Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.310
Filtrar
1.
Lancet Diabetes Endocrinol ; 9(4): 212-224, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33662334

RESUMO

BACKGROUND: Type 1 diabetes is characterised by progressive loss of functional ß-cell mass, necessitating insulin treatment. We aimed to investigate the hypothesis that combining anti-interleukin (IL)-21 antibody (for low-grade and transient immunomodulation) with liraglutide (to improve ß-cell function) could enable ß-cell survival with a reduced risk of complications compared with traditional immunomodulation. METHODS: This randomised, parallel-group, placebo-controlled, double-dummy, double-blind, phase 2 trial was done at 94 sites (university hospitals and medical centres) in 17 countries. Eligible participants were adults aged 18-45 years with recently diagnosed type 1 diabetes and residual ß-cell function. Individuals with unstable type 1 diabetes (defined by an episode of severe diabetic ketoacidosis within 2 weeks of enrolment) or active or latent chronic infections were excluded. Participants were randomly assigned (1:1:1:1), with stratification by baseline stimulated peak C-peptide concentration (mixed-meal tolerance test [MMTT]), to the combination of anti-IL-21 and liraglutide, anti-IL-21 alone, liraglutide alone, or placebo, all as an adjunct to insulin. Investigators, participants, and funder personnel were masked throughout the treatment period. The primary outcome was the change in MMTT-stimulated C-peptide concentration at week 54 (end of treatment) relative to baseline, measured via the area under the concentration-time curve (AUC) over a 4 h period for the full analysis set (intention-to-treat population consisting of all participants who were randomly assigned). After treatment cessation, participants were followed up for an additional 26-week off-treatment observation period. This trial is registered with ClinicalTrials.gov, NCT02443155. FINDINGS: Between Nov 10, 2015, and Feb 27, 2019, 553 adults were assessed for eligibility, of whom 308 were randomly assigned to receive either anti-IL-21 plus liraglutide, anti-IL-21, liraglutide, or placebo (77 assigned to each group). Compared with placebo (ratio to baseline 0·61, 39% decrease), the decrease in MMTT-stimulated C-peptide concentration from baseline to week 54 was significantly smaller with combination treatment (0·90, 10% decrease; estimated treatment ratio 1·48, 95% CI 1·16-1·89; p=0·0017), but not with anti-IL-21 alone (1·23, 0·97-1·57; p=0·093) or liraglutide alone (1·12, 0·87-1·42; p=0·38). Despite greater insulin use in the placebo group, the decrease in HbA1c (a key secondary outcome) at week 54 was greater with all active treatments (-0·50 percentage points) than with placebo (-0·10 percentage points), although the differences versus placebo were not significant. The effects diminished upon treatment cessation. Changes in immune cell subsets across groups were transient and mild (<10% change over time). The most frequently reported adverse events included gastrointestinal disorders, in keeping with the known side-effect profile of liraglutide. The rate of hypoglycaemic events did not differ significantly between active treatment groups and placebo, with an exception of a lower rate in the liraglutide group than in the placebo group during the treatment period. No events of diabetic ketoacidosis were observed. One participant died while on liraglutide (considered unlikely to be related to trial treatment) in connection with three reported adverse events (hypoglycaemic coma, pneumonia, and brain oedema). INTERPRETATION: The combination of anti-IL-21 and liraglutide could preserve ß-cell function in recently diagnosed type 1 diabetes. The efficacy of this combination appears to be similar to that seen in trials of other disease-modifying interventions in type 1 diabetes, but with a seemingly better safety profile. Efficacy and safety should be further evaluated in a phase 3 trial programme. FUNDING: Novo Nordisk.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Linfócitos B/fisiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Interleucinas/antagonistas & inibidores , Liraglutida/administração & dosagem , Adulto , Linfócitos B/efeitos dos fármacos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Interleucinas/sangue , Masculino , Adulto Jovem
2.
Int J Immunopathol Pharmacol ; 35: 20587384211005645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33779346

RESUMO

Protective effects of peroxiredoxin 6 (PRDX6) in RIN-m5F ß-cells and of thymulin in mice with alloxan-induced diabetes were recently reported. The present work was aimed at studying the efficiency of thymulin and PRDX6 in a type 1 diabetes mellitus model induced by streptozotocin in mice. Effects of prolonged treatment with PRDX6 or thymic peptide thymulin on diabetes development were evaluated. We assessed the effects of the drugs on the physiological status of diabetic mice by measuring blood glucose, body weight, and cell counts in several organs, as well as effects of thymulin and PRDX6 on the immune status of diabetic mice measuring concentrations of pro-inflammatory cytokines in blood plasma (TNF-α, interleukin-5 and 17, and interferon-γ), activity of NF-κB and JNK pathways, and Hsp90α expression in immune cells. Both thymulin and PRDX6 reduced the physiological impairments in diabetic mice at various levels. Thymulin and PRDX6 provide beneficial effects in the model of diabetes via very different mechanisms. Taken together, the results of our study indicated that the thymic peptide and the antioxidant enzyme have anti-inflammatory functions. As increasing evidences show diabetes mellitus as a distinct comorbidity leading to acute respiratory distress syndrome and increased mortality in patients with COVID-19 having cytokine storm, thymulin, and PRDX6 might serve as a supporting anti-inflammatory treatment in the therapy of COVID 19 in diabetic patients.


