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A prospective observational study of urinary cytokines and inflammatory response in patients with Overactive Bladder Syndrome.
Gill, K, Horsley, H, Swamy, S, Khasriya, R, Malone-Lee, J
BMC urology. 2021;(1):39
Abstract
BACKGROUND Contemporary studies have discredited the methods used to exclude urinary tract infection (UTI) when treating overactive bladder (OAB). Thus we must revisit the OAB phenotype to check that UTI has not been overlooked. AIMS To examine the differences in urinary cytokines IL6 and lactoferrin in OAB patients compared to controls, with references to microscopy of urine and enhanced quantitative urine culture. METHODS A blinded, prospective cohort study with normal controls using six repeated measures, achieved two-monthly, over 12 months. RESULTS The differences between patients and controls in urine IL6 (F = 49.0, p < .001) and lactoferrin (F = 228.5, p < .001) were significant and of a magnitude to have clinical implications. These differences were for lactoferrin correlated to symptoms (9.3, p = .003); for both to pyuria (IL6 F = 66.2, p < .001, Lactoferrin F = 73.9, p < .001); and for IL6 microbial abundance (F = 5.1, p = .024). The pathological markers had been missed by urinary dipsticks and routine MSU culture. CONCLUSION The OAB phenotype may encompass patients with UTI that is being overlooked because of the failure of standard screening methods.
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Poor Masticatory Capacity and Blood Biomarkers of Elevated Cardiovascular Disease Risk in the Community: The Paris Prospective Study III.
Chatzopoulou, E, Rangé, H, Deraz, O, Boutouyrie, P, Perier, MC, Guibout, C, Thomas, F, Andrieu, M, Bailly, K, Vedie, B, et al
Arteriosclerosis, thrombosis, and vascular biology. 2021;(7):2225-2232
Abstract
[Figure: see text].
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Effects of GLP-1 receptor agonists on myokine levels and pro-inflammatory cytokines in patients with type 2 diabetes mellitus.
Guarnotta, V, Bianco, MJ, Vigneri, E, Panto', F, Lo Sasso, B, Ciaccio, M, Pizzolanti, G, Giordano, C
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(11):3193-3201
Abstract
BACKGROUND AND AIMS To evaluate the change in circulating serum irisin and interleukin-6 (IL-6), in patients with type 2 diabetes mellitus (T2DM) after 6 and 12 months of GLP-1 treatment. METHODS AND RESULTS Eighty-five patients with T2DM inadequately controlled with insulin or other hypoglycaemic drugs were added to dulaglutide (N° = 44) and liraglutide (N° = 41) treatment. After 6 months of GLP-1 analogues a significant decrease in BMI (p < 0.001), waist circumference (WC) (p < 0.001), fasting blood glucose (p < 0.001), HbA1c (p < 0.001), total cholesterol (p < 0.001), LDL-cholesterol (p = 0.003), triglycerides (p = 0.017), IL-6 (p = 0.045) and a significant increase in serum irisin (p < 0.001) were observed compared to baseline. After 12 months of treatment no significant differences were found compared to the levels at 6 months. The change in irisin from baseline (Δ_irisin) was significantly related to the changes in total-cholesterol (Δ_total-cholesterol) (r = -0.293; p = 0.020), while the change in IL-6 (Δ_IL-6) was significantly related to the changes in WC (Δ_WC) (r = 0.347; p = 0.006). CONCLUSIONS Additive treatment with GLP1-analogues results in an increase in serum circulating irisin levels and a decrease in IL-6. The post-treatment change in irisin was correlated with a decrease in total cholesterol, while the change in IL-6 was correlated with a decrease in WC.
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Interaction Between Vitamin D and Interleukin 6 on Slow Gait Speed: 6-Year Follow-up Data of Older Adults From InCHIANTI.
Kositsawat, J, Kuo, CL, Barry, LC, Melzer, D, Bandinelli, S, Ferrucci, L, Wu, R, Kuchel, GA
The journals of gerontology. Series A, Biological sciences and medical sciences. 2020;(6):1161-1166
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BACKGROUND Whereas the independent effects of biomarkers, including 25-hydroxy vitamin D (25(OH)D), insulin-like growth factor 1, C-reactive protein, and interleukin 6 (IL-6), on gait speed in older adults have been evaluated, their joint effects on gait speed are not well understood. METHODS Study subjects aged at least 65 at baseline (N = 970) were enrolled in the population-based Invecchiare in Chianti (InCHIANTI) study from 1998 to 2000 and were followed up at 3 and 6 years. All above biomarkers and gait speed data were measured at each of the three time points. Using a generalized estimating equation approach, we determined if slow gait speed (<0.8 m/s) was associated with the biomarkers. Further investigation was conducted for interactions between high IL-6 (≥.87 pg/mL) and other biomarkers focusing on low 25(OH)D (<20 ng/mL). RESULTS After controlling for other biomarkers and potential confounders, IL-6 emerged as the only biomarker independently associated with gait speed. The association between high IL-6 and slow gait speed was enhanced by low 25(OH)D, with significant interaction between high IL-6 and low 25(OH)D (p = .038). The odds ratio of slow gait speed for low 25(OH)D and high IL-6 was 1.63 (95% confidence interval [CI]: 1.15, 2.32) compared with the reference groups with both biomarker levels at the other ends. CONCLUSION The association of low vitamin D with slow gait speed statistically interacts with high IL-6. Coexisting vitamin D insufficiency and inflammation may provide a better biomarker for identifying those at risk of developing impairments in gait speed than either factor alone.
