OSA counterparts. Multiple regression analysis indicated that OAI was significantly associated with both IL-6 (r = 0.351, P <0.001) and IL-8 (r = 0.266, P = 0.002). Sixteen children underwent treatment and there was significant reduction in mean (SD) serum IL-8 after intervention [pre vs post levels of 1.9 (1.0) vs 1.1 (0.6) pg/mL, P = 0.001] independent of weight loss.. Children with OSA had elevated levels of pro-inflammatory cytokines that normalised following treatment suggesting that the inflammatory response is potentially reversible. Early detection and intervention may be beneficial.

Topics: Child; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Male; Polysomnography; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

To evaluate a range of inflammatory measures in children with obstructive sleep apnoea (OSA).. In total, 44 children with polysomnographically defined OSA (30 boys; mean age: 7.3 +/- 3.7 years) and 69 control subjects (44 boys; mean age: 7.6 +/- 4 years) were recruited. Controls were screened for symptoms of OSA by questionnaire at the time of elective surgery that was unrelated to the upper airway. Blood samples were analysed for C-reactive protein, and cytokines IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, GM-CSF, IFN-gamma and TNF-alpha.. The majority of the children had mild OSA (32/44). Children with OSA (respiratory disturbance index 5.3 +/- 6.5 events/h) had significantly higher IFN-gamma and IL-8 levels than controls (P < 0.001 and 0.003, respectively), although correction for age, sex and body mass index reduced these differences (IFN-gammaP = 0.002, and IL-8 P = 0.051). There were no significant correlations between inflammatory measures and body mass index, respiratory disturbance index, or other sleep, desaturation, or arousal parameters including respiratory or spontaneous arousal indices, desaturation index or severity, sleep efficiency, or apnoea/hypopnoea duration in the OSA group.. Children with OSA, even of mild severity, have significantly elevated IFN-gamma levels and a trend towards elevated IL-8 levels compared with asymptomatic controls, consistent with a pro-inflammatory effect of OSA. These changes seen in mild OSA may precede changes in other pro-inflammatory cytokines found in studies of adults with more severe and long-standing disease, implying a potential benefit from early disease identification and intervention.

Topics: Adolescent; Body Mass Index; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Cytokines; Humans; Inflammation; Inflammation Mediators; Interferon-gamma; Interleukin-8; Male; Polysomnography; Severity of Illness Index; Sleep Apnea, Obstructive; Surveys and Questionnaires; Tumor Necrosis Factor-alpha

Circulating nuclear factor-kappaB (NF-kappaB)-dependent genes, particularly tumor necrosis factor-alpha (TNF-alpha), are elevated in obstructive sleep apnea syndrome (OSAS) and likely contribute to cardiovascular disease. Furthermore, TNF-alpha is associated with excessive daytime sleepiness. We investigated the predictors of TNF-alpha and related genes in large, well-selected cohorts of subjects with OSAS and control subjects.. We performed a prospective study of 30 subjects who did not have OSAS (22 nonsleepy normal control subjects and 8 sleepy nonapneic subjects who snored), 36 subjects with mild to moderate OSAS, and 31 subjects with severe OSAS; all subjects were male. Groups were matched for age, body mass index, and other relevant variables. Subjects had no other disease and were not regularly taking medication. All had serum for TNF-alpha and related assays drawn after polysomnography. A total of 49 suitable subjects were treated with continuous positive airway pressure (CPAP); sleep studies together with serum assays were repeated 6 wk later.. TNF-alpha levels were higher in subjects with OSAS than in subjects without OSAS (p < 0.001). In multivariate analysis, TNF-alpha was independently associated with the desaturation index (r = 0.399, p < 0.001), Epworth Sleepiness Score (r = 0.243, p = 0.005), and cholesterol (r = 0.216, p = 0.018). Furthermore, TNF-alpha levels were higher in sleepy nonapneic subjects who snored than in normal control subjects (p = 0.002) but lower than in subjects with OSAS (p = 0.03). CPAP therapy lowered TNF-alpha levels (p = 0.004). Another NF-kappaB-dependent cytokine, interleukin-8 (IL-8), showed similar differences between groups and after CPAP therapy, but a range of other mediators of inflammation, including IL-1, IL-6, IL-10, and IL-12, showed no differences.. Intermittent hypoxia is the strongest predictor of TNF-alpha levels, supporting a role for inflammation in the cardiovascular pathophysiology of OSAS. Furthermore, TNF-alpha levels are independently associated with excessive daytime sleepiness.

