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Increased Level of Interleukin 6 Associates With Increased 90-Day and 1-Year Mortality in Patients With End-Stage Liver Disease.
Remmler, J, Schneider, C, Treuner-Kaueroff, T, Bartels, M, Seehofer, D, Scholz, M, Berg, T, Kaiser, T
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018;(5):730-737
Abstract
BACKGROUND & AIMS Organ allocation for liver transplantation is based on prognosis, using the model for end-stage liver disease (MELD) or MELD including serum sodium (MELD-Na) score. These scores do not consider systemic inflammation and septic complications. Blood level of C-reactive protein (CRP), in addition to the MELD score, associates with mortality in patients with end-stage liver disease, whereas levels of interleukin 6 (IL6) have not been systematically studied. METHODS We performed a retrospective observational cohort study of 474 patients with end-stage liver disease (63.5% male; median age, 56.9 years), evaluated for liver transplantation in Germany, with at least 1 year of follow up. Data were collected on blood levels of CRP, IL6, and white blood cell count (WBC). Findings were analyzed in relation to mortality and compared with patients' MELD scores and MELD-Na scores. For survival analysis, the cohort was divided into quartiles of IL6, CRP, and WBC levels, as well as MELD scores. Log-rank test and the Cox proportional hazards regression model were used to compare the groups, and area under the receiver operating characteristic (AUROC) values were calculated. RESULTS Blood levels of IL6 and MELD scores associated with mortality: none of the patients with levels of IL6 below the first quartile (below 5.3 pg/mL) died within 1 year. In contrast, 67.7% of the patients in the highest quartile of IL6 level (37.0 pg/mL or more) died within 1 year. MELD score also correlated with mortality: among patients with MELD scores below 8.7, 0.9% died within 1 year, whereas in patients with MELD scores of 18.0 or more, 67.4% died within 1 year. The predictive value of level of IL6 (AUROC, 0.940) was higher than level of CRP (AUROC, 0.866) (P = .009) or WBC (AUROC, 0.773) (P < .001) for 90-day mortality. MELD scores associated with 90-day mortality (AUROC, 0.933) (P = .756) as did MELD-Na score (AUROC, 0.946) (P = .771). Level of IL6 associated with 1-year mortality (AUROC, 0.916) to a greater extent than liver synthesis or detoxification markers international normalized ratio (AUROC, 0.839) (P = .007) or bilirubin (AUROC 0.846) (P = .007). Level of IL6 was an independent, significant risk factor for mortality after adjustment for MELD score, MELD-Na score, level of CRP, or WBC. CONCLUSIONS In a retrospective analysis, we found high blood levels of IL6 to associate with 90-day and 1-year mortality in patients with end-stage liver disease; its predictive value was comparable to that of MELD or MELD-Na score, and was higher than that of level of CRP or WBC. Further studies should be performed to confirm the results in different cohorts.
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Circulating Interleukin-6 is a biomarker for coronary atherosclerosis in nonalcoholic fatty liver disease: Results from the Multi-Ethnic Study of Atherosclerosis.
