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1.
Front Immunol ; 13: 884592, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072577

RESUMO

Background: Early identification of patients who will benefit from immune checkpoint inhibitors (ICIs) has recently become a hot issue in cancer immunotherapy. Peripheral cytokines are key regulators in the immune system that can induce the expression of immune checkpoint molecules; however, the association between peripheral cytokines and the efficiency of ICIs remains unclear. Methods: A systematic review was conducted in several public databases from inception through 3 February 2022 to identify studies investigating the association between peripheral cytokines (i.e., IL-1ß, IL-2, IL-2RA, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, IFN-γ, and TGF-ß) and ICI treatment. Survival data, including overall survival (OS) and/or progression-free survival (PFS), were extracted, and meta-analyses were performed. Results: Twenty-four studies were included in this analysis. The pooled results demonstrated that the pretreatment peripheral levels of IL-6 (univariate analysis: HR = 2.53, 95% CI = 2.21-2.89, p < 0.00001; multivariate analysis: HR = 2.21, 95% CI = 1.67-2.93, p < 0.00001) and IL-8 (univariate analysis: HR = 2.17, 95% CI = 1.98-2.38, p < 0.00001; multivariate analysis: HR = 1.88, 95% CI= 1.70-2.07, p < 0.00001) were significantly associated with worse OS of cancer patients receiving ICI treatment in both univariate and multivariate analysis. However, high heterogeneity was found for IL-6, which might be attributed to region, cancer type, treatment method, sample source, and detection method. Conclusion: The peripheral level of IL-8 may be used as a prognostic marker to identify patients with inferior response to ICIs. More high-quality prospective studies are warranted to assess the predictive value of peripheral cytokines for ICI treatment.


Assuntos
Citocinas , Inibidores de Checkpoint Imunológico , Neoplasias , Citocinas/sangue , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Interleucina-6/sangue , Interleucina-8/sangue , Neoplasias/tratamento farmacológico , Prognóstico
2.
Front Immunol ; 13: 901176, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059480

RESUMO

Objective: To identify less invasive and easily applicable serum cytokine-derived biomarkers which contribute to the diagnostic utility and risk assessment ability of the prostate health index (PHI) based multivariable model in grey zone aggressive prostate cancer (AG PCa) early detection. Methods: Serum 45 cytokines screening was performed in a small training cohort consisting of 10 sera by Luminex liquid array-based multiplexed immunoassays and identified TRAIL and IL-10 as new biomarkers for PHI diagnostic utility adjustment for further validation with a multivariable predictive model in a cohort including 79 aggressive prostate cancer patients and 209 benign prostatic hyperplasia or indolent PCa patients within the PSA grey zone. Results: TRAIL and IL-10 were identified as potential serum biomarkers for AG PCa detection by the result of multi-cytokines screening in the univariate analysis, while multivariable logistic regression confirmed the AUC of the full risk predictive model (0.915) including tPSA, fPSA, PHI, TRAIL, and IL-10 was higher than various diagnostic strategies. DCA suggested a superior net benefit and indicated a good discriminative ability of the full risk model consistently with the result of the nomogram. Conclusion: We suggest a significant advantage for the PHI-based multivariate combinations of serum TRAIL and IL-10 comparing to PHI or other serum-derived biomarkers alone in the detection and risk stratification of grey zone AG PCa.


Assuntos
Interleucina-10 , Próstata , Neoplasias da Próstata , Ligante Indutor de Apoptose Relacionado a TNF , Biomarcadores Tumorais/sangue , Citocinas/sangue , Detecção Precoce de Câncer , Humanos , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-10/metabolismo , Masculino , Próstata/metabolismo , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
3.
Front Immunol ; 13: 957361, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35983033

RESUMO

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs). The correlations between serum cytokine levels and clinical information in GFAP-A patients were analyzed. A total of 147 serological proteins were differentially expressed in GFAP-A patients compared to HCs, and 33 of these proteins were not observed in NMOSD patients. Serum levels of EG-VEGF negatively correlated with GFAP antibody titers, MIP-3 alpha positively correlated with clinical severity in GFAP-A patients, and LIGHT positively correlated with WBC counts and protein levels in the CSF of GFAP-A patients. These results suggest that GFAP and AQP4 astrocytopathy share some common pathology related to TNF signaling. Serum MIP 3 alpha may be a biomarker to assess clinical severity and a potential target for therapy of autoimmune GFAP astrocytopathy.