Topics: Adult; Aged; Continuous Positive Airway Pressure; Female; Humans; Hypoxia; Interleukin-8; Interleukins; Male; Middle Aged; Multivariate Analysis; NF-kappa B; Prospective Studies; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality and many other physiological and immunological disorders. An increase in hypoxia due to OSA may cause generation of reactive oxygen species (ROS). ROS are toxic to biomembranes and may lead to peroxidation of lipids. An increase in systemic biomarkers of inflammation and oxidative stress has been found in patients with OSA. The first aim of this study was to test the hypothesis that OSA is linked to increased oxidative stress (lipid peroxidation) and decreased antioxidant defense [superoxide dismutase (SOD)]. The second aim was to measure the serum levels of neutrophil chemokines [interleukin-8 (IL-8)], and granulocyte chemotactic protein-2 (GCP-2) in OSA patients. Twenty five patients with severe OSA and 17 healthy subjects were recruited. IL-8 and GCP-2 were measured in the serum by a specific enzyme immunoassay kit. Oxidative stress level was quantitated by measurement of thiobarbituric acid reactive substances. SOD enzymatic activity was measured by purely chemical system based on NAD(P)H oxidation. Mean SOD and lipid peroxidation concentrations of patients were not significantly different from those of control subjects (0.29+/-0.015 vs 0.31+/-0.01 U/ml and 4.64+/-0.57 vs 4.62+/-0.54 mmol/ml, respectively). Higher concentrations of IL-8 and GCP-2 were found in OSA patients (198.8+/-4.76 vs 180.83+/-3.38 and 383.34+/-46.19 vs 218+/-13.16 pg/ml, respectively, p<0.005). The present study does not support the hypothesis that OSA is linked to increased oxidative stress and decreased antioxidant defense. On the other hand, it suggests that systemic inflammation characterizes OSA patients.

Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cell Membrane; Chemokine CXCL6; Female; Humans; Immunoenzyme Techniques; Interleukin-8; Lipid Peroxides; Male; Middle Aged; Pilot Projects; Polysomnography; Reactive Oxygen Species; Risk Factors; Severity of Illness Index; Sleep Apnea, Obstructive; Superoxide Dismutase

Patients with obstructive sleep apnea treated with nasal continuous positive airway pressure (CPAP) often complain of nasal side effects. We studied patients before and after initiation of nasal CPAP to see how treatment affected nasal function and markers of nasal inflammation. We searched for pretreatment findings that might help to predict noncompliance.. Nasal symptom scores, nasal flow by anterior rhinomanometry, mediator levels (intercellular adhesion molecule-1, interleukin-6, interleukin-8 and interleukin-13), and nasal scrapes for cytology were obtained at baseline and monthly for up to 3 months of nasal CPAP therapy. Compliance was assessed from the patient's report and by recording hours of usage for up to 19 months of follow-up.. Thirty-eight patients with newly diagnosed obstructive sleep apnea were classified as having no rhinitis (42%), allergic rhinitis (37%), or nonallergic rhinitis (21%). There was no significant difference in compliance in patients with and without rhinitis. Compliant and noncompliant patients showed no significant differences in their baseline nasal symptom scores, nasal flow, and mediator levels. Nasal neutrophil counts before treatment were greater in noncompliant than in compliant patients (p = .004) and greater in those discontinuing because of nasal symptoms than in patients who quit for other reasons (p = .05). There was a positive correlation between neutrophil counts and nasal bacterial scores, both before and after treatment with nasal CPAP.. Patients with increased neutrophil counts in the nasal scrape before beginning nasal CPAP are at increased risk of discontinuing therapy. They appear to have subclinical nasal inflammation that cannot be identified from clinical assessment, nasal symptom scores or rhinomanometry.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Continuous Positive Airway Pressure; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-13; Interleukin-6; Interleukin-8; Male; Middle Aged; Nasal Cavity; Neutrophils; Predictive Value of Tests; Rhinitis; Rhinomanometry; Sleep Apnea, Obstructive; Treatment Refusal

Obstructive sleep apnea syndrome (OSAS) is one of the most important risk factors of cardiovascular disorders. In the treatment of OSAS, nasal continuous positive airway pressure (nCPAP) has been widely used and found to be effective. In the present study, we hypothesized that the hypoxic stress caused by obstructive sleep apnea would increase circulating intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) in untreated OSAS patients compared with an age-matched control group. In addition, we hypothesized that nCPAP may decrease OSAS-induced hypoxic stress and mediators. To examine these hypotheses, we measured circulating ICAM-1 and IL-8 before and after nCPAP therapy in OSAS patients. We observed that nCPAP decreased apnea, desaturation, and the circulating ICAM-1 and IL-8 levels in OSAS patients. The circulating levels of ICAM-1, IL-8, and MCP-1 in untreated OSAS patients were significantly greater than those in the controls. These observations suggest that nCPAP therapy could reduce OSAS-induced hypoxia and generation of inflammatory mediators. Treatment of OSAS using nCPAP can be, therefore, a potential approach to decrease risk of the progression of OSAS-associated disorders.

Topics: Chemokine CCL2; Humans; Hypoxia; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Middle Aged; Positive-Pressure Respiration; Sleep Apnea, Obstructive; Stress, Physiological