Simon, TG, Trejo, MEP, McClelland, R, Bradley, R, Blaha, MJ, Zeb, I, Corey, KE, Budoff, MJ, Chung, RT
International journal of cardiology. 2018;:198-204
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Abstract
BACKGROUND Biomarkers to predict the presence and severity of subclinical cardiovascular disease (CVD) in nonalcoholic fatty liver disease (NAFLD) are lacking. METHODS 3876 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), without known chronic liver disease underwent baseline non-contrast cardiac CT, with NAFLD defined by validated liver:spleen ratio (L:S) < 1.0, and subclinical CVD defined by coronary artery calcium (CAC) score > 0. Randomly-selected subgroups underwent detailed inflammatory marker testing, including LpPLA2 mass (N = 2951), activity (N = 3020), high-sensitivity C-reactive protein (hsCRP; N = 3849), and interleukin-6 (IL-6; N = 3764). Among those with NAFLD, we estimated the prevalence of CAC > 0 and CAC > 100 for each SD biomarker increase, using multivariable log-binomial regression models adjusted for cardiometabolic risk factors. RESULTS Seventeen percent (N = 668) of participants met the criteria for NAFLD. NAFLD participants were younger (mean age 61 ± 10 vs. 63 ± 10 years, p < .0001) but more likely to have an elevated BMI (mean 31.1 ± 5.5 vs. 28.0 ± 5.2 kg/m2, p < .0001), diabetes (22% vs. 11%, p < .0001), and increased inflammatory biomarkers, including LpPLA2 activity, hsCRP and IL-6 (all p < .0001). Among NAFLD participants, IL-6 was the only biomarker independently associated with prevalent CAC > 0 (PR = 1.06 [1.00-1.11]), or CAC > 100 (PR = 1.09 [1.02-1.17]). In contrast, circulating LpPLA2 mass/activity and hsCRP were not associated with either the prevalence or severity of subclinical CVD (all p > .05). CONCLUSION In a large, multi-ethnic population with NAFLD, IL-6 is independently associated with the prevalence and severity of subclinical atherosclerosis. Further research into the longitudinal effects of NAFLD on progressive CVD will determine whether IL-6 is a marker or mediator of NAFLD-related atherosclerosis.
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Serum concentrations of interleukin 18 and 25-hydroxyvitamin D3 correlate with depression severity in men with psoriasis.
Pietrzak, D, Pietrzak, A, Grywalska, E, Kiciński, P, Roliński, J, Donica, H, Franciszkiewicz-Pietrzak, K, Borzęcki, A, Socha, M, Niedziałek, J, et al
PloS one. 2018;(8):e0201589
Abstract
OBJECTIVE Psoriasis and depression may have common mechanisms, such as systemic inflammation, dysfunction of the hypothalamic-pituitary-adrenal axis, and vitamin D3 deficiency. Among men with psoriasis, this study examined whether depression severity was associated with serum concentrations of different metabolic and inflammatory markers. METHODS The study included 85 men with psoriasis (mean age ± standard deviation [SD], 47 ± 14 years) and 65 men without psoriasis (mean age ± SD, 44 ± 13 years). In both groups, we measured the body mass index; blood pressure; and serum concentrations of lipids, uric acid, lipase, interleukins 6 and 18, cortisol, and 25-hydroxyvitamin D3. All participants completed the Beck Depression Inventory. Other variables analyzed included psoriasis duration, the Psoriasis Area Severity Index, and the percentage of body surface area affected by psoriatic lesions. RESULTS Compared with controls, patients with psoriasis had significantly greater depression severity, higher body mass indices, and higher serum concentrations of total cholesterol and interleukins 6 and 18; moreover, they had significantly lower serum 25-hydroxyvitamin D3 concentrations. In patients with psoriasis, depression severity correlated positively with psoriasis duration, the Psoriasis Area Severity Index, the percentage of body surface area affected by psoriatic lesions, and interleukin-18 concentration. In patients with psoriasis, depression severity correlated negatively with 25-hydroxyvitamin D3 concentration, but it did not correlate significantly with the serum concentrations of interleukin 6 and cortisol. CONCLUSIONS High concentrations of interleukin 18 and low concentrations of 25-hydroxyvitamin D3 may be associated with depression severity in men with psoriasis. Thus, further studies should examine whether effective anti-inflammatory treatments or vitamin D3 supplementation can improve depression outcomes in these patients.
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The role of IL-6 in exercise-induced anorexia in normal-weight boys.