Assuntos
MAP Quinase Quinase 4/metabolismo , NF-kappa B/metabolismo , Peroxirredoxina VI , Transdução de Sinais , Fator Tímico Circulante , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , /imunologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/imunologia , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Descoberta de Drogas , Interferon gama/sangue , Interleucinas/sangue , Camundongos , Peroxirredoxina VI/metabolismo , Peroxirredoxina VI/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Fator Tímico Circulante/metabolismo , Fator Tímico Circulante/farmacologia , Fator de Necrose Tumoral alfa/sangue
3.
Artigo em Inglês | MEDLINE | ID: mdl-33656139

RESUMO

Currently, there are no biomarkers for Chikungunya fever (CHIK) in clinical practice that can accurately predict the severity or chronification of the disease. The aim of this study is to evaluate the existing literature on biomarkers related to the severity and chronification of CHIK. In this sense, a systematic review was conducted based on the PRISMA Statement guideline. Articles that described the association of biomarkers with the evolution of the disease (severity or chronification), published until August 20th 2019 were considered eligible. The search was carried out in the PubMed, Scopus, Virtual Health Library (VHL) and Science Direct databases. After searching the databases, 17 articles were added to the review, and after analyzing the articles, several biomarkers were associated with severity, such as increased levels of IL-6, IP-10, IL-1b, MIG, MCP-1, and reduced levels of RANTES and IL-8 or chronification, such as increased levels of IL-6, TNF-α, MCP-1, IL-12, INF-α, IL-13, INF-γ, GM-CSF, CRP, IL-1a, IL-15, Factor VII, IP-10, IL-10, IL-4, IL-1RA, IL-8, MIP-1α, MIP-1ß, ferritin, MIG, ESR, NO, malondialdehyde, and reduced levels of RANTES, ferritin, eotaxin, HGF, IL-27, IL-17A, IL-29, TGF-ß, IL-10, and thiols. IL-6, CRP and TNF-α were included in the meta-analysis to assess the relationship with chronification, although they did not reach statistical significance. It was concluded that several biomarkers showed a relationship with severity and chronification of CHIK; the search for these biomarkers can reveal prognostic factors and important therapeutic targets for the treatment of the disease.


Assuntos
Biomarcadores/sangue , Febre de Chikungunya/diagnóstico , Citocinas/sangue , Febre de Chikungunya/sangue , Humanos , Interleucinas/sangue , Índice de Gravidade de Doença
4.
Nutr. hosp ; 38(1): 121-127, ene.-feb. 2021. tab
Artigo em Inglês | IBECS | ID: ibc-198848

RESUMO

BACKGROUND: açaí is the fruit of the palm tree Euterpe oleracea Martius, which is native to the Amazon region. This fruit has been extensively studied due to its potential effects on human health. Studies have also evaluated the potential effect of açaí on the inflammatory response, but there are still few studies that have assessed this property in humans. OBJECTIVE: in this study we aimed to evaluate the effects of 200 g of açaí pulp consumption per day during four weeks on a rich panel of inflammatory biomarkers. METHODS: a prospective nutritional intervention study was conducted on forty apparently healthy women who consumed 200 g of açaí pulp per day for four weeks. A panel of serum inflammatory markers were evaluated before and after the nutritional intervention, namely, cell adhesion molecules (ICAM-1, IVAM-1, P-selectin, MCP-1, and fractalkine), interleukins (IL-1β, IL-6, IL-8, IL-10, and IL-17) and adipokines (adiponectin, leptin, visfatin, and adipsin). The data were analyzed using paired Student's t-test to evaluate the effect of the intervention using PASW Statistics, version 18.0, and a p-value of < 0.05 was considered significant. RESULTS: four weeks of açaí pulp consumption decreased p-selectin, leptin, and visfatin concentrations in the serum of the participating women. CONCLUSION: these results show that consumption of açaí pulp was able to modulate important biomarkers of the inflammatory process in apparently healthy women


INTRODUCCIÓN: el açaí es el fruto de la palmera Euterpe oleracea Martius, originaria de la región amazónica. Esta fruta ha sido ampliamente estudiada debido a sus posibles efectos sobre la salud humana. Los estudios también han evaluado el efecto potencial del açaí sobre la respuesta inflamatoria, pero todavía hay pocos estudios que hayan evaluado esta propiedad en seres humanos. OBJETIVO: en este estudio, nuestro objetivo ha sido evaluar los efectos del consumo de 200 g de pulpa de açaí por día durante cuatro semanas sobre un rico panel de biomarcadores inflamatorios. MÉTODOS: se ha realizado un estudio prospectivo de intervención nutricional en el que cuarenta mujeres aparentemente sanas han consumido 200 g de pulpa de açaí al día durante cuatro semanas. Se ha evaluado un panel de marcadores inflamatorios séricos antes y después de la intervención nutricional, a saber, moléculas de adhesión celular (ICAM-1, IVAM-1, P-selectina, MCP-1 y fractalquina), interleucinas (IL-1β, IL-6, IL-8, IL-10 e IL-17) y adipocinas (adiponectina, leptina, visfatina y adipsina). Los datos han sido analizados mediante la prueba de la t de Student pareada para evaluar el efecto de la intervención mediante el PASW Statistics, versión 18.0, y todo valor de p < 0,05 se consideró significativo. RESULTADOS: después de cuatro semanas de consumo de pulpa de açaí disminuyeron las concentraciones de p-selectina, leptina y visfatina en el suero de las mujeres participantes. CONCLUSIÓN: estos resultados muestran que el consumo de pulpa de açaí ha sido capaz de modular importantes biomarcadores del proceso inflamatorio en mujeres aparentemente sanas


Assuntos
Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Ingestão de Alimentos , Euterpe , Dietética , Selectina-P/metabolismo , Leptina/metabolismo , Nicotinamida Fosforribosiltransferase/administração & dosagem , Adesão Celular , Biomarcadores , Estudos Prospectivos , Interleucinas/sangue , Antropometria , Adipocinas
5.
Cell Death Dis ; 12(1): 53, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414457

RESUMO

Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(I:C)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(I:C)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections.


Assuntos
/metabolismo , Imunidade Inata/efeitos dos fármacos , Influenza Humana/metabolismo , Interleucinas/farmacologia , Pneumonia/prevenção & controle , Poli I-C/toxicidade , Sistema Respiratório/imunologia , Animais , /virologia , Citocinas/metabolismo , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/imunologia , Influenza Humana/virologia , Interleucina-1/sangue , Interleucinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pneumonia/patologia , Sistema Respiratório/metabolismo , Sistema Respiratório/patologia , /isolamento & purificação
6.
Methods Mol Biol ; 2270: 125-147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33479897

RESUMO

Emerging research suggests that IL-35-producing regulatory B cells accumulate in patients and mouse models of pancreatic cancer, one of the most lethal cancers, characterized by late diagnosis, high mortality, and morbidity. Identification of IL-35-producing B cells can be challenging due to the heterodimeric nature of IL-35 and diversity of cell surface markers that define regulatory B-cell subsets across spectrum of diseases. In this chapter, we describe the methods for the isolation of splenic and tumor-infiltrating murine regulatory B cells and subsequent detection of IL-35 by RT-qPCR and intracellular staining, as well as detection of circulating IL-35 by ELISA. We also describe methods for the detection of IL-35-producing human B cells by flow cytometry, RT-qPCR, and immunofluorescence in the context of pancreatic cancer. This chapter should facilitate the study of regulatory IL-35+ B cells in cancer, autoimmunity, and inflammation.


Assuntos
Linfócitos B/citologia , Citometria de Fluxo/métodos , Interleucinas/análise , Animais , Subpopulações de Linfócitos B/citologia , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Linfócitos B Reguladores/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Interleucina-10/imunologia , Interleucinas/sangue , Camundongos , RNA Mensageiro/análise , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
7.
Diabetes Res Clin Pract ; 171: 108585, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310128

RESUMO

Plasma levels of interleukin (IL)-38 were evaluated in patients with type 2 diabetes (T2DM) and healthy controls. Plasma IL-38 was higher in T2DM patients and positively related to waist/hip ratio, HbA1c, uric acid, liver function tests, triglycerides and total proteins. Patients suffering from diabetic nephropathy had the highest IL-38 levels.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Interleucinas/sangue , Fatores Etários , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino
8.
Cell Prolif ; 54(2): e12968, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33332660

RESUMO

OBJECTIVES: Pre-eclampsia is a leading cause of morbidity and mortality during pregnancy. Although the two forms of this disorder, early- (EOPE) and late-onset of pre-eclampsia (LOPE) are different, the underlying pathology remains elusive. We aim to unravel the difference and to identify novel biomarkers for EOPE and LOPE. MATERIALS AND METHODS: A complete comparison of both placental and peripheral blood transcriptomes was performed to investigate the pathology of pre-eclampsia. Single-cell transcriptomics of the maternal-fetal interface were integrated to identify novel biomarkers for EOPE and LOPE which were further verified at protein or mRNA level in patients. RESULTS: We found that the transcriptomes of placentae from EOPE, but not LOPE, were significantly different from their respective controls. Conversely, the transcriptomes of peripheral blood from LOPE were more different from their controls than EOPE. Importantly, we identified that several classical biomarkers of pre-eclampsia were expressed specifically in extravillous trophoblast and syncytiotrophoblast and only upregulated in EOPE, suggesting they should not be applied to all pre-eclampsia patients in general. We further identified novel biomarkers for EOPE and LOPE from differentially expressed genes (DEGs) of placental and peripheral blood, respectively. The new biomarkers EBI3, IGF2, ORMDL3, GATA2 and KIR2DL4 were experimentally verified with patient blood samples. CONCLUSION: Our data demonstrate distinct pathology of EOPE and LOPE, and uncover new biomarkers that can be applied in diagnosis for pre-eclampsia.