Assuntos
Astrócitos , Doenças Autoimunes , Citocinas , Encefalomielite , Astrócitos/patologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/patologia , Biomarcadores/sangue , Citocinas/sangue , Encefalomielite/diagnóstico , Encefalomielite/patologia , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Filamentos Intermediários
4.
Proc Natl Acad Sci U S A ; 119(34): e2117089119, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35943976

RESUMO

The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the "new normal." The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Convalescença , Citocinas , Dipeptídeos , Inibidores da Dipeptidil Peptidase IV , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Formação de Anticorpos , COVID-19/sangue , COVID-19/tratamento farmacológico , COVID-19/imunologia , Citocinas/sangue , Dipeptídeos/sangue , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Humanos , Aprendizado de Máquina , Metaboloma , Camundongos , SARS-CoV-2 , Vacinação
5.
Cytokine ; 158: 156006, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36044827

RESUMO

BACKGROUND: Sepsis is a global health challenge associated with significant morbidity and mortality. Detrimental sepsis effects are attributed to excessive inflammation or a "cytokine storm." However, anti-inflammation therapies have failed to lower sepsis mortality. We aim to characterize levels of key inflammatory cytokines in patients with sepsis and compare levels with those in healthy individuals and relate tumor necrosis factor (TNF) α levels to patient characteristics and outcomes. METHODS: We performed a systematic review and meta-analysis. Medline, Embase, Cochrane Library, and Web of Science Core Collection databases were searched between 1985 and May 2020. Analysis was restricted to studies in English. We included randomized controlled trials (RCTs), controlled trials, cohort studies, case series, and cross-sectional studies that reported mean levels of cytokines in the circulation thought to be relevant for sepsis pathogenesis. We also evaluated concentrations of these cytokines in healthy individuals. The Quality in Prognosis Studies tool was used to assess the methodological quality of included studies. We extracted summary data from published reports. Data analyses were performed using a random-effects model to estimate pooled odds ratios (OR) with 95% confidence intervals for cytokine levels and mortality. This systematic review is registered in PROSPERO (CRD42020179800). FINDINGS: We identified 3654 records, and 104 studies were included with a total of 3250 participants. The pooled estimated mean TNFα concentration in sepsis patients was 58.4 pg/ml (95% Confidence Interval or CI 39.8-85.8 pg/ml), and in healthy individuals was 5.5 pg/ml (95% CI 3.8-8.0 pg/ml). Pooled estimate means for IL-1ß and IFN-γ in sepsis patients were 21.8 pg/ml and 63.3 pg/ml, respectively. Elevated TNFα concentrations associated with increased 28-day sepsis mortality (p = 0.001). In subgroup analyses, we did not detect an association between TNFα levels and sepsis source, sepsis severity, or sequential organ failure assessment (SOFA) score. A TNF-α cutoff level ≥14.7 pg/ml separated sepsis patients from healthy individuals with a sensitivity of 82.6%, a specificity of 91.7%, and a likelihood ratio of 9.9. INTERPRETATION: Sepsis mean TNFα concentration is increased approximately 10-fold compared to mean concentration in healthy individuals, and TNFα associated with sepsis mortality but not sepsis severity. The concept that elevated cytokines cause sepsis should be revisited in the context of these data. FUNDING: None.


Assuntos
Citocinas , Sepse , Fator de Necrose Tumoral alfa , Citocinas/sangue , Voluntários Saudáveis , Humanos , Inflamação , Prognóstico , Sepse/complicações , Sepse/diagnóstico , Sepse/metabolismo , Fator de Necrose Tumoral alfa/sangue
6.
Proc Natl Acad Sci U S A ; 119(30): e2203659119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35858456

RESUMO

This study analyzed whole blood samples (n = 56) retrieved from 30 patients at 1 to 21 (median 9) mo after verified COVID-19 to determine the polarity and duration of antigen-specific T cell reactivity against severe acute respiratory syndrome coronavirus 2-derived antigens. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until ∼70 d after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-γ remained stable and highly correlated at 3 to 21 mo after infection. Similar cytokine dynamics were observed in unvaccinated, convalescent patients using whole-blood samples stimulated with peptides spanning the N-terminal portion of the spike 1 protein. These results unravel two phases of T cell reactivity following natural COVID-19: an early, synchronous response indicating transient presence of multipolar, antigen-specific T helper (TH) cells followed by an equally synchronous and durable TH1-like reactivity reflecting long-lasting T cell memory.


Assuntos
COVID-19 , Citocinas , SARS-CoV-2 , Linfócitos T Auxiliares-Indutores , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , COVID-19/sangue , COVID-19/imunologia , Convalescença , Citocinas/sangue , Humanos , Interferon gama/sangue , Proteínas do Nucleocapsídeo/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T Auxiliares-Indutores/imunologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-35805808

RESUMO

Multiple sclerosis (MS) is one of the most prevalent causes of nontraumatic neurological impairment in young adults. This review aims to determine the impact of exercise on cytokine and adipokine profile levels as inflammatory markers in MS patients across various exercise paradigms. We used specific keywords in PubMed, Web of Science, The Cochrane Library, and Scopus to find randomized clinical trials addressing the effects of physical activity and exercise training on inflammatory markers levels in MS patients. The majority of the research showed no considerable changes in IL-6 levels, while three studies reported declining levels after the intervention. Approximately half of the trials observed a change in TNF-α and IL-10 levels after exercise interventions, while the other half showed no meaningful changes. Other markers such as IL-17, IL-4, IL-12, adipokines, and BDNF showed fluctuations in levels. We found no universal agreement on the effects of different exercise training protocols on the serum level of inflammatory markers in patients with MS. More research is needed to fully identify the effects of exercise on cytokines in MS patients.


Assuntos
Adipocinas , Citocinas , Exercício Físico , Esclerose Múltipla , Adipocinas/sangue , Biomarcadores/sangue , Citocinas/sangue , Humanos , Esclerose Múltipla/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
8.
Front Immunol ; 13: 886144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865545

RESUMO

Background: Inflammation plays a pivotal role in the pathogenesis of cancer. Though previous studies have reported a link between several inflammatory biomarkers and risk of certain types of cancer, there is a lack of systematic investigation. Therefore, we aimed to assess the role of circulating cytokines on the risk of cancer using a two-sample Mendelian randomization (MR) approach. Method: We used genetic variants associated with circulating levels of cytokines from a meta-analysis of genome-wide association studies (GWASs) of 8,293 Finns as instrumental variables. Summary level data of 20 site-specific cancer were obtained from the UK BioBank including up to 456,348 participants of European ancestry. We performed two-sample MR analyses using inverse-variance weighted (IVW) method as the main method, followed by weighted-median and likelihood-based methods as sensitivity analysis. Pleiotropic and outlier variants were assessed by MR-Egger regression and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. Results: 224 genetic variants associated with 27 circulating cytokines achieving genome-wide significance (P<5×10-8) were used as IVs. After Bonferroni correction, genetically predicted high levels of interleukin-18 (IL-18) were associated with a decreased risk of acute myeloid leukemia (odds ratio (OR) per 1 standard deviation (SD) increase = 0.55, 95% confidence interval (CI):0.43-0.69, P=5.39×10-7), and circulating levels of IL-17 were associated with altered stomach cancer risk (OR per 1 SD increase = 0.15, 95% CI: 0.07-0.36, P=1.25×10-5) by IVW. Results were stable across sensitivity analyses, and MR-Egger regression did not suggest the presence of directional pleiotropy. Additionally, we found suggestive evidence for 48 cytokine-cancer associations including tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and cutaneous T-cell attracting chemokine (CTACK) with the risk of several types of cancer (9.26×10-5≤P<0.05). Conclusions: By using a genetic epidemiological approach, our study systematically evaluated the role of circulating cytokines on the risk of cancer, and provided clues for potential therapeutic targets. However, the exact underlying biological mechanism warrants further investigation.


Assuntos
Citocinas , Neoplasias , Citocinas/sangue , Estudo de Associação Genômica Ampla , Humanos , Funções Verossimilhança , Neoplasias/epidemiologia , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco
9.
Front Immunol ; 13: 930582, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844528

RESUMO

Pregnancy-induced hypertension (PIH) is one of the most common pregnancy complications that seriously affects the mother and fetus. The incidence of PIH is higher in pregnancies conceived after assisted reproductive technology (ART) than in spontaneous pregnancies; thus, exploring potential serum biomarkers before PIH onset is of great significance for effective early prediction and prevention of PIH in the ART population. Cytokines are involved in the inflammatory response and immune regulation, which play an essential role in the pathogenesis of PIH. A description of the cytokine profile in the first trimester of pregnancy could help identify new diagnostic tools and develop targeted therapies for PIH in the ART population. The concentrations of classical predictive markers for PIH and another 48 cytokines were measured in the first-trimester pregnancy serum samples from 33 PIH patients and 33 matched normotensive controls (NC), both of whom conceived after ART treatment. The measured values were compared and analyzed between NC and PIH, followed by comprehensive bioinformatic analysis and logistic regression analysis. There was no significant difference in classical predictive markers, including Activin A, PlGF, sFLT1 (VEGFR), and sFLT1/PlGF, between the PIH and NC groups (P > 0.05), while 29 cytokines were significantly lower in the PIH group than in the NC group (P < 0.05). Logistic regression analysis revealed that 17 cytokines (IL-2Rα, M-CSF, IL-6, IL-2, ß-NGF, IL-7, IL-12 (p70), SCF, IL-10, IL-9, MIG, GM-CSF, LIF, IL-1α, MCP-3, IL-4, and HGF) in the first-trimester pregnancy serum were significantly negatively correlated with the subsequent onset of PIH. With the top 3 cytokines (IL-7, MIG, and SCF) of receiver operating characteristic (ROC) analysis, we constructed an efficient multifactor combined detection and prediction model for PIH in ART pregnancy. Classical early predictors for hypertensive disorder complicating pregnancy cannot distinguish PIH from their normal peers in ART pregnancy. In comparison, the description of the cytokine profile in the first trimester of pregnancy enables us to distinguish high-risk ART pregnancy for PIH, permitting enough time for PIH prevention therapy. The cytokine profile we described also provides immunological insight into the further mechanistic exploration of PIH.


Assuntos
Citocinas , Hipertensão Induzida pela Gravidez , Técnicas de Reprodução Assistida , Citocinas/sangue , Feminino , Humanos , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/diagnóstico , Gravidez
10.
J Physiol Pharmacol ; 73(1)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35793765

RESUMO

Progranulin and family with sequence similarity 19, member A5 (FAM19A5) protein are adipokines with growing importance in the context of metabolic diseases. The study aimed to determine the serum concentration of progranulin and FAM19A5 in people with metabolic syndrome (MS) compared to those without MS. The concentration of progranulin and FAM19A5 was determined in 45 people with MS (group A) and in 35 healthy people without MS (group B). Body composition analysis, blood pressure, blood oxygen saturation and anthropometric measurements were performed. There were no differences in the blood levels of progranulin and FAM19A5 between the groups. In group A, the level of progranulin was 29.25±36.92 pg/ml and in group B it was 46.00±60.12pg/ml (p=0.2693). The level of FAM19A5 was 163.16±55.11 pg/ml and 197.57±112.89 pg/ml (p=0.1341) in subjects with and without metabolic syndrome, respectively. In group A, there was a correlation between FAM19A5 and diastolic blood pressure (DBP) (R= -0.40) and high-density lipoprotein (HDL) level (R= -0.37). In group B, correlations were found between progranulin and waist circumference (R= -0.43) and progranulin and triglyceride (TG) levels (R= -0.42). Both groups together showed correlations between progranulin level and body mass index (R= -0.24), HDL (R=0.25) and TG levels (R= -0.25) and between FAM19A5 level and DBP (R= -0.34). In conclusion, patients with and without MS do not differ in the range of progranulin and FAM19A5 serum levels. In patients with MS, elevated FAM19A5 serum levels may be an indicator of dyslipidaemia development. FAM19A5 appears to be a better predictor of MS than progranulin.


Assuntos
Citocinas , Síndrome Metabólica , Progranulinas , Pressão Sanguínea , Índice de Massa Corporal , Citocinas/sangue , Humanos , Síndrome Metabólica/sangue , Progranulinas/sangue
11.
Mediators Inflamm ; 2022: 8245717, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795404

RESUMO

Background: Occupational exposure to wood dust particles has long been reported of its associated varying degrees of negative health effects due to different extractive chemicals present in the various timber species. However, tropical hardwood is also reported to have higher levels of extractive chemicals of antihistamine, antioxidant, and anti-inflammatory properties. In Ghana, woodworkers have for years been exposed to wood dust from mixed tropical hardwood species, with little or no protective equipment such as nose masks, yet with less significant respiratory conditions. This study seeks to investigate the serum cytokine profile in tropical hardwood workers in Kumasi to provide a better understanding of the immunoregulatory pattern activated in the woodworkers. Method: The study was carried out among woodworkers, teachers, and security men located in Kumasi. A cross-sectional sampling of adult male workers was selected to participate in the study (86 woodworkers and 89 nonwoodworkers). Participants donated blood collected by venepuncture into EDTA tubes and spun to separate serum for cytokine assay. Cytokines including IFN-gamma, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, and IL-17 were assayed using the Human Premixed Multianalyte Kit (R&D System, Inc., Minneapolis, USA) following the manufacturer's procedure. The cytokine levels were quantified using the Luminex∗200 analyser. Results: The mean concentration levels for the various cytokines were significantly different (p < 0.05) between woodworkers and nonwoodworkers except IL-2. There were significantly increased levels of Th1 and Th2 cytokines expressed in the woodworkers more than the nonwoodworkers. Conclusions: The results from this study reveal that exposed woodworkers of mixed tropical hardwood species show a high level of Th1 and Th2 cytokines in their serum than nonwoodworkers.


Assuntos
Citocinas , Doenças Profissionais , Exposição Ocupacional , Árvores , Madeira , Adulto , Estudos Transversais , Citocinas/sangue , Poeira , Humanos , Interleucina-2/sangue , Contagem de Leucócitos , Masculino , Doenças Profissionais/sangue , Exposição Ocupacional/análise
12.
Artigo em Chinês | MEDLINE | ID: mdl-35822356

RESUMO

Objective:To explore the diagnostic value of a novel test paper, which detect eosinophil cationic protein(ECP) of nasal secretion in allergic rhinitis(AR). Methods:Nasal secretion and serum samples from 107 patients with allergic rhinitis(AR group) and 40 healthy volunteers(control group) were selected. The nasal symptoms were also evaluated in AR group. The degree of ECP coloration was evaluated by nasal secretion eosinophil cationic protein-myeloperoxid(ECP-MPO) test paper, and the concentration of ECP in nasal secretion and the concentration of cytokines in serum were detected at the same time. The difference and correlation among these indexes were analyzed. The best cutoff value and test efficiency of ECP chromogenic grade and concentration of nasal secretion were calculated by receiver operating characteristic curve(ROC). Results:The concentration of ECP in nasal secretion of AR patients was significantly higher than that of healthy controls(P<0.05). The color grade of nasal secretion detected by the test paper was positively correlated with the concentration of ECP in nasal secretion(P<0.05), and there was significant difference among different grades(P<0.05). There was a satisfying symmetry between the ECP color grade of nasal secretion and the serum specific IgE(sIgE) level as well as a high diagnostic consistency between them(P<0.05). The area under the curve(AUC) of ECP concentration ROC in nasal secretion was 0.807 2, corresponding to 64% sensitivity and 85% specificity when the cutoff value was set at 0.980 5; when the cutoff value was set at 1, the AUC of nasal secretion ECP color grading was 0.941 9, corresponding to 92% sensitivity and 94% specificity. No clear correlation between the concentration of ECP in nasal secretion and serum cytokines was found(P>0.05). Conclusion:The results of this novel test paper is in good agreement with those of serological allergens. It could serve as a preliminary test to evaluate the severity of allergy with satisfactory sensitivity and specificity, and is especially suitable in clinical practice for primary hospital.


Assuntos
Proteína Catiônica de Eosinófilo , Fitas Reagentes , Rinite Alérgica , Estudos de Casos e Controles , Citocinas/sangue , Proteína Catiônica de Eosinófilo/análise , Humanos , Rinite Alérgica/sangue , Rinite Alérgica/diagnóstico , Sensibilidade e Especificidade
13.
Int J Rheum Dis ; 25(8): 844-850, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35694730

RESUMO

AIM: To evaluate the correlation of inflammatory cytokines with the treatment response to tumor necrosis factor inhibitor (TNFi) in axial spondyloarthritis (axSpA) patients. METHODS: This study enrolled 86 axSpA patients and 20 healthy controls (HCs). Inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-12, IL-17A, IL-21, IL-23, and IL-32 were determined in serum samples of axSpA patients before treatment and in HCs after enrollment. All patients received 40 mg adalimumab every 2 weeks for 12 weeks; meanwhile, ASAS40 (40 criteria of the Assessment by the SpondyloArthritis International Society) response rates were evaluated at weeks 2, 4, 8, and 12. RESULTS: Most inflammatory cytokines were elevated in axSpA patients compared with HCs (all P < 0.05) except for IL-32 (P = 0.101). In axSpA patients, ASAS40 response rates were 0%, 19.5%, 34.5%, 47.1%, and 56.3% at weeks 0, 2, 4, 8, and 12, respectively. Baseline [interquartile range] IL-6 (47.3 [32.5-53.4] pg/mL vs 31.7 [23.0-50.9] pg/mL, P = 0.005) and IL-17A (127.9 [90.7-149.5] pg/mL vs 96.6 [56.1-112.6] pg/mL, P < 0.001) were higher in axSpA patients with ASAS40 response compared with those without ASAS40 response, while baseline TNF-α, IL-1ß, IL-12, IL-21, IL-23, and IL-32 were not different between them (all P > 0.050). Multivariate logistic regression analysis disclosed that baseline IL-17A (P = 0.037), C-reactive protein (P = 0.012), and history of TNF inhibitor (P = 0.029) were independently associated with ASAS40 response. Furthermore, baseline IL-17A, C-reactive protein, history of TNFi, and their combination had an acceptable to good ability for predicting ASAS40 response. CONCLUSION: Measurement of pre-treatment inflammatory cytokine levels is valuable for predicting treatment efficacy of TNFi in axSpA patients.


Assuntos
Espondiloartrite Axial , Citocinas , Inibidores do Fator de Necrose Tumoral , Espondiloartrite Axial/tratamento farmacológico , Proteína C-Reativa , Citocinas/sangue , Humanos , Interleucina-12 , Interleucina-17 , Interleucina-23 , Interleucina-6 , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa
14.
J Cell Physiol ; 237(8): 3394-3407, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35754396

RESUMO

Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in coronavirus disease 2019 (COVID-19) patients. Mild and severe COVID-19 patients had lower extracellular adenosine triphosphate and adenosine levels, and higher cytokines than healthy controls. Mild COVID-19 patients presented lower frequencies of CD4+ CD25+ CD39+ (activated/memory regulatory T cell [mTreg]) and increased frequencies of high-differentiated (CD27- CD28- ) CD8+ T cells compared with healthy controls. Severe COVID-19 patients also showed higher frequencies of CD4+ CD39+ , CD4+ CD25- CD39+ (memory T effector cell), and high-differentiated CD8+ T cells (CD27- CD28- ), and diminished frequencies of CD4+ CD73+ , CD4+ CD25+ CD39+ mTreg cell, CD8+ CD73+ , and low-differentiated CD8+ T cells (CD27+ CD28+ ) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8+ T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4+ Annexin-V+ and CD8+ Annexin-V+ T cells, indicating increased T-cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4+ and CD8+ T cells of a healthy donor. Interestingly, the in vitro incubation of peripheral blood mononuclear cell from severe COVID-19 patients with adenosine reduced the nuclear factor-κB activation in T cells and monocytes. Together, these data add new knowledge to the COVID-19 immunopathology through purinergic regulation.


Assuntos
5'-Nucleotidase , Apirase , COVID-19 , Linfócitos T , 5'-Nucleotidase/metabolismo , Adenosina/sangue , Trifosfato de Adenosina/sangue , Anexinas , Apirase/metabolismo , Antígenos CD28/metabolismo , COVID-19/imunologia , Citocinas/sangue , Proteínas Ligadas por GPI/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Receptores Purinérgicos , Transdução de Sinais , Linfócitos T/imunologia
15.
Iran J Immunol ; 19(2): 184-192, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35767891

RESUMO

BACKGROUND: Concomitant signals from IL-6 and TGF-ß have a central role in the Th17 cells development and differentiation, and these cells are the main promoters of demyelinating inflammation in the central nervous system (CNS) resulting in multiple sclerosis (MS). OBJECTIVES: To evaluate the simultaneous IL-6 and TGF-ß gene and their receptor protein expression in patients with Relapsing-Remitting (RR)-MS. MATERIALS AND METHODS: IL-6 and TGF-ß mRNA and their receptor expression on the surface of CD4+T cells were evaluated using real-time PCR (RT-PCR) and flow cytometry, respectively. RESULTS: The IL-6 mRNA expression in patients with RRMS was significantly higher than in the controls (p= 0.019). When patients who did not receive any other treatment were compared with the controls, the significant difference was substantial (p=0.006). The TGF-ß mRNA expression in patients was lower than in the controls (p = 0.03). However, in patients receiving IFNß, it increased compared with the other patients (p= 0.036). There was no difference in cytokine receptor expression between patients and the control group. CONCLUSION: Our data conclude an increase and decrease in mRNA expression levels of IL-6 and TGF-ß in patients with RRMS, respectively. Moreover, there were no significant differences in receptor expression of either cytokines. Based on our data the balance of TGF and IL-6 appears to have a positive impact on the disease control.


Assuntos
Interferon beta , Interleucina-6 , Esclerose Múltipla Recidivante-Remitente , Fator de Crescimento Transformador beta , Citocinas/biossíntese , Citocinas/sangue , Citocinas/genética , Humanos , Interferon beta/genética , Interferon beta/farmacologia , Interleucina-6/análogos & derivados , Interleucina-6/biossíntese , Interleucina-6/sangue , Interleucina-6/genética , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta/biossíntese , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta/genética
16.
Dermatol Ther ; 35(8): e15616, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35668044

RESUMO

To evaluate the long-term clinical efficacy of apremilast in Behçet's disease (BD) and its effect on serum cytokine levels. This study included 15 BD patients who were treated with apremilast. The rates of change in oral and genital ulcers, skin lesions, arthritis, and arthralgia were evaluated every 3 months for 12 months. The efficacy of apremilast was compared between patients with and without oral ulcer remission. Changes in the serum levels of interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-10, IL-17A, IL-6, IL-8, and IL-23 between baseline and 3 months after apremilast initiation were compared. After 3 months, oral and genital ulcers disappeared in most cases. The skin and joint lesions tended to improve for up to 6 months; however, recurrence was observed after 9 months. The improvement of genital ulcers was earlier in the oral ulcer remission group than the oral ulcer non-remission group, with the genital ulcers disappearing within the first 3 months. The baseline levels of serum cytokines, analyzed in seven patients, did not exhibit significant associations with specific organ lesions. After administration of apremilast, the TNF-α and IL-23 levels significantly decreased; however, the IFN-γ, IL-6, IL-8, and IL-10 levels did not show significant changes. The rates of decrease in the serum IL-6, IFN-γ, and IL-10 levels were greater in patients with improved oral ulcers. Modulation of serum cytokine levels with apremilast might underlie the efficacy of apremilast in oral ulcers in BD patients.


Assuntos
Síndrome de Behçet , Citocinas , Úlceras Orais , Talidomida , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Citocinas/sangue , Humanos , Interferon gama , Interleucina-10 , Interleucina-23 , Interleucina-6 , Interleucina-8 , Úlceras Orais/diagnóstico , Úlceras Orais/tratamento farmacológico , Úlceras Orais/etiologia , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Fator de Necrose Tumoral alfa
17.
Front Immunol ; 13: 871780, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677047

RESUMO

Recent developments in multiplex technologies enable the determination of a large nu\mber of soluble proteins such as cytokines in various biological samples. More than a one-by-one determination of the concentration of immune mediators, they permit the establishment of secretion profiles for a more accurate description of conditions related to infectious diseases or vaccination. Cytokine profiling has recently been made available for bovine species with the development of a Luminex® technology-based 15-plex assay. Independently from the manufacturer, we evaluated the bovine cytokine/chemokine multiplex assay for limits of detection, recovery rate, and reproducibility. Furthermore, we assessed cytokine secretion in blood samples from 107 cows upon stimulation with heat-killed bacteria and TLR2/4 ligands compared to a null condition. Secretion patterns were analyzed either using the absolute concentration of cytokines or using their relative concentration with respect to the overall secretion level induced by each stimulus. Using Partial Least Square-Discriminant Analysis, we show that the 15-cytokine profile is different under Escherichia coli, Staphylococcus aureus, and Streptococcus uberis conditions, and that IFN-γ, IL-1ß, and TNF-α contribute the most to differentiate these conditions. LPS and E. coli induced largely overlapping biological responses, but S. aureus and S. uberis were associated with distinct cytokine profiles than their respective TLR ligands. Finally, results based on adjusted or absolute cytokine levels yielded similar discriminative power, but led to different stimuli-related signatures.


Assuntos
Bovinos , Citocinas , Receptores Toll-Like , Animais , Bovinos/sangue , Citocinas/sangue , Escherichia coli , Feminino , Ligantes , Reprodutibilidade dos Testes , Staphylococcus aureus , Streptococcus , Receptores Toll-Like/imunologia
18.
Int J Radiat Oncol Biol Phys ; 114(2): 266-274, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35675855

RESUMO

PURPOSE: The immunoinflammatory state has been shown to be associated with poor outcomes after radiation therapy (RT). We conducted an a priori designed validation study using serum specimens from Radiation Therapy Oncology Group (RTOG) 0521. It was hypothesized the pretreatment inflammatory state would correlate with clinical outcomes. METHODS AND MATERIALS: Patients on RTOG 0521 had serum banked for biomarker validation. This study was designed to validate previous findings showing an association between elevations in C-reactive protein (CRP) and shorter biochemical disease free survival (bDFS). CRP levels were measured in pretreatment samples. An exploratory panel of related cytokines was also measured including: monocyte chemotactic protein-1, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-23, and tumor necrosis factor. The primary endpoint examined was bDFS. Additional exploratory endpoints included overall survival, distant metastases, and toxicity events attributed to RT. RESULTS: Two hundred and two patients in RTOG/NRG 0521 had serum samples available. Median age was 66 years (48-83), and 90% of patients were White. There was not an association between CRP and bDFS (adjusted hazard ratio [HR], 1.07 per 1 log increase in CRP; 95% confidence interval, 0.83-1.38; P = .60). In the exploratory, unplanned analysis, pretreatment IL-10 was significantly associated with worse bDFS (adjusted HR, 1.61 per log increase; P = .0027) and distant metastases (HR, 1.55 per log increase; P = .028). The association of IL-10 with bDFS was maintained on a multiplicity adjustment. The exploratory analyses of pretreatment levels of interferon-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with grade 2 or higher pollakiuria (adjusted odds ratio, 0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all P < .05), and IL-6 was negatively associated with grade 2 or higher erectile dysfunction (odds ratio, 0.62; P = .027). CONCLUSIONS: Pretreatment CRP was not associated with a poorer bDFS after RT. In a hypothesis- generating analysis, higher baseline levels of IL-10 were associated with lower rates of bDFS. These findings require additional prospective evaluation.


Assuntos
Citocinas , Imunidade , Inflamação , Neoplasias da Próstata , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/análise , Citocinas/sangue , Intervalo Livre de Doença , Humanos , Inflamação/sangue , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangue , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/radioterapia
19.
Asia Pac J Clin Nutr ; 31(2): 229-241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35766559

RESUMO

BACKGROUND AND OBJECTIVES: Adverse environmental factors in tunnels increase the occurrence of respiratory and intestinal inflammatory disease, which is seriously harmful to worker health. It is reported that medium-chain triglycerides (MCT) can improve immune status and alter the gut microflora. This study investigates MCT effects on immune status and gut microbiota among tunnel workers. METHODS AND STUDY DESIGN: Forty-five workers were randomly divided into an MCT group (n=30) and control group (n=15), where they ingested MCT-milk or a placebo milk for 12 weeks, respectively. The primary outcome measure was the incidence of respiratory infection and diarrhea. Secondary outcomes were changes in serum immune-related markers and changes in gut microbiota. RESULTS: The incidence of diarrhea in MCT group was significantly decreased after 4 weeks (p<0.01), with no significant differences in the control group. MCT reduced the level of pro-inflammatory cytokines (TNF-α, CRP, and IL-6) and enhanced the anti-inflammatory cytokines (IL-10, C3, C4, IgA, IgG, and IgM), respectively (p<0.01). The Chao index was reduced (p<0.01) and microbiota composition changed significantly after 12 weeks of MCT intervention. MCT reduced the abundance of Bacteroides, Roseburia, Ruminococcus_1, Lachnospira and increased that of Blautia and Fusicatenibacter at the genus level (p<0.01). CONCLUSIONS: The consumption of MCT reduces diarrhea occurrence and improves serum immune profiles together with gut microbiomics in tunnel workers.


Assuntos
Diarreia , Microbioma Gastrointestinal , Enteropatias , Triglicerídeos , Anticorpos/sangue , China , Citocinas/sangue , Diarreia/terapia , Humanos , Inflamação/terapia , Enteropatias/terapia , Doenças Profissionais/terapia , Triglicerídeos/administração & dosagem
20.
Atherosclerosis ; 351: 18-25, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35605368

RESUMO

BACKGROUND AND AIMS: Despite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes - key determinants of inflammation propagation versus resolution - and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke. METHODS: We investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models. RESULTS: We observed associations of intermediate monocytes, early-activated CD4+ T cells, and both CD4+ and CD8+ T cells producing interleukin-4 after cytokine stimulation (Th2 and Tc2, respectively) with higher risk for incident stroke; effect sizes ranged from 35% to 62% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women. CONCLUSIONS: Circulating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention.


Assuntos
Aterosclerose , Interleucina-4 , Acidente Vascular Cerebral , Aterosclerose/epidemiologia , Aterosclerose/imunologia , Aterosclerose/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos , Citocinas/biossíntese , Citocinas/sangue , Citocinas/imunologia , Feminino , Seguimentos , Humanos , Incidência , Inflamação , Interleucina-4/biossíntese , Interleucina-4/sangue , Interleucina-4/imunologia , AVC Isquêmico/sangue , AVC Isquêmico/epidemiologia , AVC Isquêmico/imunologia , Ativação Linfocitária/imunologia , Masculino , Monócitos/imunologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia , Subpopulações de Linfócitos T/imunologia
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