Hunschede, S, Schwartz, A, Kubant, R, Thomas, SG, Anderson, GH
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2018;(10):979-987
Abstract
Our previous study showed that interleukin-6 (IL-6) is associated with suppression of appetite after high-intensity exercise (HIEX), but an independent role in food intake (FI) was not defined. We hypothesized that IL-6 suppresses appetite and FI, independently of appetite hormones, after HIEX in normal-weight (NW) boys. We investigated the effect of HIEX, with and without the inflammation inhibitor ibuprofen (IBU), on IL-6, other biomarkers of inflammation and appetite, FI, and ratings of appetite in NW boys. Fifteen NW boys (aged 13-18 years) were randomly assigned in a crossover design to 4 sessions: (i) water and rest, (ii) IBU and rest, (iii) water and HIEX, and (iv) IBU and HIEX. HIEX consisted of three 10-min bouts of exercise at 75% of maximal oxygen uptake with 90 s of active rest between bouts. IBU (300 mg) was given as a liquid suspension. FI, ratings of appetite, and plasma biomarkers of appetite, inflammation, stress, and glucose control were measured. FI was not affected by HIEX or IBU. Appetite increased over time (p = 0.002) but was lower after HIEX (p < 0.001) and not affected by IBU. HIEX, but not IBU, resulted in higher levels of IL-6 (p < 0.001) and cortisol (p < 0.001) and lower active ghrelin (p < 0.001). IL-6 correlated with active ghrelin (r = 0.37; p = 0.036) and cortisol (r = 0.26; p = 0.049). An independent role for IL-6 in appetite suppression was not supported. However, IL-6 was correlated with active ghrelin and cortisol, thus potentially mediating appetite via these interactions.
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Aerobic Exercise Training and Inducible Inflammation: Results of a Randomized Controlled Trial in Healthy, Young Adults.
Sloan, RP, Shapiro, PA, McKinley, PS, Bartels, M, Shimbo, D, Lauriola, V, Karmally, W, Pavlicova, M, Choi, CJ, Choo, TH, et al
Journal of the American Heart Association. 2018;(17):e010201
Abstract
Background Consensus panels regularly recommend aerobic exercise for its health-promoting properties, due in part to presumed anti-inflammatory effects, but many studies show no such effect, possibly related to study differences in participants, interventions, inflammatory markers, and statistical approaches. This variability makes an unequivocal determination of the anti-inflammatory effects of aerobic training elusive. Methods and Results We conducted a randomized controlled trial of 12 weeks of aerobic exercise training or a wait list control condition followed by 4 weeks of sedentary deconditioning on lipopolysaccharide (0, 0.1, and 1.0 ng/mL)-inducible tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and on toll-like receptor 4 in 119 healthy, sedentary young adults. Aerobic capacity by cardiopulmonary exercise testing was measured at study entry (T1) and after training (T2) and deconditioning (T3). Despite a 15% increase in maximal oxygen consumption, there were no changes in inflammatory markers. Additional analyses revealed a differential longitudinal aerobic exercise training effect by lipopolysaccharide level in inducible TNF -α ( P=0.08) and IL-6 ( P=0.011), showing T1 to T2 increases rather than decreases in inducible (lipopolysaccharide 0.1, 1.0 versus 0.0 ng/mL) TNF- α (51% increase, P=0.041) and IL-6 (42% increase, P=0.11), and significant T2 to T3 decreases in inducible TNF- α (54% decrease, P=0.007) and IL-6 (55% decrease, P<0.001). There were no significant changes in either group at the 0.0 ng/mL lipopolysaccharide level for TNF- α or IL-6. Conclusions The failure to support the primary hypotheses and the unexpected post hoc findings of an exercise-training-induced proinflammatory response raise questions about whether and under what conditions exercise training has anti-inflammatory effects. Clinical Trial Registration URL http://www.clinicaltrials.gov . Unique identifier: NCT 01335737.
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Improvement in dietary inflammatory index score after 6-month dietary intervention is associated with reduction in interleukin-6 in patients with coronary heart disease: The AUSMED heart trial.