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Efficacy of autologous bone marrow mesenchymal stem cells in the treatment of knee osteoarthritis and their effects on the expression of serum TNF-α and IL-6.
Li, J, Shao, Q, Zhu, X, Sun, G
Journal of musculoskeletal & neuronal interactions. 2020;(1):128-135
Abstract
OBJECTIVE To investigate the clinical efficacy of autologous bone marrow mesenchymal stem cell (BMSC) transplantation in the treatment of knee osteoarthritis (OA) and its effect on the expression of serum TNF-α and IL-6. METHODS The clinical data of 86 patients with knee OA treated in the Shanghai East Hospital Tongji University from March 2015 to March 2017 were analyzed retrospectively. Observation group (treated with intraarticular injection of autologous BMSC); Control group (treated with arthroscopic debridement and injected with sodium hyaluronate). The patients were followed up for 1 year after treatment, the clinical efficacy was evaluated by the Lysholm Knee Scale (Lysholm), Visual analog scale (VAS), and the expression of serum TNF-α and IL-6 was detected by ELISA. RESULTS The expression of TNF-α and IL-6 at 6 and 12 months after surgery was significantly lower than that before surgery (P<0.05). CONCLUSIONS The Lysholm score and total effective rate of knee OA patients underwent BMSC transplantation are better than that of joint debridement, while the VAS score was lower than that of joint debridement. Meanwhile, BMSC transplantation seems to reduce the postoperative inflammatory reaction.
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The clinical significance of interleukin-6 in heart failure: results from the BIOSTAT-CHF study.
Markousis-Mavrogenis, G, Tromp, J, Ouwerkerk, W, Devalaraja, M, Anker, SD, Cleland, JG, Dickstein, K, Filippatos, GS, van der Harst, P, Lang, CC, et al
European journal of heart failure. 2019;(8):965-973
Abstract
AIMS: Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)-α were largely unsuccessful. Interleukin (IL)-6 is an important inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL-6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations. METHODS AND RESULTS Interleukin-6 was measured in 2329 patients [89.4% with a left ventricular ejection fraction (LVEF) ≤ 40%] of the BIOSTAT-CHF cohort. The primary outcome was all-cause mortality and HF hospitalization during 2 years, with all-cause, cardiovascular (CV), and non-CV death as secondary outcomes. Approximately half (56%) of all included patients had plasma IL-6 values greater than the previously determined 95th percentile of normal values at baseline. Elevated N-terminal pro-brain natriuretic peptide, procalcitonin and hepcidin, younger age, TNF-α/IL-1-related biomarkers, or having iron deficiency, atrial fibrillation and LVEF > 40% independently predicted elevated IL-6 levels. IL-6 independently predicted the primary outcome [HR (95% confidence interval) per doubling: 1.16 (1.11-1.21), P < 0.001], all-cause mortality [1.22 (1.16-1.29), P < 0.001] and CV as well as non-CV mortality [1.16 (1.09-1.24), P < 0.001; 1.31 (1.18-1.45), P < 0.001], but did not improve discrimination in previously published risk models. CONCLUSIONS In a large, heterogeneous cohort of HF patients, elevated IL-6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL-6 as a potential therapeutic target in specific HF subpopulations.
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Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation.
Jevnikar, Z, Östling, J, Ax, E, Calvén, J, Thörn, K, Israelsson, E, Öberg, L, Singhania, A, Lau, LCK, Wilson, SJ, et al
The Journal of allergy and clinical immunology. 2019;(2):577-590
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BACKGROUND Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. OBJECTIVE We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. METHODS An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. RESULTS Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1β, IL-8, and IL-1β. CONCLUSIONS Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.
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Bariatric surgery as a model to explore the basis and consequences of the Reaven hypothesis: Small, dense low-density lipoprotein and interleukin-6.
