Objective: In recent years, the role of the modern inflammatory markers TREM-1 (triggering receptors expressed on myeloid cells) and HMGB1 (high mobility group box 1 protein) in tumorigenesis has begun to be studied. Their role in gliomas is not clear. The aim of our study was to find the role of inflammation in gliomas. Patients and Methods. In 63 adult patients with gliomas and 31 healthy controls, the expressions of TREM-1 and TREM-2 on CD14+ blood cells (method: flow cytometry) and the levels of soluble sTREM-1, HMGB1, IL-6, and IL-10 (Elisa tests) were analyzed. Results: Cox proportional hazard analysis showed that a TREM-1/TREM-2 ratio was associated with reduced overall survival (HR = 1.001, P = 0.023). Patients with a TREM-1/TREM-2 ratio above 125 survived significantly shorter than patients with a TREM-1/TREM-2 ratio below 125. The percentage of CD14+ TREM-1+ cells was strongly associated with a plasma IL-6/IL-10 ratio (positively) and with IL-10 (negatively). Conversely, we found a higher percentage of CD14+ TREM-2+ monocytes in better surviving patients; these cells could downregulate the exaggerated inflammation and potentiate the phagocytosis in the tumor. The serum levels of HMGB1 negatively correlated with the percentage of CD14+ TREM-1+ cells and with the TREM-1/TREM-2 ratio. The positive correlation between the serum levels of a late proinflammatory cytokine HMGB1 with the percentage of TREM2+ CD14+ monocytes can be explained as an effort for suppression of systemic inflammation by anti-inflammatory acting CD14+ TREM-2+ cells. Conclusion: We showed that the TREM-1/TREM-2 ratio (expression on the surface of blood monocytes) could help predict prognosis in patients with gliomas, especially in high-grade gliomas, and that systemic inflammation has an impact on the patient's overall survival. This is the first study that showed that TREM expression on monocytes in peripheral blood could help predict prognosis in patients with gliomas.
- MeSH
- dospělí MeSH
- gliom krev metabolismus mortalita MeSH
- interleukin-10 krev MeSH
- interleukin-6 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipopolysacharidové receptory metabolismus MeSH
- membránové glykoproteiny metabolismus MeSH
- monocyty metabolismus MeSH
- proporcionální rizikové modely MeSH
- protein HMGB1 krev MeSH
- receptor TREM-1 metabolismus MeSH
- receptory imunologické metabolismus MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIM: To evaluate the effects of orally administered gadolinium orthovanadate GdVO4:Eu3+ nanoparticles (VNPs) on the course of chronic carrageenan-induced intestinal inflammation. METHODS: Samples of small intestinal tissue were collected from four groups of rats (intact, after administration of VNPs, with carrageenaninduced intestinal inflammation, with carrageenan-induced intestinal inflammation orally exposed to VNPs) to assess the intestinal morphology and HSP90α expression. Levels of seromucoid, C-reactive protein, TNF-α, IL-1β and IL-10 were determined in blood serum. RESULTS: Oral exposure to VNPs was associated with neither elevation of inflammation markers in blood serum nor HSP90α overexpression in the small intestine, i.e. no toxic effects of VNPs were observed. Carrageenan-induced intestinal inflammation was accompanied by higher levels of TNF-α and IL-1β, as well as HSP90α upregulation in the intestinal mucosa, compared with controls. Administration of VNPs to rats with enteritis did not lead to statistically significant changes in concentrations of circulating pro-inflammatory cytokines with the trend towards their increase. CONCLUSION: No adverse effects were observed in rats orally exposed to VNPs at a dose of 20 μg/kg during two weeks. Using the experimental model of carrageenan-induced enteritis, it was demonstrated that VNPs at the dose used in our study did not affect the course of intestinal inflammation.
