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1.
Biomedica ; 41(Sp. 2): 86-102, 2021 10 15.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34669281

RESUMO

INTRODUCTION: Immunological markers have been described during COVID-19 and persist after recovery. These immune markers are associated with clinical features among SARSCoV-2 infected individuals. Nevertheless, studies reporting a comprehensive analysis of the immune changes occurring during SARS-CoV-2 infection are still limited. OBJECTIVE: To evaluate the production of proinflammatory cytokines, the antibody response, and the phenotype and function of NK cells and T cells in a Colombian family cluster with SARS-CoV-2 infection. MATERIALS AND METHODS: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. The frequency, phenotype, and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with spike/RdRp peptides) were assessed by flow cytometry. Anti-SARS-CoV-2 antibodies were determined using indirect immunofluorescence and plaque reduction neutralization assay. RESULTS: During COVID-19, we observed a high proinflammatory-cytokine production and a reduced CD56bright-NK cell and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by high IL-10 production. However, during recovery, we observed a bifunctional response characterized by the co-expression of CD107a and granzyme B or perforin. CONCLUSION: Although the proinflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and to guide future immunotherapy strategies.


Assuntos
COVID-19/imunologia , Células Matadoras Naturais , SARS-CoV-2/imunologia , Linfócitos T , Adulto , Anticorpos Antivirais/análise , Antígeno CD56/imunologia , Estudos de Casos e Controles , Colômbia , Saúde da Família , Granzimas/metabolismo , Humanos , Interleucina-10/metabolismo , Interleucina-1beta/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Células K562 , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Perforina/metabolismo , Fenótipo , Receptores CCR7/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
2.
Iran J Med Sci ; 46(5): 373-382, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34539012

RESUMO

Background: Acute liver failure (ALF) is a fatal clinical situation that rapidly leads to the loss of normal liver function. Esculetin is a natural herbal compound used for the management of various diseases such as cardiovascular and renal disorders. In this study, we evaluated the protective effects of esculetin in a mouse model of ALF. Methods: This article is a report on an experimental study that was conducted at Iran University of Medical Sciences in 2019. Forty-eight male C57BL/6 mice were randomly divided into control, LPS/D-Gal, and LPS/D-Gal+Esculetin (40 mg/kg) groups (n=16 per group). ALF was induced with an intraperitoneal injection of lipopolysaccharide (LPS)/D-galactosamine (D-Gal).The LPS/D-Gal group received a mixture of LPS (50 µg/kg) and D-Gal (400 mg/kg). The LPS/D-Gal+Esculetin group received esculetin by gavage 24 hours and one hour before receiving LPS/D-Gal. Six hours after LPS/D-Gal injection, the mice were sacrificed. Liver injury markers, including alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP), were measured in the serum. Oxidative stress indices and inflammatory markers such as interleukin-1 beta (IL-1ß), IL-6, and tumor necrosis factor-alpha (TNF-α) were measured in hepatic tissue. The histopathology of liver tissue was also assessed. The data were analyzed using one-way ANOVA, followed by the post hoc Tukey test. Results: Esculetin lowered oxidative stress and myeloperoxidase activity (P<0.001); reduced the serum levels of ALT (P=0.037), AST (P=0.032), and ALP (P=0.004); and decreased the hepatic levels of IL-1ß (P=0.002), IL-6 (P=0.004), toll-like receptor 4 (P<0.001), TNF-α (P=0.003), and nuclear factor-kappa B (P<0.001) as compared with LPS/D-Gal. Additionally, esculetin ameliorated hepatic tissue injury following LPS/D-Gal challenge. Conclusion: Esculetin can reduce liver injury through the mitigation of oxidative burden, inflammation, and neutrophil infiltration and also exerts hepatoprotective effects against ALF.


Assuntos
Galactosamina/farmacologia , Lipopolissacarídeos/farmacologia , Falência Hepática Aguda/tratamento farmacológico , Umbeliferonas/farmacologia , Animais , Modelos Animais de Doenças , Galactosamina/uso terapêutico , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-6/análise , Interleucina-6/sangue , Irã (Geográfico) , Lipopolissacarídeos/uso terapêutico , Falência Hepática Aguda/patologia , Falência Hepática Aguda/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/sangue , Fatores de Proteção , Receptor 4 Toll-Like/análise , Receptor 4 Toll-Like/sangue , Umbeliferonas/uso terapêutico
3.
Biol Psychol ; 165: 108147, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34492333

RESUMO

Although elevations in systemic suPAR levels have been associated with inflammatory conditions and with exposure to life stress and adversity, it is not yet clear whether acute psychological stress influences suPAR levels, either systemically and/or in saliva. The aim of this study was to investigate whether salivary suPAR levels are increased following exposure to acute psychological stress. Healthy subjects, aged 18-40 years, completed a laboratory psychological stressor and provided saliva samples before and after the stress test (60 min apart). Levels of suPAR as well as those of cytokines increased in the post-stress samples (all ps < .001). Baseline and post-stress IL-1ß and TNF-α as well as post-stress IL-6 correlated significantly with suPAR (all ps < .01), but IL-10 and baseline IL-6 did not. These results show that suPAR levels in saliva are stress-reactive and suggest a potential application as stress biomarkers in saliva, particularly given the advantage of easily detectable concentrations.