Adam, S, Liu, Y, Siahmansur, T, Ho, JH, Dhage, SS, Yadav, R, New, JP, Donn, R, Ammori, BJ, Syed, AA, et al
Diabetes & vascular disease research. 2019;(2):144-152
Abstract
BACKGROUND Reaven originally described the clustering of insulin resistance/hyperinsulinaemia, obesity (particularly visceral), altered cytokine levels, glucose intolerance, hypertriglyceridaemia and low high-density lipoprotein cholesterol. Subsequently, a potentially highly atherogenic small, dense low-density lipoprotein was also reported. We have studied the effect of bariatric surgery on this and other risk factors for atherosclerosis. METHODS Forty patients (20 with type 2 diabetes mellitus) undergoing bariatric surgery were studied before and 1 year after bariatric surgery. RESULTS Twelve months after bariatric surgery, median body mass index had decreased from 49.5 to 36.5 kg/m2, fasting insulin from 21.3 to 7.8 mU/L and insulin resistance (homeostatic model assessment of insulin resistance) from 5.9 to 1.8 (all p < 0.001). Thirteen out of 20 patients had remission from type 2 diabetes mellitus. Highly sensitive C-reactive protein, interleukin-6, fasting triglycerides ( p < 0.001) and small, dense low-density lipoprotein ( p < 0.001) decreased, while high-density lipoprotein cholesterol increased ( p < 0.001) significantly, irrespective of having type 2 diabetes mellitus and/or being treated with statin therapy before surgery. CONCLUSION The association between marked weight loss and change in insulin resistance and hyperinsulinaemia with the change in small, dense low-density lipoprotein and interleukin-6 warrants further investigation. Bariatric surgery provides a model for investigating the mechanisms linking insulin resistance/hyperinsulinaemia to atherosclerosis.
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Screening for frailty among older patients with cancer using blood biomarkers of inflammation.
Harneshaug, M, Kirkhus, L, Benth, JŠ, Grønberg, BH, Bergh, S, Whist, JE, Rostoft, S, Jordhøy, MS
Journal of geriatric oncology. 2019;(2):272-278
Abstract
INTRODUCTION As frailty is associated with inflammation, biomarkers of inflammation may represent objective measures that could facilitate the identification of frailty. Glasgow prognostic score (GPS), combines C-reactive protein (CRP) and albumin, and is scored from 0 to 2 points. Higher score indicates a higher degree of inflammation. OBJECTIVES To investigate whether (1) GPS is associated with frailty, (2) GPS could be used to screen for frailty, (3) IL-6 and TNF-α add to the accuracy of GPS as a screening tool, and (4) GPS adds prognostic information in frail older patients with cancer. METHODS Prospective, observational study of 255 patients ≥70 years with solid malignant tumours referred for medical cancer treatment. At baseline, frail patients were identified by a modified Geriatric Assessment (mGA), and blood samples were collected. RESULTS Mean age was 76.7 years, 49.8% were frail, and 56.1% had distant metastases. The proportion of frail patients increased with higher GPS (GPS zero: 43.2%, GPS one: 52.7%, GPS two: 94.7%). GPS two was significantly associated with frailty (OR 18.5), independent of cancer type, stage, BMI and the use of anti-inflammatory drugs. The specificity of GPS was high (99%), but the sensitivity was low (14%). Frail patients with GPS two had poorer survival than patients with GPS zero-one. TNF-α and IL-6 did not improve the accuracy of GPS when screening for frailty. CONCLUSION Frailty and GPS two are strongly associated, and GPS two is a significant prognostic factor in frail, older patients with cancer. The inflammatory biomarkers investigated are not suitable screening tools for frailty.
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Impact of angiotension I converting enzyme gene I/D polymorphism on running performance, lipid, and biochemical parameters in ultra-marathoners.
Chiu, YH, Lai, JI, Tseng, CY, Wang, SH, Li, LH, Kao, WF, How, CK, Chang, WH, Hsieh, CY
Medicine. 2019;(29):e16476
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Abstract
The insertion (I) or deletion (D) polymorphism in the angiotension I converting enzyme gene, (ACE I/D, rs1799752) is associated with human exercise endurance and performance. However, most of the aforementioned studies focus on marathons, swimming, and triathlons, while the ACE polymorphism in ultra-marathoners has not yet been reported. We studied the impact of ACE I/D polymorphism in ultra-marathoners and investigated its relationship with lipid profiles, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) levels in runners before and after ultra-marathon racing.This observational study used data from a 100-km ultra-marathon in Taipei, Taiwan. Twenty-four male participants were analyzed for their ACE insertion/deletion polymorphism, lipid profiles, hs-CRP, IL-6 in serum immediately before and after ultra-marathon running.In our 24 subjects analyzed, 7, 14, and 3 subjects were of I/I, I/D, and D/D genotypes, respectively. Runners with the D polymorphism (I/D and D/D) showed a trend of better performance in the 100-km ultra-marathon (measured by completion time in minutes, P = .036). In this group, the previous best marathon performance was also significantly better than the I/I group (P = .047). After adjusting for body mass index (BMI), the difference in performance was not significant. Ketone levels, IL-6, and hs-CRP levels were highly increased at immediately and 24-hour post-race. No correlation was found between different ACE polymorphisms and common biochemical parameters examined.We report the first study in the impact of the ACE I/D (rs1799752) on ultra-marathoners. Presence of the D polymorphism in ACE gene is associated with better performance, although the BMI of the runners contribute as a major factor. There was no difference in the biochemical or lipid parameters measured among different ACE polymorphisms.