- MeSH
- C-reaktivní protein účinky léků metabolismus MeSH
- enterokolitida krev chemicky indukované patologie MeSH
- gadolinium farmakologie MeSH
- idiopatické střevní záněty krev patologie MeSH
- interleukin-10 krev MeSH
- interleukin-1beta krev účinky léků MeSH
- karagenan toxicita MeSH
- kovové nanočástice * MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- orosomukoid účinky léků metabolismus MeSH
- proteiny tepelného šoku HSP90 účinky léků metabolismus MeSH
- scavengery volných radikálů farmakologie MeSH
- střevní sliznice účinky léků metabolismus patologie MeSH
- TNF-alfa krev účinky léků MeSH
- vanadáty farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: MiR150-5p has been reported to be involved in generalized myasthenia gravis, in which different cytokines play critical roles. The regulatory network of cytokines in generalized myasthenia gravis has not been fully elucidated. Our study aimed to investigate the interactions between miR150-5p and different cytokines in generalized myasthenia gravis. MATERIALS AND METHOD: Serum levels of miR150-5p and different cytokines including IL-2, IL-17, IL-10, IL-19, IL-20 and IL-35 were detected by qRT-PCR and ELISA, respectively. ROC curve analysis was performed to evaluate the diagnostic value of miR150-5p for generalized myasthenia gravis. Correlation between serum levels of miR150-5p and different cytokines were analyzed by Pearson correlation coefficient. RESULTS: Compared with healthy controls, decreased serum levels of IL-2 and IL-17 and increased serum levels of miR150-5p, IL-10, IL-19, IL-20 and IL-35 were observed in patients with generalized myasthenia gravis. Serum levels of miR150-5p were positively correlated with IL-10 and negatively correlated with IL-17. After treatments, serum levels of miR150-5p and IL-10 decreased, while serum levels of IL-2 and IL-17 increased. CONCLUSION: Upregulation of miR150-5p is involved in generalized myasthenia gravis patients and is associated with decreased serum levels of IL-17 as well as increased serum levels of IL-10.
- MeSH
- dospělí MeSH
- interleukin-10 krev MeSH
- interleukin-17 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- mladý dospělý MeSH
- myasthenia gravis krev genetika MeSH
- ROC křivka MeSH
- studie případů a kontrol MeSH
- upregulace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Several pathophysiological mechanisms have been proposed in the development of pregnancy complications, including endothelial dysfunction, an inflammatory pathway and oxidative stress. The aim of the present study was to evaluate the correlation between proinflammatory cytokines TNF-alpha, IL-6 and dual cytokine IL-10 in the mother's peripheral blood and systolic blood pressure, risk of preeclampsia and low birth weight in gestational diabetes (GDM). We observed 40 women with GDM divided into a gestational hypertension group (n=20) and comparison group (n=20) with normal blood pressure. We found a significant positive correlation between TNF-alpha; IL-6; IL-10 levels and systolic blood pressure (SBP) in the second trimester (p<0.001; p<0.001; p<0.001); the third trimester (p<0.001; p<0.001; p<0.05). We also proved correlations for diastolic blood pressure (DBP) during the second; third trimester (p<0.001; p<0.001; p<0.001); (p<0.001; p<0.001; p<0.0015). We demonstrated a statistically significant positive association between high TNF-alpha group and preeclampsia risk in the third trimester (p=0.04). We also determined the negative correlation in the second trimester between birth weight and TNF-alpha; IL-6, IL-10 levels (p<0.05; p<0.001; p<0.001). To conclude, our data highlight the importance of cytokines TNF-alpha, IL-6 and IL-10 in blood pressure regulation. In addition, high levels of TNF-alpha have been associated with increased risk of preeclampsia. We found a significant negative correlation between levels of TNF-alpha, IL-6, IL-10 and birth weight.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- gestační diabetes krev diagnóza MeSH
- interleukin-10 krev MeSH
- interleukin-6 krev MeSH
- krevní tlak fyziologie MeSH
- lidé MeSH
- novorozenec s nízkou porodní hmotností krev MeSH
- novorozenec MeSH
- preeklampsie krev diagnóza MeSH
- rizikové faktory MeSH
- těhotenství MeSH
- TNF-alfa krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The growing knowledge of the key role of microbiota in the maturation of neonatal immune system suggests that manipulation of microbiota could be exploited in hampering allergy development. In this study, Escherichia coli O83:K24:H31 (EcO83) was administered to newborns that were followed prospectively. Several immunological characteristics (cytokines, specific IgE, total T regulatory cells (Treg) and subpopulation of natural Treg (nTreg) and induced Treg (iTreg)) were tested in peripheral blood of 8-year-old children. Incidence of allergic disease was decreased in EcO83 supplemented children and significantly elevated levels of IL-10 and IFN-ɣ were detected in serum of EcO83 supplemented children. Probiotic supplementation did not influence the numbers of the total Treg population but their functional capacity (intracellular expression of IL-10) was significantly increased in children supplemented with EcO83 in comparison to non-supplemented children. Morover, decreased proportion of iTreg was present in peripheral blood of non-supplemented in comparison to EcO83 supplemented children. Finally, stimulation of cord blood cells with EcO83 promoted both gene expression and secretion of IL-10 and IFN-ɣ suggesting that beneficial effect of EcO83 in prevention of allergy development could be mediated by promotion of regulatory responses (by IL-10) and Th1 immune response (by IFN-ɣ).