Assuntos
Receptores de Ativador de Plasminogênio Tipo Uroquinase , Saliva , Estresse Psicológico , Biomarcadores , Humanos , Interleucina-10/sangue , Interleucina-10/fisiologia , Interleucina-1beta/sangue , Interleucina-1beta/fisiologia , Interleucina-6/sangue , Interleucina-6/fisiologia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/fisiologia , Fator de Necrose Tumoral alfa/sangue
4.
PLoS One ; 16(9): e0257507, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34543351

RESUMO

Inflammation contributes to knee osteoarthritis (KOA) where many immunological mediators participate in its initiation and progression. Most clinicians manage primary (pKOA) and secondary osteoarthritis (sKOA) alike. Whether immunological profiles of pKOA and sKOA differ remains obscure. Hence, we aimed to differentially identify potential serum immunologic diagnostic markers of pKOA and of sKOA. This case control study used 46 KOA patients (pKOA, n = 30; sKOA, n = 16), and 60 age, gender matched controls (normal healthy, n = 30; systemic lupus erythematosus [SLE] disease controls, n = 30) where serum was assayed for cytokines (TNF-α, IL-1ß, IL-6, IL-10) and nitric oxide derivatives (NOx). Sandwich ELISA assessed cytokine levels, while the 'Griess assay' quantified NOx levels. The diagnostic accuracy of optimal marker combinations was evaluated by the CombiROC web tool. Compared with pKOA, sKOA serum displayed significantly elevated levels of pro inflammatory cytokines (TNF-α, IL-1ß, IL-6) with a concurrent decrease in the anti-inflammatory cytokine, IL-10 (P<0.05). This was reiterated by significantly higher Th1:Th2 (TNF-α: IL-10) serum cytokine ratio observed in sKOA compared to that of pKOA. The CombiROC curves identified TNF-α, IL-1ß, IL-6 and NOx as the best performing panel of potential diagnostic markers to discriminate pKOA from control groups (~97% accuracy, 90% Sensitivity [SE] and 98% specificity [SP]), while TNF-α, IL-1ß and IL-6 discriminated sKOA from control groups (~100% accuracy, 100% SE, and 98% SP). The study identified discrete serum immune biomarker panels to differentiate between pKOA (TNF-α, IL-1ß, IL-6 and NOx) and sKOA (TNF-α, IL-1ß and IL-6). These findings may assist in developing distinct therapeutic agents for the two types of KOA.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Osteoartrite do Joelho/diagnóstico , Área Sob a Curva , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-10/sangue , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/análogos & derivados , Óxido Nítrico/sangue , Osteoartrite do Joelho/imunologia , Curva ROC , Sensibilidade e Especificidade , Fator de Necrose Tumoral alfa/sangue
5.
PLoS One ; 16(9): e0257214, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34506568

RESUMO

Our earlier studies in tuberculosis (TB) patients indicate that in those where the process evolves to a larger pulmonary involvement, the immune endocrine response may promote an unfavorable environment. Chronic infectious diseases, and their persistent proinflammatory response, may affect mucosal barriers integrity favoring the translocation of gastrointestinal bacteria, leading to an increase of circulating lipopolysaccharides (LPS). Consequently, we quantified LPS levels in TB patients, with different degrees of pulmonary involvement, and controls (Co) and analyzed the possible relationship between LPS and inflammatory mediators i.e., C reactive protein (CRP), interleukin 6 (IL-6) and Interferon-gamma (IFN-γ), Erythrocyte Sedimentation Rate (ESR), steroid hormones (Cortisol and Dehydroepiandrosterone, DHEA), and inflammatory transcripts from peripheral blood mononuclear cells (IL-1ß, IL-6, IFN-γ). LPS was assessed by the Limulus amoebocyte lysate assay and the ELISA technique was used to quantify hormones and cytokines in the plasma samples. Cytokine transcripts from PBMC were evaluated by qRT-PCR. Non-parametric tests were used. LPS levels were increased in TB patients, as did levels of CRP, IL-6, IFN-γ, cortisol and ESR. Severe patients had the highest amounts of circulating LPS; with moderate and severe cases showing much higher levels of CRP, ESR, IL-6, IFN-γ and cortisol/DHEA ratio, as an endocrine imbalance. Only in PBMC from severe cases was mRNA for IL-1ß increased. Correlation analysis showed that levels of LPS from severe patients were positively associated with IL-6 and IFN-γ plasma concentrations and with IL-1ß transcripts, while IL-6 had a positive correlation with the cortisol/DHEA ratio. The higher levels of circulating LPS during progressive TB may emerge as a contributing factor for the persistence of the greater immune endocrine imbalance distinctive of advanced disease, which might suggest a vicious cycle among LPS, inflammation and endocrine imbalance.