Mayr, HL, Itsiopoulos, C, Tierney, AC, Ruiz-Canela, M, Hebert, JR, Shivappa, N, Thomas, CJ
Nutrition research (New York, N.Y.). 2018;:108-121
Abstract
The Dietary Inflammatory Index (DII) was designed to measure the inflammatory potential of one's diet. Evidence from observational studies supports that a higher (ie, more pro-inflammatory) DII score is associated with inflammation and cardiometabolic diseases. We hypothesized that reduction in DII score would improve inflammatory cytokines. To test this hypothesis, we assessed data from a dietary intervention trial in patients with diagnosed coronary heart disease (CHD) to determine whether reduction in DII scores through healthy diets is linked to improvement in inflammatory and related cardiometabolic risk markers. Participants (n = 65, 83% male) were randomized to a Mediterranean diet or low-fat diet intervention for 6-months. Anthropometry, body composition and blood markers were measured and DII scores were calculated from 7-day food diaries. After 6-months, in participants who completed the intervention (n = 56), reduction in DII score correlated significantly with reduction in high sensitivity interleukin-6 (hs-IL-6) (r = 0.34, 95% CI 0.05, 0.56) and triglycerides (r = -0.30, 95% CI -0.51, -0.06) but not with C-reactive protein, adiponectin, glucose, body composition or anthropometry. The adjusted mean difference in hs-IL-6 and triglycerides between the highest and lowest tertiles of DII improvement was -0.47 pg/mL (95% CI 0.41, 1.10) and +0.30 mmol/L (95% CI 1.06, 1.59), respectively. The present study found that improvement in DII score through healthy diet intervention was linked with reduced levels of hs-IL-6, but also increased triglycerides, in adult Australian patients with CHD. Future research is warranted to investigate the impact of change in DII on cardiometabolic risk markers in larger cohorts, other disease populations or healthy subjects and with longer-term follow up.
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Could the biomarker levels in saliva help distinguish between healthy implants and implants with peri-implant disease? A systematic review.
Gomes, AM, Douglas-de-Oliveira, DW, Oliveira Costa, F
Archives of oral biology. 2018;:216-222
Abstract
BACKGROUND The most accurate data help to minimize possible mistakes on a patient´s evaluation, as more robust findings are necessary to establish a correct diagnosis, prognosis and, consequently, better treatment. PURPOSE Could biomarker levels in the saliva help to distinguish between healthy implants and implants with peri-implant disease? MATERIALS AND METHODS An electronic database search of Pubmed/MEDLINE, Web of Science, the Cochrane Library, OVID and Scielo was performed. The articles and abstracts identified were considered relevant if they compared cytokine levels in saliva from patients with healthy implants to those in saliva from patients with untreated peri-implantitis. RESULTS Lower salivary levels of interleukin 1β were found in healthy implants than in inflamed implants. A significantly positive correlation was found between the salivary levels of IL-6 and peri-implant inflammatory conditions. The salivary concentrations of total antioxidants, urate and ascorbate were higher in healthy implants than in inflamed implants. The data extracted from the 6 studies evaluated in this review revealed heterogeneity in relation to the clinical parameters assessed, implant restoration, bone loss and peri-implant disease definitions. CONCLUSIONS There was no clear, developed basis for using any specific biomarker in a clinical setting to distinguish between healthy implants and those with peri implant disease.
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Randomization to 6-month Mediterranean diet compared with a low-fat diet leads to improvement in Dietary Inflammatory Index scores in patients with coronary heart disease: the AUSMED Heart Trial.