- MeSH
- alergie epidemiologie imunologie MeSH
- dítě MeSH
- Escherichia coli fyziologie MeSH
- fetální krev cytologie imunologie mikrobiologie MeSH
- imunitní systém MeSH
- incidence MeSH
- interferon gama krev MeSH
- interleukin-10 krev MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikrobiota imunologie MeSH
- novorozenec MeSH
- probiotika terapeutické užití MeSH
- prospektivní studie MeSH
- regulační T-lymfocyty imunologie MeSH
- Th1 buňky imunologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Probiotics are believed to prevent or reduce allergy development but the mechanism of their beneficial effect is still poorly understood. Immune characteristics of regulatory T cells (Tregs) in peripheral blood of perinatally probiotic-supplemented children of allergic mothers (51 children), non-supplemented children of allergic mothers (42 children), and non-supplemented children of healthy mothers (28 children) were compared at the age of 6-7 years. A first dose of a probiotic Escherichia coli strain (E. coli O83:K24:H31) was administered within 2 days after the birth and then 12 times during the first months of life and children were followed longitudinally. Proportion and functional properties of Tregs were estimated by flow cytometry in relation to the children's allergy status. Proportion of Tregs in the peripheral blood of children suffering from allergy tends to be higher whereas median of fluorescence intensity (MFI) of FoxP3 was significantly decreased in allergic group. Intracellular presence of regulatory cytokine interleukin (IL)-10 was also lower in allergic children. Immune functions of Tregs reflected by both MFI of FoxP3 and IL-10 in the group of probiotic-supplemented children of allergic mothers were nearly comparable with children of healthy mothers while probiotic non-supplemented children of allergic mothers have decreased immune function of Tregs. Supplementation by probiotic E. coli strain decreases allergy incidence in high-risk children. In contrast to our expectation, proportion of Tregs has not been increased in probiotic supplemented children. Beneficial effect of probiotics on newborn immature immune system could be, at least partially, explained by the modulating immune function of Tregs. In summary, we detected increased proportion of Tregs in peripheral blood of allergic children, their functional properties were decreased in comparison with the Tregs of healthy children. A unifying hypothesis for these findings is that Treg numbers in allergic children are increased in order to compensate for decreased function.
- MeSH
- alergie prevence a kontrola MeSH
- cytokiny krev imunologie MeSH
- dítě MeSH
- Escherichia coli * MeSH
- interleukin-10 krev imunologie MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- probiotika aplikace a dávkování MeSH
- průtoková cytometrie MeSH
- regulační T-lymfocyty imunologie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cíl: Proveřit možnost monitorace efektu anti TNFα terapie u pacientů léčených pro revmatoidní artritidu pomocí multiplexového stanovení sérových hladin vybraných biomarkerů odrážejících základní patofyziologické mechanizmy a aktivitu onemocnění. Metody: Byla hodnocena skupina 23 pacientů s aktivní revmatoidní artritidou, z toho 20 žen, 3 muži, průměrný věk 48,6 ± 10,3 let, průměrná hmotnost 68,5 ± 13 kg před léčbou a po 14–16 týdnech léčby s inhibitorem TNFα adalimumabem 40 mg subkutánně podávaným jednou za dva týdny (N = 21) nebo etanerceptem 25 mg podávaným podkožně dvakrát týdně (N= 2). Z 23 pacientů, 16 (70 %) užívalo současně s glukokortikoidy (GC) a 19 subjektů (84 %) methotrexát. Krev byla odebrána ze žíly pomocí odběrové zkumavky Vacuette (Greiner Bio One, Rakousko). Krevní vzorky byly odstřeďeny při 640 g po dobu 10 min. Sérum bylo rozděleno na alikvoty a zamraženo do provedení analýzy při teplotě -75 °C. Sérové hladiny IL 1β, IL10, IL6, VEGF, MMP9 a adiponektinu byly stanoveny multiplexovou analýzou pomocí technologie XMAP komerčním kitem Human Cardiovascular 1, Lineo Research (USA) podle návodu výrobce k použití. Analýza byla provedena na přístroji Luminex 100 a analýza dat pomocí Luminex 100 IS software verze 2.3. Tyto parametry byly korelovány s krevními hladinami CRP, PCT, TK (stanoveno radioenzymaticky), hmotností pacienta a DAS-28. Pro všechny parametry byl vypočten průměr, medián, směrodatná odchylka, minimální a maximální hodnoty z výsledků před a po terapii. Data byla analyzována Wilcoxonovým párovým testem a koeficientem pořadové korelace. Výsledky: Potvrdili jsme statisticky signifikantní snížení hladiny CRP (p = 0,001), VEGF (p = 0,05) a adiponektinu (p = 0,05), aktivity onemocnění hodnocené pomocí DAS-28 (p = 0,001) a významné zvýšení hmotnosti po léčbě (p = 0,01). Pokles hodnot všech tří prozánětlivých interleukinů nebyl významný. Závěry: Naše pilotní studie prokázala potencionální využitelnost i limity multiplexové analýzy cytokinů a některých dalších biomarkerů v monitorování léčby revmatoidní artritidy. Ke stanovení doporučení pro rutinní klinickou praxi je nezbytné zvolit vhodnější panel a rozšířit skupinu pacientů.
Methods: A group of 23 patients with active rheumatoid arthritis, 20 female, 3 male, average age 48.6 years ± 10.3, average weight 68,5 ± 13 kg was evaluated prior therapy and after 14–16 weeks of therapy with TNFα blocking agent adalimumab 40 mg subcutaneously every two weeks (No = 21) and etanercept 25 mg subcutaneously twice weekly (No = 2). Of 23 patients, 16 (70 %) of subject were treated concomitantly with glucocorticoids (GC), and 19 subject ( 84 %) with methotrexate. The blood was collected by venipuncture using Vacuette collection tubes (Greiner Bio-One, Austria). The blood samples were centrifuged at 640 g for 10 min, serum was aliquoted and stored until analysed in freezer at -75 °C. Serum levels of six parameters: IL 1β, IL10, IL6, VEGF, MMP9 and adiponectin were assessed by multiplex immunoanalysis using xMAP technology with commercially available multiplex kits Human Cardiovascular 1 panel and Human Cytokines-Chemokines panel, both from Linco Research (USA) according to manufacturer‘s instructions for use. The analysis was performed on Luminex 100 instrument and data analysis on Luminex 100 IS software version 2.3. These parameters were correlated with blood levels of CRP, PCT, TK (assessed by traditional immunoassays), patient weight and DAS-2828. For all parameters there was counted average, median, standard deviation, minimal and maximal values from results prior and after therapy. Furthermore, data were analysed by Wilcoxon pair test and Rank-order correlation. Results: We confirmed significantly decreased CRP levels (p = 0,001), VEGF(p = 0,05) and adiponectin (p = 0,05), disease activity score DAS-28 (p = 0,001) and significant increase of weight after therapy (p = 0,01). Decrease of all of three proinflammatory interleukins were not significant. Conclusions: Our pilot study showed the usefulness and limitations of multiplex measurements of cytokines and some other biomarkers in monitoring of rheumatoid arthritis therapy. But to establish guidelines for the routine clinical practice it is necessary to select preferable panel and to enlarge a group of the patients.
