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Cytokine-specific autoantibodies shape the gut microbiome in autoimmune polyendocrine syndrome type 1.
Petersen, AØ, Jokinen, M, Plichta, DR, Liebisch, G, Gronwald, W, Dettmer, K, Oefner, PJ, Vlamakis, H, Chung, DC, Ranki, A, et al
The Journal of allergy and clinical immunology. 2021;(3):876-888
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Abstract
BACKGROUND Gastrointestinal dysfunction is a frequent and disabling manifestation of autoimmune polyendocrine syndrome type 1 (APS-1), a rare monogenic multiorgan autoimmune disease caused by the loss of central AIRE-controlled immune tolerance. OBJECTIVES This study aimed to understand the role of the gut microbiome in APS-1 symptoms and potentially alleviate common gastrointestinal symptoms by probiotic intervention. METHODS This study characterized the fecal microbiomes of 28 patients with APS-1 and searched for associations with gastrointestinal symptoms, circulating anti-cytokine autoantibodies, and tryptophan-related metabolites. Additionally, daily doses of the probiotic Lactobacillus rhamnosus GG were administered for 3 months. RESULTS Of 581 metagenomic operational taxonomic units (mOTUs) characterized in total, 14 were significantly associated with patients with APS-1 compared with healthy controls, with 6 mOTUs depleted and 8 enriched in patients with APS-1. Four overabundant mOTUs were significantly associated with severity of constipation. Phylogenetically conserved microbial associations with autoantibodies against cytokines were observed. After the 3-month intervention with the probiotic L rhamnosus GG, a subset of gastrointestinal symptoms were alleviated. L rhamnosus GG abundance was increased postintervention and corresponded with decreased abundances of Alistipes onderdonkii and Collinsella aerofaciens, 2 species positively associated with severity of diarrhea in patients with APS-1. CONCLUSIONS The APS-1 microbiome correlates with several APS-1 symptoms, some of which are alleviated after a 3-month L rhamnosus GG intervention. Autoantibodies against cytokines appear to shape the gut microbiome by positively correlating with a taxonomically consistent group of bacteria.
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Effect of mate tea (Ilex paraguariensis) on the expression of the leukocyte NADPH oxidase subunit p47phox and on circulating inflammatory cytokines in healthy men: a pilot study.
Panza, VP, Brunetta, HS, de Oliveira, MV, Nunes, EA, da Silva, EL
International journal of food sciences and nutrition. 2019;(2):212-221
Abstract
Increased superoxide production by phagocytic NADPH oxidase has been associated with inflammatory conditions. Growing evidences suggest that dietary polyphenols may modulate the expression of NADPH oxidase subunits. Herein, we examined whether soluble mate tea (SMT) consumption - a polyphenol-rich beverage - affects the expression of the leukocyte NADPH oxidase protein p47phox and/or circulating biomarkers of inflammation and antioxidant biomarkers in humans. In a two-phase study, nine men were requested to drink water (control) for 8 d and then follow a second 8-d period drinking SMT. Blood samples were analysed for p47phox protein in CD16+/CD14- cells, interleukin (IL)-1β (IL-1β), tumour necrosis factor-alpha (TNF-α), IL-6, total phenols, and reduced and oxidised glutathione (GSH and GSSG, respectively) after each study phase. After SMT intake, CD16+/CD14- cells' p47phox protein and serum TNF-α and IL-6 levels were significantly attenuated (P < .05) while plasma phenolic compounds and blood GSH:GSSG ratio were significantly enhanced (P < .05). Consumption of SMT favourably affected leukocytes' p47phox expression and inflammatory cytokine and antioxidants levels in peripheral blood, which may help decrease oxidative stress and low-grade inflammation.
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Metabolic Changes in Androgen-Deprived Nondiabetic Men With Prostate Cancer Are Not Mediated by Cytokines or aP2.
Gagliano-Jucá, T, Burak, MF, Pencina, KM, Li, Z, Edwards, RR, Travison, TG, Basaria, S
The Journal of clinical endocrinology and metabolism. 2018;(10):3900-3908
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Abstract
CONTEXT Androgen deprivation therapy (ADT) remains the cornerstone of management of prostate cancer (PCa). Previous studies have shown that men undergoing ADT develop insulin resistance and diabetes, but the mechanisms behind ADT-induced metabolic abnormalities remain unclear. OBJECTIVE To evaluate the role of inflammatory cytokines and adipocyte protein-2 (aP2) in ADT-induced metabolic dysfunction. PARTICIPANTS AND INTERVENTIONS This 6-month prospective cohort study enrolled nondiabetic men with PCa about to undergo ADT (ADT group) and a control group of nondiabetic men who had previously undergone prostatectomy for localized PCa and were in remission (non-ADT group); all participants had normal testosterone at study entry. Fasting blood samples were collected at baseline and at 6, 12, and 24 weeks after initiation of ADT and at the same intervals in the non-ADT group. Glucose, insulin, lipids, inflammatory cytokines, and C-reactive protein were measured. We also measured serum aP2, an adipocyte-secreted protein that promotes hepatic glucose production. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. RESULTS Seventy-three participants formed the analytical sample (33 ADT, 40 non-ADT). HOMA-IR increased in the ADT group (estimated change = 0.25; P = 0.05), but was unchanged in the non-ADT group (0.11; P = 0.342). Serum concentrations of inflammatory cytokines or aP2 did not change significantly. There was a treatment-associated increase in total (16 mg/dL; P < 0.001), high-density lipoprotein (8 mg/dL; P < 0.001), and low-density lipoprotein (7 mg/dL; P = 0.02) cholesterol. CONCLUSION ADT-induced metabolic abnormalities were not associated with changes in circulating inflammatory cytokines or aP2 levels.
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Effect of oral administration involving a probiotic strain of Lactobacillus reuteri on pro-inflammatory cytokine response in patients with chronic periodontitis.
Szkaradkiewicz, AK, Stopa, J, Karpiński, TM
Archivum immunologiae et therapiae experimentalis. 2014;(6):495-500
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Abstract
This study aimed at evaluation of pro-inflammatory cytokine response (TNF-α, IL-1β and IL-17) in patients with chronic periodontitis administered per os with a probiotic strain of Lactobacillus reuteri. In the 38 adult patients with moderate chronic periodontitis, professional cleaning of teeth was performed. Two weeks after performing the oral hygienization procedures, clinical examination permitted to distinguish a group of 24 patients (Group 1) in whom treatment with probiotic tablets containing L. reuteri strain, producing hydrogen peroxide (Prodentis), was conducted. In the remaining 14 patients, no probiotic tablet treatment was applied (the control group; Group 2). From all patients in two terms, gingival crevicular fluid (GCF) was sampled from all periodontal pockets. Estimation of TNF-α, IL-lβ and IL-17 in GCF was performed using the ELISA method. After completion of the therapy with probiotic tablets, 18 (75%) of the patients of Group 1 have manifested a significant decrease in levels of studied pro-inflammatory cytokines (TNF-α, IL-1β and IL-17). In parallel, we have detected an improvement of clinical indices [sulcus bleeding index (SBI), periodontal probing depth (PPD), clinical attachment level (CAL)]. At individuals of Group 2 levels of studies, pro-inflammatory cytokines and clinical indices (SBI, PPD, CAL) were significantly higher than in Group 1. Results obtained in this study indicate that application of oral treatment with tablets containing probiotic strain of L. reuteri induces in most patients with chronic periodontitis a significant reduction of pro-inflammatory cytokine response and improvement of clinical parameters (SBI, PPD, CAL). Therefore, such an effect may result in a reduced activity of the morbid process.
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[Correlation between concentration of pathological cytokines and erythropoietin in patients with chronic heart failure with anemic syndrome].
Zakhidova, KKh
Vestnik Rossiiskoi akademii meditsinskikh nauk. 2014;(1-2):32-7
Abstract
AIM: To study correlation between concentration of pathological cytokines and erythropoietin inpatients with chronic heart failure anemic syndrome and also to prove importance of this communication for need of appointment erythropoietin excitants. PATIENTS AND METHODS 94 patients with chronic heart failure of New York Heart Association (NYHA) class III-IV a left ventricular ejection fraction of 40% or less withanemia w ere idied in inveslain (58 males, 36 females). Anemia was detected when hemoglobin (b) was less than 120 g/l in males and less than in females. 46 patients received traditional treatment of CHF (I group) and 48 patients were treated additionally with erythropoietin (EPO) (II group). Percutaneous EPO 50 IU monthly to patients without iron deficiency for a period of 6 months. Echocardiography parameters, plasma NT and pro-BNP, cytokines, EPO, feritin and 6-minute walking test were assessed at baseline and after treatment. RESULT in patients with CHF and anemia in II group erythropoietin treatment increased Hb levels by 22.4% (p < 0.05) and erythropoietin serum levels by 29.3 +/- 14.3 IU/ml (p < 0.001). Increased erythropoietin level was associated with decrease of cytokines levels: IL 1 by 36.6% (p < 0.001), IL 6 by 54.3% (p < 0.05), TNF alpha by 48.3% (p < 0.05) compared with patients in I group. In erythropoietin-treated patients there is a significant increase of LVEF by 19.04% (p < 0.05) compared with patients from I group. A greater 6-minute distance walked on exercise testing increased by 76.6% (p < 0.05) after treatment with erythropoieitin. CONCLUSIONS Correction of anemia in patients with chronic heart failure with percutaneous erythropoietin injections 50 IU monthly for 6 month period to improve erythropoietin deficit and cytokines aggression and associated anemia, symptoms and quaity of life.
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The association of oxidative stress and pro-inflammatory cytokines in diabetic patients with hyperglycemic crisis.
Li, J, Huang, M, Shen, X
Journal of diabetes and its complications. 2014;(5):662-6
Abstract
AIMS: To investigate the relationship between oxidative stress and serum levels of pro-inflammatory cytokines in diabetic patients with hyperglycemic crisis. METHODS Seventy-three patients presenting to hospital with diabetic ketoacidosis or non-ketotic hyperglycemia were studied. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant capacity (TAC), 8-iso-prostaglandin F2α (8-iso-prostaglandinF2α, 8-iso-PGF2α), tumor necrosis factor receptor-I (TNF-RI), interleukin -1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were measured in all patients. The patients were then given an intravenous infusion of insulin 0.1U • kg-1 • h-1, as well as fluids, symptomatic therapy and parenteral and intravenous nutrition. RESULTS CONCLUSION Patients with hyperglycemic crises have significantly increased oxidative stress and dysregulated serum pro-inflammatory cytokines that can be effectively treated by intensive insulin therapy.
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Metabolic complications and selected cytokines in HIV-infected individuals.
Bociąga-Jasik, M, Polus, A, Góralska, J, Śliwa, A, Raźny, U, Zdzienicka, A, Garlicki, A, Mach, T, Dembińska-Kieć, A
Polskie Archiwum Medycyny Wewnetrznej. 2014;(1-2):27-35
Abstract
INTRODUCTION Human immunodeficiency virus (HIV)-infected individuals are at a higher risk of developing metabolic disturbances. The pathogenesis of these complications is complex and not fully explored. OBJECTIVES The aim of the study was to investigate the effect of HIV infection and antiretroviral (ARV) therapy on the development of metabolic changes and adipocytokine concentrations. The analysis of the differences in the investigated parameters among lipodystrophic and nonlipodystrophic patients was also performed. PATIENTS AND METHODS A total of 42 HIV‑infected patients on ARV therapy (HIV[+]ARV[+]), 13 HIV‑infected ARV naive patients (HIV[+]ARV[-]), and 20 healthy controls were included in the study. A lipid profile, fasting free fatty acids (FFAs), glucose, insulin, and insulin resistance (homeostasis model assessment of insulin resistance--HOMA‑IR) were tested. Serum concentrations of tumor necrosis factor α (TNF‑α), interleukin 6 (IL‑6), adiponectin, leptin, and fatty acid-binding protein 4 (FABP4) were determined. RESULTS Increased FFA levels were observed in HIV(+)ARV(-) patients. HIV(+)ARV(+) patients had significantly higher triglycerides and insulin level compared with controls. HOMA‑IR showed a tendency to be higher in HIV(+)ARV(+) patients compared with the other study groups. The ARV therapy longer than 2 years resulted in more pronounced metabolic abnormalities. HIV infection itself had a significant effect on inflammation expressed by elevated TNF‑α and IL‑6 levels. We did not observe differences in adiponectin and FABP4 concentrations among the study groups, while the leptin concentration was significantly lower in HIV‑infected lipodystrophic than in nonlipodystrophic patients. CONCLUSIONS HIV infection induces lipid disorders, especially associated with fatty acid turnover augmented by ARV therapy. Compared with FABP4, leptin is a better biological marker of metabolic complications in HIV‑infected patients.
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Normalization of mucosal cytokine gene expression levels predicts long-term remission after discontinuation of anti-TNF therapy in Crohn's disease.
Rismo, R, Olsen, T, Cui, G, Paulssen, EJ, Christiansen, I, Johnsen, K, Florholmen, J, Goll, R
Scandinavian journal of gastroenterology. 2013;(3):311-9
Abstract
OBJECTIVE To investigate mucosal cytokine gene expression levels in healed mucosa after anti-tumor necrosis factor (TNF) therapy in patients with Crohn's disease (CD) as possible risk factors for relapse after discontinuation of therapy. DESIGN Thirty-seven CD patients treated with anti-TNF agents until complete mucosal healing, documented by endoscopy, discontinued anti-TNF treatment and entered a follow-up study. Levels of mRNA expression of interleukin (IL)17A (IL17A), IL23, interferon-gamma (IFNG), TNF-alpha (TNF), IL10 and Forkhead Box P3 (FOXP3) were measured in biopsies from healed mucosa and analyzed as possible risk factors of relapse. Mucosal cytokine transcript levels from patients without CD served as controls. RESULTS Patients were followed after therapy withdrawal until relapse. Median time to relapse was 20 and 68 weeks for patients with elevated and normalized IL17A and TNF expression levels, respectively (p = 0.02 for IL17A and p = 0.003 for TNF, log-rank). Expression levels of TNF, IL17A and FOXP3 were significantly higher in patients who relapsed before 26 weeks than in those who did not relapse, and also higher in patients with relapse before week 52 versus non-relapsers. Elevated expression levels of TNF and IL17A in healed mucosa significantly increased the risk of relapse (HR = 3.4, p = 0.03, sensitivity 80%, specificity 38% and HR = 4.1, p = 0.008, sensitivity 81%, specificity 61%, respectively). CONCLUSIONS Normalization of mucosal gene expression of cytokines after anti-TNF therapy does not occur in all patients with healed mucosa as judged by endoscopy. Normalization of TNF and/or IL17A expression predicts long-term remission.
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No evidence of impaired endothelial function or altered inflammatory state in patients with familial hypercholesterolemia treated with statins.
Hovland, A, Aagnes, I, Brekke, OL, Flage, JH, Lappegård, KT
Journal of clinical lipidology. 2010;(4):288-92
Abstract
BACKGROUND Familial hypercholesterolemia (FH) is associated with an increased risk of premature atherosclerosis. Central in this aspect is enhanced inflammation and endothelial dysfunction. OBJECTIVE We sought to examine inflammatory cytokines and endothelial dysfunction in patients with FH treated with statins (n = 14) compared with healthy control patients (n = 11). METHODS Endothelial function was evaluated by the use of the Endo-PAT® system which measured mean reactive hyperemia index. Fasting blood samples were drawn, and 27 biomarkers in addition to standard laboratory tests were analyzed. RESULTS There were no statistically significant differences between the FH group and the control group regarding age, weight, blood pressure, or body mass index. Endothelial function given as RHI was 1.58 and 1.93 (P = NS) in the control and FH groups, respectively. There were no differences between the groups in tumor necrosis factor-alpha, interleukin (IL-1) beta, IL-1 receptor antagonist, IL-6, IL-10, monocyte chemoattractant protein 1, high-sensitivity C-reactive protein, or any of the other inflammatory markers tested. Furthermore, no significant differences between the groups in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein A, apolipoprotein B, lipoprotein (a), homocysteine, HbA(₁c), platelets, and fibrinogen were found. CONCLUSION Endothelial function assessed by reactive hyperemia index-peripheral arterial tonometry or inflammatory state assessed by soluble inflammatory biomarkers were not different in FH patients on statins compared with healthy control patients.
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Effect of renin-angiotensin-aldosterone system (RAAS) blockade on visfatin levels in diabetic nephropathy.
Eyileten, T, Sonmez, A, Saglam, M, Cakir, E, Caglar, K, Oguz, Y, Vural, A, Yenicesu, M, Yilmaz, MI
Nephrology (Carlton, Vic.). 2010;(2):225-9
Abstract
AIM: Plasma visfatin levels are elevated in diabetic nephropathy in parallel to the severity of proteinuria and glomerular filtration rate. The aim of this study was to find out whether the renin-angiotensin-aldosterone system (RAAS) blockage has any effect on the plasma visfatin levels. METHODS Thirty-two patients with diabetic proteinuria (>500 mg/day) with a normal glomerular filtration rate (GFR) and 33 healthy subjects were enrolled. Patients were treated with ramipril 5 mg daily for 2 months. Proteinuria, GFR, high-sensitivity C-reactive protein (hsCRP), visfatin, flow-mediated dilatation (FMD) and homeostasis model assessment of insulin resistance (HOMA-IR) index measurements were performed both before and after the treatment. RESULTS The plasma visfatin, and hsCRP levels of the patients were significantly higher and the FMD was significantly lower (P < 0.001 for all). The visfatin levels were significantly correlated to FMD, systolic and diastolic blood pressures, proteinuria, eGFR, HOMA-IR and hsCRP. Ramipril treatment resulted in a significant decrease in plasma visfatin, proteinuria, hsCRP, HOMA-IR and increase in FMD (P < 0.001) in patients (P < 0.001 for all). CONCLUSION The present study suggests that plasma visfatin levels are related to the endothelial functions, inflammation and the severity of proteinuria in diabetic nephropathy. Treatment with ramipril causes a significant decrease in visfatin levels along with the improvement of proteinuria, endothelial dysfunction and inflammatory state in diabetic nephropathy.