Mayr, HL, Thomas, CJ, Tierney, AC, Kucianski, T, George, ES, Ruiz-Canela, M, Hebert, JR, Shivappa, N, Itsiopoulos, C
Nutrition research (New York, N.Y.). 2018;:94-107
Abstract
A higher dietary inflammatory index (DII®) score is associated with inflammation and incidence of coronary heart disease (CHD). We hypothesized that a Mediterranean diet (MedDiet) intervention would reduce DII score. We assessed dietary data from a randomized controlled trial comparing 6-month MedDiet versus low-fat diet intervention, in patients with CHD. We aimed to determine the DII scores of the prescribed diets' model meal plans, followed by whether dietary intervention led to lower (i.e., more anti-inflammatory) DII scores and consequently lower high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (hs-IL-6). DII scores were calculated from 7-day food diaries. The MedDiet meal plan had a markedly lower DII score than the low-fat diet meal plan (-4.55 vs. -0.33, respectively). In 56 participants who completed the trial (84% male, mean age 62 ± 9 years), the MedDiet group significantly reduced DII scores at 6 months (n = 27; -0.40 ± 3.14 to -1.74 ± 2.81, P = .008) and the low-fat diet group did not change (n = 29; -0.17 ± 2.27 to 0.05 ± 1.89, P = .65). There was a significant post-intervention adjusted difference in DII score between groups (compared to low-fat, MedDiet decreased by -1.69 DII points; P = .004). When compared to the low-fat diet, the MedDiet non-significantly reduced hs-IL-6 (-0.32 pg/mL, P = .29) and increased hs-CRP (+0.09 mg/L, P = .84). These findings demonstrated that MedDiet intervention significantly reduced DII scores compared to a low-fat diet. However, in this small cohort of patients with CHD this did not translate to a significant improvement in measured inflammatory markers. The effect of improvement in DII with MedDiet should be tested in larger intervention trials and observational cohorts.
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Which cytokine is the most related to weight loss-induced decrease in arterial stiffness in overweight and obese men?
Kumagai, H, Zempo-Miyaki, A, Yoshikawa, T, Eto, M, So, R, Tsujimoto, T, Nishiyasu, T, Tanaka, K, Maeda, S
Endocrine journal. 2018;(1):53-61
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Abstract
Obesity and increased arterial stiffness are risk factors for cardiovascular disease. A well-known characteristic of obesity is the chronic low-grade inflammatory state, and it causes elevation of arterial stiffness. Weight-loss reduces arterial stiffness and inflammatory level in obese individuals. However, it is unclear which inflammatory factor is most related to weight loss-induce decreases in arterial stiffness in overweight and obese men. Thus, the aim of this study was to determine which circulating cytokine level has the most effect on decreasing arterial stiffness after lifestyle modification. Twenty overweight and obese men completed a 12-week period of lifestyle modifications (combination of aerobic exercise training and dietary modification). We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness, and circulating cytokine levels using comprehensive analysis. After the 12-week lifestyle modifications, body mass was markedly decreased. Also, baPWV and the levels of several circulating cytokines significantly decreased after the lifestyle modifications. We observed a positive correlation between changes in baPWV and circulating interleukin-6 (IL-6) levels. Furthermore, multiple liner regression analysis revealed that change in baPWV was significantly associated with that in IL-6 levels after consideration of changes in systolic blood pressure and body mass index. These results suggest that for overweight and obese men, a 12-week period of lifestyle modifications-induced a decrease in circulating cytokine levels (especially IL-6 levels), leads to decreased baPWV.
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The study of vitamin D administration effect on CRP and Interleukin-6 as prognostic biomarkers of ventilator associated pneumonia.
Miroliaee, AE, Salamzadeh, J, Shokouhi, S, Sahraei, Z
Journal of critical care. 2018;:300-305
Abstract
PURPOSE In regard with the effect of immune-stimulants in the treatment of infectious diseases, the effect of vitamin D administration on the outcome of patients with Ventilator-Associated Pneumonia (VAP) with a high rate of mortality, was studied. MATERIAL AND METHOD In this trial, 46 adult patients suffering from VAP and vitamin D deficiency were enrolled. The first group of patients received single intramuscular injection of vitamin D (300000Unit), while the other group were given the placebo. RESULTS Administration of vitamin D significantly enhanced its levels (P<0.0001) in the treated patients (12.28±8.26) in comparison with placebo group (1.15±1.50). Serum Interleukin-6 levels were significantly reduced in the treated group compared to placebo (P=0.01). Although C-Reactive protein (CRP) levels showed an improving trend in the vitamin D group, no significant difference between groups (P=0.12) was found. Interestingly, the mortality rate of patients that treated with vitamin D (5/24) was significantly lower (p=0.04) than that of the placebo group (11/22). CONCLUSION Our results indicate that vitamin D administration can significantly reduce the IL-6 as prognostic marker in VAP patients, and must be considered as adjunct option in the treatment of VAP patients.