Assuntos
Lipopolissacarídeos/sangue , Tuberculose/sangue , Adolescente , Adulto , Idoso , Proteína C-Reativa/metabolismo , Humanos , Interferon gama/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Leucócitos Mononucleares/metabolismo , Pessoa de Meia-Idade , Mycobacterium tuberculosis/metabolismo , Adulto Jovem
6.
Medicine (Baltimore) ; 100(31): e26757, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397819

RESUMO

ABSTRACT: The role of cognitive, social and biological factors in the etiology of chronic periodontitis has been reported.The aim of this study was to evaluate the salivary cortisol level and interleukin-1 B level in patients of Chronic periodontitis in smokers and stress and nonsmokers without stress.The design of study randomized, prospective, double-blinded, and prospective study.The total sample size was comprised of 600 subjects between the ages of 20 and 50 years. The sample size was divided into 300 males and 300 females. Out of 600 subjects, 200 subjects comprised of subjects with chronic periodontitis with positive depression level with a history of smoking (Group I), 200 subjects comprised of subjects with chronic periodontitis without depression and without smoking (Group II), and 200 subjects who were taken as the control group comprised of healthy subjects without chronic periodontitis, without depression level, and no smoking history (Group III). Salivary cortisol levels were determined by enzyme-linked immunosorbent assay (ELISA).The result showed that there was a positive correlation between morning and evening salivary cortisol level in all the groups with correlation coefficient. There was significant higher value of salivary cortisol in Group I patients when compared with Group II and Group III. However, when the comparison of salivary cortisol levels was done between the Group II and Control group, the result showed nonsignificant P value.It is suggested that stress is positively correlated with the salivary cortisol levels in smokers and nonsmokers.


Assuntos
Periodontite Crônica/sangue , Hidrocortisona/análise , Interleucina-1beta/análise , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Periodontite Crônica/diagnóstico , Periodontite Crônica/epidemiologia , Feminino , Voluntários Saudáveis , Humanos , Hidrocortisona/sangue , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Saliva/enzimologia , Fumar/efeitos adversos , Fumar/epidemiologia , Fumar/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia
7.
Sci Rep ; 11(1): 17227, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446770

RESUMO

Cattle vary in their susceptibility to infection and immunopathology, but our ability to measure and longitudinally profile immune response variation is limited by the lack of standardized immune phenotyping assays for high-throughput analysis. Here we report longitudinal innate immune response profiles in cattle using a low-blood volume, whole blood stimulation system-the ImmunoChek (IChek) assay. By minimizing cell manipulation, our standardized system minimizes the potential for artefactual results and enables repeatable temporal comparative analysis in cattle. IChek successfully captured biological variation in innate cytokine (IL-1ß and IL-6) and chemokine (IL-8) responses to 24-hr stimulation with either Gram-negative (LPS), Gram-positive (PamCSK4) bacterial or viral (R848) pathogen-associated molecular patterns (PAMPs) across a 4-month time window. Significant and repeatable patterns of inter-individual variation in cytokine and chemokine responses, as well as consistent high innate immune responder individuals were identified at both baseline and induced levels. Correlation coefficients between immune response read-outs (IL-1ß, IL-6 and IL-8) varied according to PAMP. Strong significant positive correlations were observed between circulating monocytes and IL-6 levels for null and induced responses (0.49-0.61) and between neutrophils and cytokine responses to R848 (0.38-0.47). The standardized assay facilitates high-throughput bovine innate immune response profiling to identify phenotypes associated with disease susceptibility and responses to vaccination.


Assuntos
Bovinos/imunologia , Imunidade Inata/imunologia , Testes Imunológicos/métodos , Padrões Moleculares Associados a Patógenos/imunologia , Imunidade Adaptativa/imunologia , Animais , Bovinos/sangue , Ensaio de Imunoadsorção Enzimática , Imidazóis/imunologia , Interleucina-1beta/sangue , Interleucina-1beta/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Interleucina-8/sangue , Interleucina-8/imunologia , Lipopolissacarídeos/imunologia , Neutrófilos/imunologia , Padrões Moleculares Associados a Patógenos/sangue , Fatores de Tempo
8.
J Clin Invest ; 131(20)2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34464357

RESUMO

BACKGROUNDMultisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Kawasaki disease (KD) shares several clinical features with MIS-C, which prompted the use of intravenous immunoglobulin (IVIG), a mainstay therapy for KD. Both diseases share a robust activation of the innate immune system, including the IL-1 signaling pathway, and IL-1 blockade has been used for the treatment of both MIS-C and KD. The mechanism of action of IVIG in these 2 diseases and the cellular source of IL-1ß have not been defined.METHODSThe effects of IVIG on peripheral blood leukocyte populations from patients with MIS-C and KD were examined using flow cytometry and mass cytometry (CyTOF) and live-cell imaging.RESULTSCirculating neutrophils were highly activated in patients with KD and MIS-C and were a major source of IL-1ß. Following IVIG treatment, activated IL-1ß+ neutrophils were reduced in the circulation. In vitro, IVIG was a potent activator of neutrophil cell death via PI3K and NADPH oxidase, but independently of caspase activation.CONCLUSIONSActivated neutrophils expressing IL-1ß can be targeted by IVIG, supporting its use in both KD and MIS-C to ameliorate inflammation.FUNDINGPatient Centered Outcomes Research Institute; NIH; American Asthma Foundation; American Heart Association; Novo Nordisk Foundation; NIGMS; American Academy of Allergy, Asthma and Immunology Foundation.


Assuntos
COVID-19/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/terapia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/terapia , COVID-19/sangue , COVID-19/imunologia , COVID-19/terapia , Estudos de Casos e Controles , Morte Celular/imunologia , Linhagem da Célula/imunologia , Criança , Pré-Escolar , Proteína Ligante Fas/imunologia , Feminino , Humanos , Lactente , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/sangue , Contagem de Leucócitos , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Ativação de Neutrófilo , Neutrófilos/classificação , Neutrófilos/imunologia , Neutrófilos/patologia , Síndrome de Resposta Inflamatória Sistêmica/sangue
9.
Cells ; 10(8)2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34440853

RESUMO

Insulin receptor substrate (IRS) 2 is a key mediator of insulin signaling and IRS-2 knockout (IRS2-/-) mice are a preclinical model to study the development of diabetes, as they develop peripheral insulin resistance and beta-cell failure. The differential inflammatory profile and insulin signaling in the hypothalamus of non-diabetic (ND) and diabetic (D) IRS2-/- mice might be implicated in the onset of diabetes. Because the lipid profile is related to changes in inflammation and insulin sensitivity, we analyzed whether ND IRS2-/- mice presented a different hypothalamic fatty acid metabolism and lipid pattern than D IRS2-/- mice and the relationship with inflammation and markers of insulin sensitivity. ND IRS2-/- mice showed elevated hypothalamic anti-inflammatory cytokines, while D IRS2-/- mice displayed a proinflammatory profile. The increased activity of enzymes related to the pentose-phosphate route and lipid anabolism and elevated polyunsaturated fatty acid levels were found in the hypothalamus of ND IRS2-/- mice. Conversely, D IRS2-/- mice have no changes in fatty acid composition, but hypothalamic energy balance and markers related to anti-inflammatory and insulin-sensitizing properties were reduced. The data suggest that the concurrence of an anti-inflammatory profile, increased insulin sensitivity and polyunsaturated fatty acids content in the hypothalamus may slow down or delay the onset of diabetes.


Assuntos
Citocinas/metabolismo , Hipotálamo/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Animais , Glicemia/metabolismo , Quimiocina CX3CL1/sangue , Citocinas/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Metabolismo Energético/genética , Ácidos Graxos Insaturados/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Proteínas Substratos do Receptor de Insulina/deficiência , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Leptina/metabolismo , Metabolismo dos Lipídeos/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
10.
Sci Rep ; 11(1): 15405, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321599

RESUMO

Cystic fibrosis (CF) is a multi-system disease that is characterized by lung disease due to recurrent airway infection and inflammation. Endocrine complications, such as CF bone disease (CFBD), are increasingly identified as patients are living longer. The cause of CFBD is multifactorial with chronic systemic inflammation theorized to be a contributing factor. Thus, we attempted to identify inflammatory biomarkers that are associated with CFBD. We conducted a retrospective observational study of 56 adult patients with CF with an average percentage predictive forced expiratory volume in one second (ppFEV1) of 73.7% (standard deviation: 30.0) who underwent baseline serum analysis for osteoprotegerin (OPG) and pro-inflammatory biomarkers (IL-1ß, IL-6, IL-8 and TNF-α), and had repeated dual-energy x-ray absorptiometry (DXA) scans separated by at least 2 years to examine correlations between serum biomarkers and bone mineral density (BMD) measurements. Univariate linear regression model analysis demonstrated that serum IL-1ß and IL-8, but not other pro-inflammatory markers, were negatively correlated with baseline BMD results. However, after accounting for confounding variables, only the relationship between IL-8 and left femoral neck BMD remained statistically significant. Additionally, IL-8 level was associated with BMD decline over time. These results suggest that IL-8 might play a unique role in the pathophysiology of CFBD relative to other pro-inflammatory cytokines but further study is warranted before firm conclusions can be made.


Assuntos
Densidade Óssea/genética , Fibrose Cística/sangue , Colo do Fêmur/metabolismo , Interleucina-1beta/sangue , Interleucina-8/sangue , Adolescente , Adulto , Remodelação Óssea/genética , Fibrose Cística/genética , Fibrose Cística/patologia , Colo do Fêmur/patologia , Humanos , Inflamação/sangue , Inflamação/genética , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/genética , Osteoporose/patologia , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
11.
Cancer Sci ; 112(10): 4050-4063, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34289209

RESUMO

Astragalus polysaccharides (APS), the main effective component of Astragalus membranaceus, can inhibit tumor growth, but the underlying mechanisms remain unclear. Previous studies have suggested that APS can regulate the gut microenvironment, including the gut microbiota and fecal metabolites. In this work, our results showed that APS could control tumor growth in melanoma-bearing mice. It could reduce the number of myeloid-derived suppressor cells (MDSC), as well as the expression of MDSC-related molecule Arg-1 and cytokines IL-10 and TGF-ß, so that CD8+ T cells could kill tumor cells more effectively. However, while APS were administered with an antibiotic cocktail (ABX), MDSC could not be reduced, and the growth rate of tumors was accelerated. Consistent with the changes in MDSC, the serum levels of IL-6 and IL-1ß were lowest in the APS group. Meanwhile, we found that fecal suspension from mice in the APS group could also reduce the number of MDSC in tumor tissues. These results revealed that APS regulated the immune function in tumor-bearing mice through remodeling the gut microbiota. Next, we focused on the results of 16S rRNA, which showed that APS significantly regulated most microorganisms, such as Bifidobacterium pseudolongum, Lactobacillus johnsonii and Lactobacillus. According to the Spearman analysis, the changes in abundance of these microorganisms were related to the increase of metabolites like glutamate and creatine, which could control tumor growth. The present study demonstrates that APS attenuate the immunosuppressive activity of MDSC in melanoma-bearing mice by remodeling the gut microbiota and fecal metabolites. Our findings reveal the therapeutic potential of APS to control tumor growth.


Assuntos
Astrágalo (Planta)/química , Linfócitos T CD8-Positivos/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Melanoma/tratamento farmacológico , Células Supressoras Mieloides/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Antibacterianos/administração & dosagem , Arginase/efeitos dos fármacos , Arginase/metabolismo , Bifidobacterium/efeitos dos fármacos , Bifidobacterium/metabolismo , Combinação de Medicamentos , Transplante de Microbiota Fecal , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Tolerância Imunológica , Interleucina-10/metabolismo , Interleucina-1beta/sangue , Interleucina-6/sangue , Lactobacillus/efeitos dos fármacos , Masculino , Melanoma/imunologia , Melanoma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , RNA Ribossômico 16S/análise , Fator de Crescimento Transformador beta/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral/imunologia
12.
Arterioscler Thromb Vasc Biol ; 41(9): 2509-2511, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34261329
13.
Sci Rep ; 11(1): 14752, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285283

RESUMO

The present investigation using Positron Emission Tomography shows how peptide VSAK can reduce the detrimental effects produced by lipopolysaccharides in Dutch dwarf rabbits, used to develop the Systemic Inflammatory Response Syndrome (SIRS). Animals concomitantly treated with lipopolysaccharides (LPS) and peptide VSAK show important protection in the loss of radiolabeled-glucose uptake observed in diverse organs when animals are exclusively treated with LPS. Treatment with peptide VSAK prevented the onset of changes in serum levels of glucose and insulin associated with the establishment of SIRS and the insulin resistance-like syndrome. Treatment with peptide VSAK also allowed an important attenuation in the circulating levels of pro-inflammatory molecules in LPS-treated animals. As a whole, our data suggest that peptide VSAK might be considered as a candidate in the development of new therapeutic possibilities focused on mitigating the harmful effects produced by lipopolysaccharides during the course of SIRS.


Assuntos
Glucose/metabolismo , Lipopolissacarídeos/administração & dosagem , Peptídeos/administração & dosagem , Tomografia por Emissão de Pósitrons , Síndrome de Resposta Inflamatória Sistêmica/patologia , Sequência de Aminoácidos , Animais , Modelos Animais de Doenças , Fluordesoxiglucose F18/química , Glucose/análise , Insulina/sangue , Interleucina-1beta/sangue , Rim/diagnóstico por imagem , Rim/metabolismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Lipopolissacarídeos/metabolismo , Fígado/diagnóstico por imagem , Fígado/metabolismo , Masculino , Simulação de Dinâmica Molecular , Peptídeos/química , Peptídeos/metabolismo , Coelhos , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Fator de Necrose Tumoral alfa/sangue
14.
Vet Immunol Immunopathol ; 237: 110274, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34091257

RESUMO

Commercially available bovine-specific assays are limited in number, and multiplex assays for this species are rare. Our objective was to develop a multiplex assay for the bovine inflammatory cytokines IL-1ß, IL-6, and TNF-α using the Meso Scale Discovery U-PLEX platform. "Do-It-Yourself" ELISA kits that contained polyclonal antibodies, both unlabeled and biotinylated, and the specific recombinant bovine cytokine standard, were purchased for each of these three cytokines. The biotinylated antibodies were coupled to linkers that bind to specific locations within each well of the U-PLEX plate. Unique linkers were used for each of the cytokines. The unlabeled antibodies were conjugated with electrochemiluminescent labels to serve as detection antibodies. Each cytokine assay was optimized individually prior to performing an optimization on the multiplex assay containing reagents for all three cytokines. To calculate cytokine concentrations, standard curves were developed using the recombinant cytokines and were run concurrently on each plate. Standard curves for IL-1ß and TNF-α were run at concentrations ranging from 0 to 50,000 pg/mL, and for IL-6 from 0 to 10,000 pg/mL. The average lowest level of detection concentration measured by the standard curves were 5.3 pg/mL, 0.92 pg/mL, and 22.34 pg/mL for IL-1ß, IL-6, and TNF-α respectively, as determined by data from seven plates containing bovine plasma samples from a combination of healthy and diseased cattle. The U-PLEX platform was a viable means to develop custom analyte- and species-specific multiplex assays using privately developed or purchased sets of commercially available reagents.


Assuntos
Bovinos/sangue , Ensaio de Imunoadsorção Enzimática/veterinária , Interleucina-1beta/sangue , Fator de Necrose Tumoral alfa/sangue , Animais , Complexo Respiratório Bovino/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Interleucina-6/sangue , Estudos Longitudinais , Sensibilidade e Especificidade
15.
J Int Soc Sports Nutr ; 18(1): 42, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090451

RESUMO

OBJECTIVE: Systemic elevations in pro-inflammatory cytokines are a marker of non-functional over reaching, and betaine has been shown to reduce the secretion of pro-inflammatory cytokines in vitro. The aim of this study was to investigate the effects of betaine supplementation on tumor necrosis factor alpha (TNF-α), interleukins-1 beta (IL-1ß), - 6 (IL-6) and the complete blood cell (CBC) count in professional youth soccer players during a competitive season. METHODS: Twenty-nine soccer players (age, 15.5 ± 0.3 years) were randomly divided into two groups based on playing position: betaine group (BG, n = 14, 2 g/day) or placebo group (PG, n = 15). During the 14-week period, training load was matched and well-being indicators were monitored daily. The aforementioned cytokines and CBC were assessed at pre- (P1), mid- (P2), and post- (P3) season. RESULTS: Significant (p < 0.05) group x time interactions were found for TNF-α, IL-1ß, and IL-6. These variables were lower in the BG at P2 and P3 compared to P1, while IL-1ß was greater in the PG at P3 compared to P1 (p = 0.033). The CBC count analysis showed there was significant group by time interactions for white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and mean corpuscular hemoglobin concentration (MCHC). WBC demonstrated increases at P3 compared to P2 in PG (p = 0.034); RBC was less at P3 compared to P1 in BG (p = 0.020); Hb was greater at P2 compared to P1, whilst it was less at P3 compared to P3 for both groups. MCHC was greater at P3 and P2 compared to P1 in BG, whereas MCHC was significantly lower at P3 compared to P2 in the PG (p = 0.003). CONCLUSION: The results confirmed that 14 weeks of betaine supplementation prevented an increase in pro-inflammatory cytokines and WBC counts. It seems that betaine supplementation may be a useful nutritional strategy to regulate the immune response during a fatiguing soccer season.


Assuntos
Betaína/administração & dosagem , Comportamento Competitivo/fisiologia , Citocinas/sangue , Suplementos Nutricionais , Futebol/fisiologia , Adolescente , Biomarcadores/sangue , Contagem de Células Sanguíneas , Método Duplo-Cego , Índices de Eritrócitos , Hemoglobinometria , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue
16.
Ecotoxicol Environ Saf ; 221: 112448, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34174739

RESUMO

Atmospheric PM2.5 can induce airway inflammation and mucin secretion. MUC5B is required for airway defense. However, the research on the role of MUC5B in airway inflammation induced by atmospheric PM2.5 remains limited. This study was designed to explore the role of MUC5B in airway inflammation induced by atmospheric PM2.5. In vivo, Wistar rats were exposed to 0, 1.5, 7.5, 37.5 mg/ kg PM2.5 saline suspension via intratracheal instillation. HE staining and AB-PAS staining were used to observe the airway inflammation and goblet cell hyperplasia. In vitro, normal A549 cells and MUC5B-knockdown A549 cells were exposed to 0, 100, 200 and 400 µg/mL PM2.5 for 6 h, 12 h, 24 h and 48 h. ELISA was used to measure the levels of TNF-α and IL-1ß in serum and bronchoalveolar lavage fluid of rats and in cell culture. Real time-PCR and ELISA were used to quantify the mRNA and protein levels of MUC5B in trachea and lung of rats and in A549 cells. PM2.5 could cause the infiltration of inflammatory cells and increase the mucus secretions and goblet cell metaplasia. MUC5B is related to rats' airway inflammation induced by PM2.5. A549 cells exposed to PM2.5 in higher concentration and longer time, the protein level of MUC5B was significantly increased, while the levels of IL-1ß, TNF-α and MUC5B mRNA were significantly decreased. Compared with normal A549 cells, the levels of IL-1ß and TNF-α were significantly higher in Muc5b-knockdown cells. Atmospheric PM2.5 can induce airway inflammation and mucin secretion. MUC5B played a critical role in controlling the inflammatory response induced by PM2.5.


Assuntos
Inflamação/metabolismo , Mucina-5B/metabolismo , Material Particulado/toxicidade , Células A549 , Animais , Líquido da Lavagem Broncoalveolar/química , Feminino , Humanos , Interleucina-1beta/sangue , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Pulmão/metabolismo , Masculino , Mucina-5B/genética , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
17.
Sci Rep ; 11(1): 11903, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099791

RESUMO

Systemic juvenile idiopathic arthritis (sJIA) and cryopyrin-associated periodic syndrome (CAPS) share many common manifestations. We aim to identify an applicable method to assist disease discrimination. Inflammatory cytokines were measured in the plasma of patients with CAPS, sJIA with persistent disease course and healthy controls. Supernatants collected from non-stimulated peripheral blood mononuclear cells (PBMCs) and those undergone inflammasome stimulation tests utilizing lipopolysaccharide (LPS) with and without adenosine triphosphate (ATP) were investigated. Inflammatory cytokines in patient plasma fail to differentiate sJIA from CAPS. PBMCs from sJIA secrets higher amount of IL-1ß and IL-18 while CAPS PBMCs produces more caspase-1 without stimulation. IL-1ß, IL-18, and caspase-1 were significantly elevated among CAPS PBMCs (all p < 0.05) upon LPS stimulation, but not when additional ATPs were provided. Levels of cytokines and PBMC responses to the stimulation assays were similar among all sJIA patients regardless of their history of macrophage activation syndrome. Unstimulated PBMC activities and the LPS inflammasome stimulation assay without exogenic ATPs can assist the differentiation of CAPS from sJIA with persistent disease course.


Assuntos
Artrite Juvenil/diagnóstico , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Citocinas/sangue , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Adulto , Artrite Juvenil/sangue , Artrite Juvenil/metabolismo , Caspase 1/sangue , Células Cultivadas , Criança , Síndromes Periódicas Associadas à Criopirina/sangue , Síndromes Periódicas Associadas à Criopirina/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Interleucina-18/sangue , Interleucina-1beta/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Sensibilidade e Especificidade
18.
PLoS One ; 16(6): e0253470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34161370

RESUMO

Hepatitis C is considered a major public health problem caused by the hepatitis C virus (HCV). Viral infections are known to induce production of IL1ß through the signaling pathway of inflammasomes. Emerging evidences suggest that Inflammasome genes may influence the immune response against HCV as the host genetic background may contribute to the balance between acute and chronic inflammation. We investigated in 151 patients with chronic hepatitis C and 206 healthy blood donors' individuals (HD). Polymorphisms in the IL1B and IL18 genes were genotyped by PCR-RFLP, while NLRP3, CARD8, CTSB and AIM2 by RT- PCR. Serum assay of IL-1ß cytokine was performed by ELISA. 84 patients presented mild fibrosis (

Assuntos
Predisposição Genética para Doença , Hepatite C/genética , Inflamassomos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Brasil , Proteínas Adaptadoras de Sinalização CARD/genética , Catepsina B/genética , Proteínas de Ligação a DNA/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Interleucina-18/genética , Interleucina-1beta/sangue , Interleucina-1beta/genética , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas de Neoplasias/genética , Adulto Jovem
19.
Front Immunol ; 12: 637845, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995355

RESUMO

Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects of reflex physiological sympathetic activation in endotoxemic rats using bilateral carotid occlusion (BCO), a physiological approach involving the baroreflex and chemoreflex mechanisms and the influence of the baroreceptors and peripheral chemoreceptors in the cardiovascular and systemic inflammatory responses. After lipopolysaccharide (LPS) administration, the arterial pressure was recorded during 360 min in unanesthetized rats, and serial blood samples were collected to analyze the plasma cytokine levels. BCO elicited the reflex activation of the sympathetic nervous system, providing the following outcomes: (I) increased the power of the low-frequency band in the spectrum of the systolic arterial pressure during the BCO period; (II) reduced the levels of pro-inflammatory cytokines in plasma, including the tumor necrosis factor (TNF) and the interleukin (IL)-1ß; (III) increased the plasma levels of anti-inflammatory cytokine IL-10, 90 min after LPS administration. Moreover, selective baroreceptor or chemoreceptor denervation deactivated mechanosensitive and chemical sensors, respectively, and decreased the release of the LPS-induced cytokine but did not alter the BCO modulatory effects. These results show, for the first time, that physiological reflex activation of the sympathetic circuit decreases the inflammatory response in endotoxemic rats and suggest a novel function for the baroreceptors as immunosensors during the systemic inflammation.


Assuntos
Barorreflexo/fisiologia , Endotoxemia/patologia , Inflamação/fisiopatologia , Pressorreceptores/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Sistema Nervoso Autônomo/fisiologia , Pressão Sanguínea/fisiologia , Células Quimiorreceptoras/fisiologia , Interleucina-10/sangue , Interleucina-1beta/sangue , Lipopolissacarídeos , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
20.
Front Immunol ; 12: 668113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936110

RESUMO

Background: People living with HIV (PLWH) have increased systemic inflammation, and inflammation has been suggested to contribute to the pathogenesis of emphysema. We investigated whether elevated cytokine concentrations (interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), soluble CD14 (sCD14) and sCD163 were independently associated with radiographic emphysema in PLWH. Methods: We included PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study without hepatitis B and C co-infection and with a plasma sample and a chest computed tomography scan available. Emphysema plus trace emphysema was defined as the percentage of low attenuation area under -950 Houndsfield Unit (%LAA-950) using a cut-off at 5%. Cytokine concentrations were measured by ELISA or Luminex immunoassays. An elevated cytokine concentration was defined as above the 75th percentile. Results: Of 783 PLWH, 147 (18.8%) had emphysema. PLWH were predominantly male (86.0%) and 743 (94.9%) had undetectable viral replication. PLWH with emphysema had higher concentrations of TNFα (median (IQR): 8.2 (6.4-9.8) versus 7.1 (5.7-8.6) pg/ml, p<0.001), IL-1ß (0.21 (0.1-0.4) versus 0.17 (0.1-0.3) pg/ml, p=0.004) and IL-6 (3.6 (2.6-4.9) versus 3.1 (2.0-4.3) pg/ml, p=0.023) than PLWH without. In a logistic regression model adjusted for age, sex, ethnicity, smoking status, BMI and CD4 nadir, elevated TNFα (adjusted odds ratio (aOR): 1.78 [95%CI: 1.14-2.76], p=0.011) and IL-1ß (aOR: 1.81 [95%CI: 1.16-2.81], p=0.009) were independently associated with emphysema. The association between IL-1ß and emphysema was modified by smoking (p-interaction=0.020) with a more pronounced association in never-smokers (aOR: 4.53 [95%CI: 2.05-9.98], p<0.001). Conclusion: Two markers of systemic inflammation, TNFα and IL-1ß, were independently associated with emphysema in PLWH and may contribute to the pathogenesis of emphysema. Importantly, the effect of IL-1ß seems to be mediated through pathways that are independent of excessive smoking. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02382822.


Assuntos
Infecções por HIV/sangue , Mediadores da Inflamação/sangue , Interleucina-1beta/sangue , Enfisema Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , Biomarcadores/sangue , Comorbidade , Estudos Transversais , Dinamarca/epidemiologia , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Enfisema Pulmonar/epidemiologia , Medição de Risco , Fatores de Risco , Regulação para Cima
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