Assuntos
Biomarcadores/metabolismo , Pré-Eclâmpsia/patologia , Transcriptoma , Biomarcadores/sangue , Estudos de Casos e Controles , Biologia Computacional , Feminino , Fator de Transcrição GATA2/sangue , Fator de Transcrição GATA2/metabolismo , Humanos , Interleucinas/sangue , Interleucinas/metabolismo , Transtornos de Início Tardio , Proteínas de Membrana/sangue , Proteínas de Membrana/metabolismo , Antígenos de Histocompatibilidade Menor/sangue , Antígenos de Histocompatibilidade Menor/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Mapas de Interação de Proteínas , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Análise de Célula Única
9.
Medicine (Baltimore) ; 99(52): e23832, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350771

RESUMO

ABSTRACT: Guillain-Barré syndrome (GBS) is an acute autoimmune neurological disorder mainly involving the peripheral nerves. Currently, various cytokines have been shown to be involved in the pathogenesis of GBS. Because of their similar biological structures, interleukin (IL)-36α, IL-36ß, IL-36γ, and IL-36 receptor antagonist (Ra) were all renamed and collectively called IL-36 cytokines. The roles of IL-36 cytokines in GBS currently remain unclear.Forty-two patients with GBS and 32 healthy volunteers were included in our study. Serum IL-36α, ß, γ, and interleukin-36 receptor antagonist (IL-36Ra) levels of patients with GBS in the acute and remission phases and healthy volunteers were measured by enzyme-linked immunosorbent assay (ELISA). In addition, we examined the serum levels of other inflammatory factors that have been shown to be involved in GBS pathogenesis, represented by IL-17 and tumor necrosis factor-α (TNF-α). Furthermore, the correlations between the serum levels of IL-36 cytokines and different clinical data or the serum levels of other inflammatory factors in GBS patients were analyzed.Significantly higher serum IL-36α and IL-36γ levels were measured in the acute phase than in the remission phase and in healthy control (HC) subjects (P < .05), while lower serum IL-36Ra levels were measured in the acute phase than in the remission phase and in HC subjects (P < .05). Serum IL-36α and IL-36γ levels were positively correlated with GBS disability scale scores (GDSs), while serum IL-36Ra levels were negatively correlated with GDSs. Correlation analyses among inflammatory factors showed that serum IL-36α and IL-36γ levels in GBS patients were positively correlated with serum IL-17 and TNF-α levels, while serum IL-36Ra levels were negatively correlated with the levels of these 2 inflammatory factors. Similar results were observed in cerebrospinal fluid (CSF), IL-36α and IL-36γ levels in CSF were positively correlated with GDSs, while IL-36Ra levels in CSF were negatively correlated with GDSs. Additionally, the serum and CSF levels of IL-36α and IL-36γ in the axonal subtype of GBS patients were higher than those in the demyelination subtype.Based on our findings, IL-36 cytokines may be involved in the pathogenesis of GBS and some of these cytokines may help predict the disease severity and other clinical characteristics of GBS.


Assuntos
Síndrome de Guillain-Barré , Interleucina-1/sangue , Interleucinas/sangue , Adulto , Correlação de Dados , Avaliação da Deficiência , Ensaio de Imunoadsorção Enzimática , Feminino , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Interleucina-17/sangue , Masculino , Gravidade do Paciente , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue
10.
Rev Iberoam Micol ; 37(2): 41-46, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041191

RESUMO

Critically ill COVID-19 patients have higher pro-inflammatory (IL-1, IL-2, IL-6, tumor necrosis alpha) and anti-inflammatory (IL-4, IL-10) cytokine levels, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells. This severe clinical situation increases the risk of serious fungal infections, such as invasive pulmonary aspergillosis, invasive candidiasis or Pneumocystis jirovecii pneumonia. However, few studies have investigated fungal coinfections in this population. We describe an update on published reports on fungal coinfections and our personal experience in three Spanish hospitals. We can conclude that despite the serious disease caused by SARS-CoV-2 in many patients, the scarcity of invasive mycoses is probably due to the few bronchoscopies and necropsies performed in these patients because of the high risk in aerosol generation. However, the presence of fungal markers in clinically relevant specimens, with the exception of bronchopulmonary colonization by Candida, should make it advisable to early implement antifungal therapy.


Assuntos
Betacoronavirus , Candidíase Invasiva/epidemiologia , Coinfecção/epidemiologia , Infecções por Coronavirus/epidemiologia , Aspergilose Pulmonar Invasiva/epidemiologia , Pneumonia por Pneumocystis/epidemiologia , Pneumonia Viral/epidemiologia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Infecções por Coronavirus/sangue , Humanos , Interferon gama/sangue , Interleucinas/sangue , Pandemias , Pneumonia Viral/sangue , Espanha/epidemiologia , Fator de Necrose Tumoral alfa/sangue
11.
Blood Adv ; 4(20): 5035-5039, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33075136

RESUMO

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-driven coronavirus disease 2019 (COVID-19) has caused unprecedented human death and has seriously threatened the global economy. Early data suggest a surge in proinflammatory cytokines in patients with severe COVID-19, which has been associated with poor outcomes. We recently postulated that the inflammatory response in patients with severe COVID-19 disease is not inhibited by natural killer (NK) cells, resulting in a "cytokine storm." Here, we assessed the NK-cell functional activity and the associated cytokines and soluble mediators in hospitalized COVID-19 patients. Significantly impaired NK-cell counts and cytolytic activity were observed in COVID-19 patients when compared with healthy controls. Also, cytokines like interleukin 12 (IL12), IL15, and IL21 that are important for NK-cell activity were not detected systematically. Serum concentrations of soluble CD25 (sCD25)/soluble IL2 receptor α (sIL2-Rα) were significantly elevated and were inversely correlated with the percentage of NK cells. Impaired NK-cell cytolytic activity together with other laboratory trends including elevated sCD25 were consistent with a hyperinflammatory state in keeping with macrophage-activation syndrome. Our findings suggest that impaired counts and cytolytic activity of NK cells are important characteristics of severe COVID-19 and can potentially facilitate strategies for immunomodulatory therapies.


Assuntos
Infecções por Coronavirus/imunologia , Citotoxicidade Imunológica , Células Matadoras Naturais/imunologia , Pneumonia Viral/imunologia , Adolescente , Adulto , Idoso , Betacoronavirus/imunologia , Infecções por Coronavirus/sangue , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Subunidade alfa de Receptor de Interleucina-2/sangue , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucinas/sangue , Interleucinas/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Índice de Gravidade de Doença , Adulto Jovem
13.
PLoS One ; 15(8): e0235404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785222

RESUMO

OBJECTIVE: To study the role of selected serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome (PCOS). METHODS: Selected serum inflammatory cytokines were analyzed in the particle cells, which were interfered by berberine, from 78 infertile women who were to be treated with In Vitro Fertilization (IVF) /Intracytoplasmic Sperm Injection-Embryo Transfer (icsi-et). Among them, 49 patients had PCOS infertility, and 29 were non-PCOS patients whose infertility resulted from fallopian tube and male factors. The elisa method was used to detect the changes in the expression levels of inflammatory factors in the cells. The correlations between the serum inflammatory cytokine expression levels and the corresponding clinical hormones were analyzed. The changes in the expression (mRNA and protein) levels of the serum inflammatory cytokines were studied by real-time quantitative PCR and protein printing. Fluorescence microscope and flow cytometry were used to detect the glucose uptake capacity of ovarian granulosa cells in PCOS patients under the action of insulin after berberine. RESULTS: In the PCOS group, IL-17a (P = 0.001), IL-1Ra (P<0.0001), and IL-6 (P = 0.035) were significantly higher than those in the non-PCOS group. In the non-PCOS group, AMH level was negatively correlated with inflammatory cytokines IL-17a (r = -0.819;P = 0.004), IL-1a (r = -0.716;P = 0.0.02), IL-1b (r = -0.678;P = 0.031), IL-2 (r = -0.765;P = 0.01), and IL-8 (r = -0.705;P = 0.023). However, in the PCOS group, AMH levels were not significantly correlated with the levels of the examined inflammatory cytokines. Berberine significantly reduced the expression level of mTOR mRNA (P = 0.001), and increased the expression level of IRS-1 mRNA (P = 0.009) in the PCOS granule cells. CONCLUSION: In this study, we find that the elevated levels of serum inflammatory factors IL-17a, IL-1Ra, and IL-6 cause women to be in a subclinical inflammatory state for a long time. Abnormal changes in inflammatory factors alter their original negative correlations with AMH levels, thereby weakening the metabolism of glycolipids, promoting insulin resistance, destroying the normal ovulation and fertilization system of women, leading to polycystic ovary syndrome characterized by menstrual thinning and abnormal ovulation. Berberine can improve the sensitivity of insulin by regulating the signal pathway of insulin receptor substrate-1 (IRS-1) and mammalian target of rapamycin (mTOR) in PCOS patients and achieve a therapeutic effect of treating PCOS.


Assuntos
Anti-Inflamatórios/uso terapêutico , Berberina/uso terapêutico , Insulina/sangue , Interleucinas/sangue , Síndrome do Ovário Policístico/metabolismo , Adulto , Anti-Inflamatórios/administração & dosagem , Hormônio Antimülleriano/metabolismo , Berberina/administração & dosagem , Células Cultivadas , Feminino , Glicolipídeos/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
14.
Life Sci ; 260: 118245, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32791144

RESUMO

AIMS: Bisphenol A (BPA) has been shown to induce liver fibrosis in rodents. Therefore, this study examined the protective effect of a triple combination of curcumin (Cur), N-acetyl cysteine (NAC) and propolis (Prp) extract against BPA-induced hepatic fibrosis. METHODS: 100 Wistar male rats were equally assigned into 10 groups; one group was designated as control. 10 rats were gavaged with BPA (50 mg/kg/day) for 8 wk and left un-treated (BPA group). The remaining 80 rats were divided into 8 groups, distributed in 2 models. Protective model: rats were daily co-treated with BPA and Cur (100 mg/kg, p.o) or NAC (150 mg/kg, p.o) or Prp (200 mg/kg, p.o) or their combination for 8 wk. Preventive model: rats were daily treated with Cur or NAC or Prp or their combination for 4 wk before BPA administration and then in the same manner as protective model. KEY FINDINGS: Current treatment interventions significantly alleviated BPA-induced hepatic damage and fibrosis. They also restored pro-oxidant/antioxidant balance, shifted cytokine balance towards the anti-inflammatory side, decreasing interleukin-1ß/interleukin-10 ratio. Moreover, these compounds seem to exert anti-apoptotic effects by increasing the immunoexpression of B-cell lymphoma 2 in hepatocytes and decreasing hepatic caspase-3 content. Finally, they ameliorated extracellular matrix turn over through down-regulation of matrix metalloproteinase-9 and up-regulation of tissue inhibitor of matrix metalloproteinase-2 genetic expression. SIGNIFICANCE: Current treatments guarded against BPA-induced hepatic fibrosis due to their antioxidant, anti-inflammatory and anti-apoptotic properties, decreasing extracellular matrix turnover. Interestingly, the triple therapy provided hepatoprotection superior to monotherapy. Besides, prophylactic and concurrent treatments seem to be more effective than concurrent treatments.


Assuntos
Acetilcisteína/administração & dosagem , Compostos Benzidrílicos/toxicidade , Curcumina/administração & dosagem , Cirrose Hepática/prevenção & controle , Fenóis/toxicidade , Própole/administração & dosagem , Acetilcisteína/farmacologia , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Curcumina/farmacologia , Quimioterapia Combinada , Inflamação/sangue , Interleucinas/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Masculino , Própole/farmacologia , Ratos , Ratos Wistar
15.
Medicine (Baltimore) ; 99(31): e21390, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756130

RESUMO

Prior evidence suggested that inflammation and inflammatory cytokines polymorphisms might be essential in the development of coronary heart disease (CHD) and cognitive decline. The following study investigated the associations between interleukin-35 (IL-35) polymorphisms and cognitive decline in CHD patients over a 2-year period.CHD patients were enrolled between January 2015 and January 2016. Cognitive function, including memory, orientation, verbal and attention were assessed using Telephone Interview for Cognitive Status-Modified (TICS-m) during a 2-year follow-up. Genotypes of the single nucleotide polymorphisms (SNPs), including rs2243115, rs568408, rs582054, rs583911, rs428253, rs4740 and rs393581 of IL-35 were examined by MassArray (Sequenom). The differences of TICS-m score between 2-year interval were used to estimate the cognitive decline; linear regression model was used to analyze the association between IL-35 polymorphisms and cognitive decline in CHD patients after a 2-year follow-up.The mean age of study individuals was 60.58 (±7.86) years old. There were 255 (68.5%) males and 117 (31.5%) female patients. The TICS-m scores, including overall cognition score, verbal attention and memory scores gradually decreased over a 2 year follow up period (P < .001, respectively), whereas there was no difference in orientation function score between the 1-year and 2-year follow-up (P = .448). Furthermore, after adjusting for age, sex, history of hypertension(HT) and Diabetes mellitus(DM), smoking, education, Therapy regimen (PCI, CABG, medication) left ventricular ejection fraction (LVEF), and the severity of coronary artery stenosis (Gensini score), no association was found between IL-35 rs2243115, rs568408, rs582054, rs583911, rs428253, rs4740 genotypes and cognitive decline in CHD patients over a 2-year period.Our data reveled that IL-35 polymorphisms was not associated with cognitive decline in CHD patients over a 2-year period. Yet, further studies are needed to confirm the role of cytokine gene polymorphisms in cognitive decline among CHD patients.


Assuntos
Disfunção Cognitiva/sangue , Doença das Coronárias/sangue , Interleucinas/sangue , Idoso , Disfunção Cognitiva/complicações , Doença das Coronárias/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos
16.
PLoS One ; 15(7): e0235859, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687494

RESUMO

In our work, we aim to identify new candidate host biomarkers to discriminate between active TB patients (n = 28), latent infection (LTBI; n = 27) and uninfected (NoTBI; n = 42) individuals. For that, active TB patients and their contacts were recruited that donated serum and saliva samples. A multiplex assay was performed to study the concentration of different cytokines, chemokines and growth factors. Proteins with significant differences between groups were selected and logistic regression and the area under the ROC curve (AUC) was used to assess the diagnostic accuracy. The best marker combinations that discriminate active TB from NoTBI contacts were [IP-10 + IL-7] in serum and [Fractalkine + IP-10 + IL-1α + VEGF] in saliva. Best discrimination between active TB and LTBI was achieved using [IP-10 + BCA-1] in serum (AUC = 0.83) and IP-10 in saliva (p = 0.0007; AUC = 0.78). The levels of TNFα (p = 0.003; AUC = 0.73) in serum and the combination of [Fractalkine+IL-12p40] (AUC = 0.83) in saliva, were able to differentiate between NoTBI and LTBI contacts. In conclusion, different individual and combined protein markers could help to discriminate between active TB and both uninfected and latently-infected contacts. The most promising ones include [IP-10 + IL-7], [IP-10 + BCA-1] and TNFα in serum and [Fractalkine + IP-10 + IL-1α + VEGF], IP-10 and [Fractalkine+IL-12p40] in saliva.


Assuntos
Quimiocina CX3CL1/sangue , Quimiocina CXCL10/sangue , Interleucinas/sangue , Tuberculose Latente/sangue , Tuberculose Pulmonar/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Quimiocina CX3CL1/análise , Quimiocina CXCL10/análise , Feminino , Humanos , Interleucinas/análise , Tuberculose Latente/diagnóstico , Tuberculose Latente/metabolismo , Masculino , Pessoa de Meia-Idade , Saliva/química , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/metabolismo , Fator A de Crescimento do Endotélio Vascular/análise
17.
Medicine (Baltimore) ; 99(28): e20921, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664088

RESUMO

Inflammation is an important pathophysiological process after an acute stroke (AS). Pro- and anti-inflammatory molecules (cytokines and interleukins) are the key players during this mechanism. Emerging evidence indicate that these molecules can serve as biomarkers of stroke progression and outcome and as novel therapeutics agents. The aim of this study is to explore the temporal changes in these molecules and validate them as biomarker of AS progression and neurological outcome.The "Cytokine Registry In Stroke Patients (CRISP)" is a prospective cohort study of 600 AS patients presenting to the tertiary hospital with-in 24 h of the onset of symptoms. Plasma cytokines and interleukins will be collected at admission and 24 h after and will be measured using enzyme-linked immunosorbent assay (ELISA) to evaluate the difference in their variation among different gender, race and ethnicity and their association with various neurological outcomes. The primary exposures are biological sex (male, female) and race/ethnicity. Confounding variables include age, vascular risk factors, infarct size, stroke onset to presentation time, and identified stroke etiologies. Matched controls will be used for the comparison and evaluation of the difference among gender and race/ethnicities.CRISP is a prospective observational study that investigates the role and relationship of molecular biomarkers identifying specific and relevant targets pertinent for monitoring the progression and outcome in AS patients.Trial Registration: The study is registered on ClinicalTrial.gov: https://clinicaltrials.gov/ (NCT03297827).


Assuntos
Isquemia Encefálica/metabolismo , Citocinas/sangue , Interleucinas/sangue , Acidente Vascular Cerebral/metabolismo , Doença Aguda , Biomarcadores/sangue , Isquemia Encefálica/fisiopatologia , Protocolos Clínicos/normas , Progressão da Doença , Ensaio de Imunoadsorção Enzimática/métodos , Grupos Étnicos/estatística & dados numéricos , Feminino , Humanos , Inflamação/metabolismo , Masculino , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo
18.
Proc Natl Acad Sci U S A ; 117(28): 16475-16480, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601180

RESUMO

Autism spectrum disorder (ASD) is characterized by impaired social interactions and communication. The pathogenesis of ASD is not known, but it involves activation of microglia. We had shown that the peptide neurotensin (NT) is increased in the serum of children with ASD and stimulates cultured adult human microglia to secrete the proinflammatory molecules IL-1ß and CXCL8. This process is inhibited by the cytokine IL-37. Another cytokine, IL-38, has been reported to have antiinflammatory actions. In this report, we show that pretreatment of cultured adult human microglia with recombinant IL-38 (aa3-152, 1-100 ng/mL) inhibits (P < 0.0001) NT-stimulated (10 nM) secretion of IL-1ß (at 1 ng/mL) and CXCL8 (at 100 ng/mL). In fact, IL-38 (aa3-152, 1 ng/mL) is more potent than IL-37 (100 ng/mL). Here, we report that pretreatment with IL-38 (100 ng/mL) of embryonic microglia (HMC3), in which secretion of IL-1ß was undetectable, inhibits secretion of CXCL8 (P = 0.004). Gene expression of IL-38 and its receptor IL-36R are decreased (P = 0.001 and P = 0.04, respectively) in amygdala from patients with ASD (n = 8) compared to non-ASD controls (n = 8), obtained from the University of Maryland NeuroBioBank. IL-38 is increased (P = 0.03) in the serum of children with ASD. These findings indicate an important role for IL-38 in the inhibition of activation of human microglia, thus supporting its development as a treatment approach for ASD.


Assuntos
Tonsila do Cerebelo/imunologia , Transtorno do Espectro Autista/imunologia , Interleucinas/imunologia , Microglia/imunologia , Adolescente , Transtorno do Espectro Autista/sangue , Células Cultivadas , Criança , Pré-Escolar , Humanos , Interleucina-16/sangue , Interleucina-16/imunologia , Interleucina-1beta/sangue , Interleucina-1beta/imunologia , Interleucina-8/imunologia , Interleucinas/sangue , Masculino , Neurotensina/sangue , Neurotensina/imunologia
19.
Rev. iberoam. micol ; 37(2): 41-46, abr.-jun. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-195350

RESUMO

Critically ill COVID-19 patients have higher pro-inflammatory (IL-1, IL-2, IL-6, tumor necrosis alpha) and anti-inflammatory (IL-4, IL-10) cytokine levels, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells. This severe clinical situation increases the risk of serious fungal infections, such as invasive pulmonary aspergillosis, invasive candidiasis or Pneumocystis jirovecii pneumonia. However, few studies have investigated fungal coinfections in this population. We describe an update on published reports on fungal coinfections and our personal experience in three Spanish hospitals. We can conclude that despite the serious disease caused by SARS-CoV-2 in many patients, the scarcity of invasive mycoses is probably due to the few bronchoscopies and necropsies performed in these patients because of the high risk in aerosol generation. However, the presence of fungal markers in clinically relevant specimens, with the exception of bronchopulmonary colonization by Candida, should make it advisable to early implement antifungal therapy


Los pacientes gravemente enfermos con COVID-19 presentan concentraciones más elevadas de citoquinas pro-inflamatorias (IL-1, IL-2, IL-6 y factor de necrosis tumoral alfa) y anti-inflamatorias (IL-4 e IL-10), menor expresión de interferón-gama y un número más bajo de células CD4 y CD8. Esta grave situación clínica aumenta el riesgo de padecer coinfecciones fúngicas, como la aspergilosis pulmonar invasora, la candidiasis invasora o la neumonía por Pneumocystis jirovecii. Sin embargo, pocos estudios han investigado las coinfecciones fúngicas en esta población. En esta revisión describimos una actualización de las publicaciones sobre coinfecciones fúngicas en esta población de pacientes y nuestra experiencia personal en tres hospitales españoles. Podemos concluir que a pesar de la grave enfermedad causada por el SARS-CoV-2 en muchos pacientes, la baja frecuencia de micosis invasoras se debe probablemente a las pocas broncoscopias y necropsias realizadas en estos pacientes debido al alto riesgo de producción de aerosoles. Sin embargo, la presencia de marcadores fúngicos en muestras clínicas relevantes, con la excepción de la colonización broncopulmonar por Candida, debería aconsejar la instauración precoz de una terapia antifúngica


Assuntos
Humanos , Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Candidíase Invasiva/epidemiologia , Coinfecção , Aspergilose Pulmonar Invasiva/epidemiologia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Interferon gama/sangue , Interleucinas/sangue , Fator de Necrose Tumoral alfa/sangue
20.
Infect Dis Poverty ; 9(1): 47, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381058

RESUMO

BACKGROUND: The incidence of brucellosis, which is caused by the Brucella species of bacteria, is rapidly rising worldwide; however, few studies have investigated the immune response to this pathogen and clinical biochemical features. In this paper, we examined the levels of various cytokines and inflammatory factors as well as clinical course characteristics in patients with brucellosis, in order to provide evidence for the diagnosis, assessment, and prognosis of this infectious disease. METHODS: A total of 191 brucellosis inpatients (50 acute cases and 141 chronic cases), as well as 60 healthy control subjects, were included in the analysis. We investigated changes in the levels of six cytokines (IL-4, IL-6, IL-10, IL-17, TNF-α, INF-γ) and related clinical biochemical markers in patients with acute and chronic brucellosis in Xinjiang, China. Possible factors were statistically analyzed using the t test, χ2 test, z test and a multivariate logistic stepwise regression test. RESULTS: We found that IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α levels were higher in those with brucellosis than in controls (P <  0.05). With regard to disease progression, procalcitonin (PCT) and C-reactive protein (CRP) levels were significantly higher in those with an acute infection compared to chronic cases (P <  0.05). We found that the expression of all six cytokines tested was closely related to the degree of brucellosis using univariate logistic regression; however, only IL-6 and INF-γ levels were independent factors associated with the severity of brucellosis. CONCLUSIONS: Assessing cytokine levels in patients with acute and chronic brucellosis is not only useful for detecting the immune response, but can also be indicative of the severity of brucellosis. In particular, we propose IL-6 and INF-γ levels may be useful independent predictive factors in the clinical evaluation and diagnosis of brucellosis.


Assuntos
Brucelose/diagnóstico , Interferons/sangue , Interleucinas/sangue , Adolescente , Adulto , Idoso , Brucelose/sangue , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...