- MeSH
- adalimumab terapeutické užití MeSH
- adiponektin krev MeSH
- biologické markery * krev MeSH
- C-reaktivní protein analýza MeSH
- dospělí MeSH
- etanercept terapeutické užití MeSH
- interleukin-10 krev MeSH
- interleukin-1beta krev MeSH
- interleukin-6 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 9 krev MeSH
- neparametrická statistika MeSH
- pilotní projekty MeSH
- revmatoidní artritida * farmakoterapie krev MeSH
- TNF-alfa antagonisté a inhibitory MeSH
- vaskulární endoteliální růstové faktory krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
AIM: The aim of the present study was to evaluate the usefulness of four interleukins (IL-2, IL-6, IL-8 and IL-10) for melanoma detection and correlate these interleukins with sentinel node metastasis positivity. PATIENTS AND METHODS: A group of 236 persons was assessed: 175 patients with melanomas and 61 healthy persons. Melanoma patients were divided to four groups according to Breslow score. We determined IL-2, IL-6, IL-8 and IL-10 in each plasma sample. Interleukin plasma levels were assayed using a Human Cytokine Milliplex Map kit. Measurements were performed using the Bio-Plex MAGPIX Multiplex Reader. Plasma samples were collected prior to surgery or any other form of treatment. All melanoma diagnoses were histologically verified. RESULTS: We compared interleukin plasma levels in the healthy group and plasma levels in each Breslow score stage. In the first Breslow score stage, IL-2 (p<0.0001), IL-6 (p=0.0004) and IL-10 (p<0.0001) were positive. In the second Breslow score, stage IL-2 (p<0.0001), IL-6 (p<0.0001), IL-8 (p=0.0017) and IL-10 (p<0.0001) were positive. By comparing the group of positive and negative sentinel node metastasis, we observed a statistically significant difference in two interleukins: The median of IL-2 levels in the negative group was 5.88 pg/ml compared to 32.57 pg/ml in the positive group (p=0.0005). The median of IL-6 levels in the negative group was 4.80 pg/ml compared to 32.02 pg/ml in the positive group (p=0.0048). CONCLUSION: Interleukins IL-2, IL-6 and IL-10 are promising biomarkers of early-stage melanoma. IL-2 and IL-6 appear to be prognostic biomarkers.
- MeSH
- biopsie sentinelové lymfatické uzliny MeSH
- časná detekce nádoru MeSH
- dospělí MeSH
- interleukin-10 krev MeSH
- interleukin-2 krev MeSH
- interleukin-6 krev MeSH
- interleukin-8 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- melanom krev patologie MeSH
- mladiství MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- adiponektin * krev MeSH
- chronické selhání ledvin * krev mortalita MeSH
- dialýza ledvin * mortalita MeSH
- index tělesné hmotnosti MeSH
- interleukin-10 krev MeSH
- interleukin-6 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- proporcionální rizikové modely MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- komentáře MeSH
According to recent trials, a significant number of patients do not have a completely effective response to clopidogrel. The aim of the study was to evaluate the rate of clopidogrel resistance in the context of important clinical characteristics and to specifically determine the relation between clopidogrel efficacy and biomarkers of inflammation. Consecutive non-selected patients following PCI were enrolled into the study. All patients received a loading dose of 600 mg of clopidogrel. The effect of clopidogrel was assessed using the VerifyNow assay 24 h after clopidogrel administration, clopidogrel resistance was defined as PRU ≥ 240. At the same time, standard parameters of biochemistry and hematology, the concentration of anti-inflammatory cytokine interleukin-10 and of soluble CD40 ligand, were measured. 378 patients were enrolled. 243 (64.3%) patients were responders (R) and 135 patients (35.7%) were non-responders (NR). Non-responders were older (R 65.7 ± 13.3, NR 69.8 ± 11.5, P < 0.05), had a higher prevalence of diabetes (R 26.3%, NR 38.5%, P < 0.05), were more often on mechanical ventilation (R 0.8%, NR 4.4%, P < 0.05). The leukocyte count (R 9.8 ± 3.5, NR 11.7 ± 12.8, P < 0.05), and concentration of IL-10 (R 3.1 pg/ml, NR 5.7 pg/ml, P < 0.05) was higher among non-responders. The concentration of CD40L was not significantly different between the groups. In a multivariate logistic regression, older age, higher weight, female gender, mechanical ventilation, and a higher concentration of leukocytes and IL-10 were associated with an increased risk for being a non-responder. Older, obese patients, especially women had a higher risk of high on-treatment-platelet-reactivity. Higher concentrations of leukocytes and interleukin-10 were also an important factor associated with the risk of low clopidogrel responsiveness.
- MeSH
- biologické markery krev MeSH
- diabetes mellitus krev farmakoterapie MeSH
- inhibitory agregace trombocytů aplikace a dávkování MeSH
- interleukin-10 krev MeSH
- léková rezistence MeSH
- lidé středního věku MeSH
- lidé MeSH
- ligand CD40 krev MeSH
- počet leukocytů MeSH
- senioři MeSH
- tiklopidin aplikace a dávkování analogy a deriváty MeSH
- věkové faktory MeSH
- zánět MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH