RESUMO
OBJECTIVE: This study aimed to evaluate inflammatory biomarkers in patients undergoing peritoneal dialysis and investigate their association with all-cause mortality or transfer to hemodialysis. METHODS: This prospective cohort study included 43 patients undergoing peritoneal dialysis. Plasma levels of cytokines were measured using flow cytometry and capture enzyme-linked immunosorbent assay. Biomarkers were categorized based on their respective median values. Survival analysis was conducted using the Kaplan-Meier estimator, considering two outcomes: all-cause mortality and transfer to hemodialysis. RESULTS: After adjusting for confounding factors, plasma levels above the median of the levels of CCL2 and plasma, as well as below the median of TNF-α, and the median of dialysate IL-17 levels, were associated with an increased risk of experiencing the specified outcomes after approximately 16 months of follow-up. CONCLUSION: These findings suggest that inflammatory biomarkers may be a valuable tool for predicting all-cause mortality and transfer to hemodialysis in patients undergoing peritoneal dialysis.
Assuntos
Biomarcadores , Inflamação , Diálise Peritoneal , Humanos , Diálise Peritoneal/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos Prospectivos , Inflamação/sangue , Inflamação/mortalidade , Idoso , Estimativa de Kaplan-Meier , Ensaio de Imunoadsorção Enzimática , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Falência Renal Crônica/sangue , Adulto , Citocinas/sangue , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/análise , Quimiocina CCL2/sangue , Quimiocina CCL2/análise , Diálise Renal/mortalidade , Fatores de Risco , Interleucina-17/sangue , Causas de Morte , Citometria de FluxoRESUMO
Background: The purpose of this study was to investigate the diagnostic value of IL-17 detection in bronchoalveolar lavage fluid (BALF) and plasma samples from nonneutropenic patients with invasive pulmonary aspergillosis. Methods: We retrospectively collected data on non-neutropenic patients who were suspected to have IPA admitted to the Third Affiliated Hospital of Soochow University between March 2020 to January 2023. IL-17 and GM were measured using enzyme-linked immunosorbent assays. Results: A total of 281 patients were enrolled in this study, of which 62 had proven or probable IPA and the remaining 219 patients were controls. The plasma and BALF IL-17 levels were significantly higher in the IPA group compared with the control group. The plasma GM, plasma IL17, BALF GM, and BALF IL17 assays had sensitivities of 56.5%, 72.6%, 68.7%, and 81.2%, respectively, and specificities of 87.7%, 69.4%, 91.9%, and 72.6%, respectively. The sensitivity of IL17 in plasma and BALF was higher than that of GM. Plasma GM in combination with IL-17 increases the sensitivity but does not decrease the diagnostic specificity of GM testing. The diagnostic sensitivity and specificity of BALF GM combined with IL-17 for IPA in non-neutropenic patients were greater than 80% and there was a significant increase in sensitivity compared with BALF GM. Conclusions: Plasma and BALF IL-17 levels were significantly higher in non-neutropenic patients with IPA. The sensitivity of plasma and BLAF IL-17 for diagnosing IPA in non-neutropenic patients was superior to that of GM. Combined detection of lavage fluid GM and IL17 significantly improves the diagnosis of IPA in non-neutropenic patients. The combined detection of GM and IL-17 in plasma also contributes to the diagnosis of IPA in patients who cannot tolerate invasive procedures.
Assuntos
Líquido da Lavagem Broncoalveolar , Interleucina-17 , Aspergilose Pulmonar Invasiva , Humanos , Líquido da Lavagem Broncoalveolar/química , Interleucina-17/sangue , Interleucina-17/metabolismo , Interleucina-17/análise , Masculino , Feminino , Aspergilose Pulmonar Invasiva/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Sensibilidade e Especificidade , Biomarcadores/sangue , Biomarcadores/análise , Ensaio de Imunoadsorção EnzimáticaRESUMO
OBJECTIVE: Aim: This study aimed to prove the role of IL-17 on the clinical outcomes of septic patients. PATIENTS AND METHODS: Materials and Methods: This study used a systematic review and meta-analysis design. Data were obtained by searching articles published between January 2001 and June 2022 in Pubmed, Science Direct, Scopus, and Medline databases to evaluate Interleukin-17 on clinical outcomes in septic patients. Only human studies were used in this study. Meta-analysis was undertaken using random effects models. RESULTS: Results: Fourteen published studies were eligible, and four studies were included in the meta-analysis. Meta-analysis of the ratio of means (RoM) IL-17 concentration demonstrated a 5.96-fold higher level in non-survivor septic patients compared with survivors (four studies; n = 194 patients; RoM=5.96; 95% CI, 3.51-10.31; p < 0.00001; I2 = 92%). CONCLUSION: Conclusions: IL-17 levels were significantly elevated in non-survivor and predicted mortality of septic patients.
Assuntos
Interleucina-17 , Sepse , Humanos , Interleucina-17/sangue , Sepse/mortalidade , Biomarcadores/sangue , PrognósticoRESUMO
To analyze the role of interleukin IL-17A and IL-10 polymorphisms in susceptibility to juvenile idiopathic arthritis (JIA), 98 Finnish children and adolescents with JIA were studied. Data from the 1000 Genomes Project, consisting of 99 healthy Finns, served as the controls. The patients were analyzed for four IL-17A and three IL-10 gene-promoter polymorphisms, and the serum IL-17A, IL-17F, IL-10, and IL-6 levels were determined. The IL-17A rs8193036 variant genotypes (CT/CC) were more common among the patients than controls, especially in those with polyarthritis (OR 1.93, 95% CI 1.11-3.36; p = 0.020). IL-17A rs2275913 minor allele A was more common in patients (OR 1.45, 95% Cl 1.08-1.94; p = 0.014) and especially among patients with oligoarthritis and polyarthritis than the controls (OR 1.61, 95%CI 1.06-2.43; p = 0.024). Carriers of the IL-17A rs4711998 variant genotype (AG/AA) had higher serum IL-17A levels than those with genotype GG. However, carriers of the variant genotypes of IL-17A rs9395767 and rs4711998 appeared to have higher IL-17F levels than those carrying wildtype. IL-10 rs1800896 variant genotypes (TC/CC) were more abundant in patients than in the controls (OR 1.97, 95%CI 1.06-3.70; p = 0.042). Carriers of the IL-10 rs1800896 variant genotypes had lower serum levels of IL-17F than those with wildtype. These data provide preliminary evidence of the roles of IL-17 and IL-10 in the pathogenesis of JIA and its subtypes in the Finnish population. However, the results should be interpreted with caution, as the number of subjects included in this study was limited.
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Artrite Juvenil , Predisposição Genética para Doença , Interleucina-10 , Interleucina-17 , Polimorfismo de Nucleotídeo Único , Humanos , Artrite Juvenil/genética , Artrite Juvenil/sangue , Interleucina-17/genética , Interleucina-17/sangue , Interleucina-10/genética , Interleucina-10/sangue , Criança , Masculino , Feminino , Finlândia , Adolescente , Pré-Escolar , Genótipo , Alelos , Estudos de Casos e Controles , Frequência do Gene , Regiões Promotoras GenéticasRESUMO
BACKGROUND: Aortic endothelial diastolic dysfunction is an early complication of diabetes and the abnormal differentiation of Th17 cells is involved in the development of diabetes. However, the exact role of exercise on regulating the Th17 cells differentiation and the underlying molecular mechanisms remain to be elucidated in diabetic mice. METHODS: db/db and db/m+ mice were randomly divided into exercise and sedentary groups. Mice in exercise group were exercised daily, 6 days/week, for 6 weeks and mice in sedentary groups were placed on a nonmoving treadmill for 6 weeks. Vascular endothelial function was measured via wire myograph and the frequencies of Th17 from peripheral blood in mice were assessed via flow cytometry. RESULTS: Our data showed that exercise improved insulin resistance and aortic endothelial diastolic function in db/db mice. In addition, the proportion of Th17 cells and IL-17A level in peripheral blood of db/db mice were significantly increased, and exercise could promote Th17 cell differentiation and reduce IL-17A level. More importantly, STAT3 or ROR-γt inhibitors could promote Th17 cell differentiation in db/db mice, while exercise significantly down-regulated p-STAT3/ROR-γt signaling in db/db mice, suggesting that exercise regulated Th17 differentiation through STAT3/ROR-γt signaling. CONCLUSIONS: This study demonstrated that exercise improved vascular endothelial function in diabetic mice via reducing Th17 cell differentiation through p-STAT3/ROR-γt pathway, suggesting exercise may be an important non-pharmacological intervention strategy for the treatment of diabetes-related vascular complications.
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Diferenciação Celular , Diabetes Mellitus Experimental , Interleucina-17 , Condicionamento Físico Animal , Fator de Transcrição STAT3 , Células Th17 , Vasodilatação , Animais , Camundongos , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Vasodilatação/fisiologia , Fator de Transcrição STAT3/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/terapia , Masculino , Interleucina-17/sangue , Interleucina-17/metabolismo , Endotélio Vascular/fisiopatologia , Resistência à Insulina/fisiologia , Transdução de Sinais , Camundongos Endogâmicos C57BL , Aorta/fisiopatologiaRESUMO
In recent times, the pathogenesis of generalized anxiety disorder (GAD) and the influence of pro- and anti-inflammatory cytokines on it have garnered considerable interest. Cytokine research, especially Th-17 cytokine research on GAD patients, is limited. Here, we aim to assess the role of interleukin-17A (IL-17A) and interleukin-23A (IL-23A) in the pathophysiology and development of GAD. This investigation included 50 GAD patients and 38 age-sex-matched healthy controls (HCs). A psychiatrist diagnosed patients with GAD and assessed symptom severity using the DSM-5 and the GAD-7 scales. The serum concentrations of IL-17A and IL-23A were determined using commercially available ELISA kits. GAD patients exhibited elevated levels of IL-17A (77.14 ± 58.30 pg/ml) and IL-23A (644.90 ± 296.70 pg/ml) compared to HCs (43.50 ± 25.54 pg/ml and 334.40 ± 176.0 pg/ml). We observed a positive correlation between disease severity and cytokine changes (IL-23A: r = 0.359, p = 0.039; IL-17A: r = 0.397, p = 0.032). These findings indicate that IL-17A and IL-23A may be associated with the pathophysiology of GAD. ROC analysis revealed moderately higher AUC values (IL-23A: 0.824 and IL-17A: 0.710), demonstrating their potential to discriminate between patients and HCs. Also, the sensitivity values of both cytokines were relatively higher (IL-23A: 80.49% and IL-17A: 77.27%). According to the present findings, there may be an association between peripheral serum levels of IL-17A and IL-23A and the pathophysiology and development of GAD. These altered serum IL-17A and IL-23A levels may play a role in directing the early risk of developing GAD. We recommend further research to ascertain their exact role in the pathophysiology and their performance as risk assessment markers of GAD.
Assuntos
Transtornos de Ansiedade , Interleucina-17 , Subunidade p19 da Interleucina-23 , Humanos , Interleucina-17/sangue , Masculino , Feminino , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/fisiopatologia , Adulto , Subunidade p19 da Interleucina-23/sangue , Estudos de Casos e Controles , Biomarcadores/sangue , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Acute mountain sickness (AMS) is the most prevalent condition resulting from hypobaric hypoxia (HH) at high altitudes. Although evidence suggests the involvement of inflammatory cytokines in AMS development, there is currently a lack of reports on variations in cytokine levels between individuals susceptible to AMS and those resistant to AMS prior to ascending to high altitude. Thus our current study aims to assess the predictive capability for AMS occurrence by evaluating differences in cytokine levels at low altitudes. METHODS: The present study recruited 48 participants, who ascended from low altitude to middle high-altitude (3700 m) and further to extreme high-altitude (5000 m). Based on Lake Louise Score (LLS) at the two high altitudes, participants were categorized into severe AMS-susceptible (sAMS), moderate AMS-susceptible (mAMS), and non-AMS groups. The Bio-Plex MAGPIX System was employed to measure plasma levels of 11 inflammatory cytokines. Cytokines at low altitude and middle high-altitude were analyzed through receiver operating characteristic (ROC) analysis to obtain area under the ROC curve (AUROC), sensitivity, and specificity. RESULTS: Based on LLS at 3700 m, we initially categorized the study subjects into the sAMS group (n = 8) and the Non-AMS group (n = 40). Among individuals in the non-AMS group (n = 40) at the altitude of 3700 m, those who developed AMS at the altitude of 5000 m were assigned to the mAMS group (n = 17), whereas those who did not experience AMS were included into the non-AMS group (n = 23). The concentration of TNF-α at low altitude exhibited robust predictive performance for predicting AMS occurrence at the altitude of 3700 m. Among the non-AMS group at the altitude of 3700 m, we identified that the concentration of IL-2 and IL-17A demonstrated high efficacy in predicting the onset of AMS following ascent to 5000 m. In addition, differentially expressed cytokines including IL-17A, TNF-α and IL-2 at low altitude possessed discriminatory potential among the three groups at 5000 m.. CONCLUSION: We posited that the levels of TNF-α, IL-2, IL-17A in serum of low altitude could be considered as potential biomarkers to predict the occurrence of AMS at high altitude. NEW & NOTEWORTHY: Through the two comparisons at different two altitudes (baseline level and 3700 m), we provided a model to progressively screen individuals who are susceptible and resistant to different high altitudes (3700 m and 5000 m). TNF-α could firstly screen out the AMS susceptible individuals at the altitude of 3700 m. And through its combination with IL-2 and IL-17A, we could further screen out AMS susceptible individuals at the altitude of 5000 m.
Assuntos
Doença da Altitude , Altitude , Biomarcadores , Interleucina-17 , Interleucina-2 , Fator de Necrose Tumoral alfa , Humanos , Doença da Altitude/sangue , Masculino , Biomarcadores/sangue , Interleucina-17/sangue , Adulto , Fator de Necrose Tumoral alfa/sangue , Feminino , Interleucina-2/sangue , Doença Aguda , Curva ROC , Pessoa de Meia-IdadeRESUMO
Rheumatoid Arthritis (RA) is a chronic, progressive autoimmune disease, involves an intimate relationship between immune cells and cytokines and results in decreased lifespans and higher mortality rates. The goal of the current study was to investigate the impact of MicroRNA (miRNA)146a and interleukin-17 (IL-17) as prognosis markers in RA patients. This case-control study included 120 RA patients who visited the Rheumatology unit at Al-Saddar Medical City in the governorate of Najaf, and 30 normal controls. Venous blood samples were collected from both patients and controls. Blood samples were used for measuring IL-17 levels using an enzyme linked immunosorbent assay (ELISA) testing, and miRNA146a by the reverse transcription polymerase chain reaction (RT-PCR). The results showed higher frequency of RA in women than in men with elevate incidence in patients aged 40-59 years and 1-2 years RA disease duration of. The level of IL-17 was significantly higher in serum of RA patients compared with the control group (p < 0.0001). IL-17 level was significantly increased among the patients in RA stage 4 (p < 0.0001). IL-17 level was significantly increased in patients without treatment compared with treated patients. The expression of miRNA-146a was significantly higher in the patients' group than control group. In conclusion, IL-17 may play critical role in chronic inflammation and can be used as diagnostic biomarker for RA. miRNA-146a is overexpressed in RA patient relative to healthy individuals and it acts as a negative regulator for IL-17.
Assuntos
Artrite Reumatoide , Interleucina-17 , MicroRNAs , Humanos , Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Artrite Reumatoide/diagnóstico , Interleucina-17/sangue , Interleucina-17/genética , MicroRNAs/sangue , MicroRNAs/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos de Casos e Controles , Biomarcadores/sangue , Progressão da DoençaRESUMO
PROBLEM: Adenomyosis (AM) is associated with immune response and inflammation. However, the role of T cell subsets in AM development has not been thoroughly understood. METHOD OF STUDY: Patients with focal or diffuse AM were recruited. Serum cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). Different T cell subsets in the blood and ectopic endometrium were determined by flow cytometry. RESULTS: Serum interleukin-6 (IL-6) and macrophage-colony-stimulating factor (GM-CSF) were increased in patients with focal or diffuse AM before focused ultrasound ablation surgery (FUAS), but not after FUAS. Compared with the healthy control, the frequencies of CD8+ interferon-gamma (IFN-γ)-expressing cytotoxic T lymphocytes (CTLs), interleukin-17A (IL-17A)-expressing Tc17 cells, CD4+ T helper 1 (Th1) cells, and GM-CSF-expressing T helper (ThGM) cells were up-regulated in the blood of patients with AM, especially those with diffuse AM. However, these changes were eradicated after FUAS. Meanwhile, the frequencies of these T cell subsets were positively correlated with the CA-125 level. Furthermore, these T cell subsets were also increased in ectopic endometrium. CONCLUSIONS: Our study delineates for the first time the presence of CTLs, Tc17 cells, Th1, and ThGM cells in the blood and ectopic endometrium in AM. The results imply that T cell response might impact AM development.
Assuntos
Adenomiose , Endométrio , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Células Th1 , Humanos , Feminino , Endométrio/imunologia , Endométrio/patologia , Adulto , Adenomiose/imunologia , Adenomiose/sangue , Adenomiose/patologia , Células Th1/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Linfócitos T Citotóxicos/imunologia , Pessoa de Meia-Idade , Interleucina-17/metabolismo , Interleucina-17/sangue , Interleucina-6/sangue , Interleucina-6/metabolismo , Células Th17/imunologia , Linfócitos T Auxiliares-Indutores/imunologiaRESUMO
BACKGROUND: Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients. OBJECTIVE: This study examined the association between the gene expression levels of upstream (IL-25, IL-33, and TSLP) and downstream cytokines (IL-5, IL-4, and IL-13) in the T2 inflammatory pathway with a 12-month follow-up of exacerbation, lung function, and steroid use. METHODS: Transcriptomic sequencing analysis was performed on peripheral blood mononuclear cells from 279 adult asthmatics. Survival analysis and linear mixed-effect models were used to investigate potential differences between the high-level and low-level gene expression groups and the clinical outcomes. Analysis was performed separately for the upstream, downstream, and all 6 cytokines. RESULTS: In general, T2 inflammatory cytokine gene expression showed a weak correlation with blood eosinophil counts (all r < 0.1) and clinical outcomes. Among moderate-to-severe eosinophilic asthma (MSEA) patients, individuals with elevated levels of downstream cytokines were at increased risk of time-to-first exacerbation (p = 0.044) and a greater increase of inhaled corticosteroid use over time (p = 0.002) compared to those with lower gene expression. There was no association between baseline T2 inflammatory cytokine gene expression and the longitudinal changes in lung function over time among MSEA patients. CONCLUSION: These findings suggest that, among MSEA patients, the gene expression levels of downstream cytokines in the T2 inflammatory pathway may serve as indicators for endotyping asthma.
Assuntos
Asma , Citocinas , Interleucina-13 , Interleucina-4 , Leucócitos Mononucleares , Transcriptoma , Humanos , Asma/genética , Asma/sangue , Asma/imunologia , Asma/tratamento farmacológico , Masculino , Feminino , Leucócitos Mononucleares/metabolismo , Adulto , Pessoa de Meia-Idade , Citocinas/genética , Citocinas/sangue , Estudos Longitudinais , Interleucina-4/genética , Interleucina-4/sangue , Interleucina-13/genética , Interleucina-13/sangue , Eosinófilos , Linfopoietina do Estroma do Timo , Interleucina-5/genética , Interleucina-5/sangue , Interleucina-33/genética , Interleucina-33/sangue , Interleucina-17/genética , Interleucina-17/sangue , Corticosteroides/uso terapêutico , Perfilação da Expressão Gênica/métodos , Progressão da Doença , Índice de Gravidade de DoençaRESUMO
Introduction: Depressive syndrome (DS) is a common complication during pregnancy and the postpartum period, and is triggered by multiple organic/genetic and environmental factors. Clinical and biochemical follow-up is essential for the early diagnosis and prognosis of DS. The protozoan Toxoplasma gondii causes infectious damage to the fetus during parasite primary-infection. However, in long-term infections, pregnant women develop immune protection to protect the fetus, although they remain susceptible to pathological or inflammatory effects induced by T. gondii. This study aimed to investigate plasma inflammatory biomarkers in pregnant women seropositive and seronegative for T. gondii, with diagnoses of minor and moderate/severe DS. Methods: Pregnant women (n=45; age=18-39 years) were recruited during prenatal care at health centers in Ouro Preto, Minas Gerais, Brazil. Participants were asked to complete a socio-demographic questionnaire to be submitted to well-standardized DS scale calculators (Beck Depression Inventory Questionnaire, Edinburgh Postnatal Depression Scale, and Major Depressive Episode Module). Additionally, 4 mL of blood was collected for plasma neuroserpin, CCL2, IL-17A, and IL-33 analysis. Results: Pregnant volunteers with chronic T. gondii contact were all IgG+ (44%; n=21) and exhibited increased plasma IL-33, IL-17A, and neuroserpin levels, but not CCL2, compared to uninfected pregnant women. Using Beck's depression inventory, we observed an increase in plasma IL-17A and IL-33 in women with T. gondii infeCction diagnosed with mild DS, whereas neuroserpin was associated with minor and moderate/severe DS. Discussion: Our data suggest a close relationship between DS in pregnant women with chronic T. gondii infection and neurological conditions, which may be partially mediated by plasma neuroserpin, IL-33, and IL-17A levels.
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Biomarcadores , Interleucina-17 , Interleucina-33 , Toxoplasma , Toxoplasmose , Humanos , Feminino , Gravidez , Interleucina-17/sangue , Adulto , Toxoplasmose/sangue , Toxoplasmose/diagnóstico , Toxoplasmose/imunologia , Toxoplasmose/psicologia , Biomarcadores/sangue , Interleucina-33/sangue , Adulto Jovem , Toxoplasma/imunologia , Adolescente , Complicações Parasitárias na Gravidez/sangue , Complicações Parasitárias na Gravidez/imunologia , Complicações Parasitárias na Gravidez/diagnóstico , Depressão/sangue , Depressão/imunologia , Depressão/diagnósticoRESUMO
OBJECTIVES: To investigate the expression of microRNA-142 (miR-142) in children with autoimmune thyroid disease (AITD) and its relationship with the imbalance of helper T cell 17 (Th17) and regulatory T cell (Treg). METHODS: A total of 89 children hospitalized for AITD from January 2019 to December 2022 were prospectively selected as the study subjects, including 48 children with Graves' disease (GD group) and 41 children with Hashimoto's thyroiditis (HT group). Additionally, 55 healthy children undergoing physical examinations during the same period were selected as the control group. The differences in serum miR-142, antithyroglobulin antibody (TGAb), antithyroperoxidase antibody (TPOAb), Th17/Treg, and interleukin-17 (IL-17) expression were compared among the groups. RESULTS: The expression of miR-142, TPOAb, TGAb, Th17, Th17/Treg, and IL-17 in the GD group and HT group was higher than that in the control group, while Treg was lower than that in the control group (P<0.05). Pearson correlation analysis revealed that in the GD group, miR-142 was positively correlated with TPOAb, TGAb, Th17, Th17/Treg, and IL-17 (r=0.711, 0.728, 0.785, 0.716, 0.709, respectively; P<0.001) and negatively correlated with Treg (r=-0.725, P<0.001); in the HT group, miR-142 was positively correlated with TPOAb and TGAb (r=0.752, 0.717, respectively; P<0.001). CONCLUSIONS: miR-142 is highly expressed in children with AITD, and its expression may be related to the Th17/Treg imbalance in children with GD.
Assuntos
Interleucina-17 , MicroRNAs , Linfócitos T Reguladores , Células Th17 , Humanos , MicroRNAs/sangue , Células Th17/imunologia , Criança , Masculino , Feminino , Linfócitos T Reguladores/imunologia , Interleucina-17/sangue , Doença de Hashimoto/imunologia , Doença de Hashimoto/genética , Doença de Hashimoto/sangue , Pré-Escolar , Doença de Graves/imunologia , Doença de Graves/genética , Adolescente , Autoanticorpos/sangueRESUMO
CD20+ T cells constitute a small subset of T cells. These are found among CD4+, CD8+, CD4+CD8+, CD4-CD8- T, and TCRγδ+ T cells, and have been poorly characterized. The aim of this study was to characterize peripheral blood (PB) CD20+ T cells and compare them to their PB CD20- T cell counterparts. PB from 17 healthy individuals was collected. The distribution of CD20+ T cells among maturation-associated T cells compartments (naïve, central memory, transitional memory, effector memory, and effector T cells), their polarization, activation status, and expression of immune-regulatory proteins were evaluated by flow cytometry. Their function was also assessed, by measuring IFN-γ, TNF-α, and IL-17 production. Compared with CD20- T cells, CD20+ T cells represent a higher proportion of transitional memory cells. Furthermore, CD20+ T cells display a proinflammatory phenotype, characterized by the expansion of Th1, Th1/17, and Tc1 cell subsets , associated to a high expression of activation (CD25) and exhaustion (PD-1) markers. In addition, the simultaneous production of the proinflammatory cytokines IFN-γ, TNF-α, and IL-17 was also detected in CD4+CD20+ T cells. Our results show that CD20+ T cells are phenotypically and functionally different from CD20- T cells, suggesting that these cells are a distinct subset of T cells.
Assuntos
Antígenos CD20 , Citometria de Fluxo , Humanos , Antígenos CD20/imunologia , Masculino , Feminino , Adulto , Interferon gama , Fator de Necrose Tumoral alfa , Interleucina-17/sangue , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Ativação Linfocitária/imunologia , Pessoa de Meia-Idade , Memória Imunológica/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Citocinas/metabolismo , Células T de Memória/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologiaRESUMO
We aimed to observe the effects of adipose-derived mesenchymal stem cells (ADSCs) on T helper 17 (Th17)/regulatory T cells (Treg) and T-box transcription factor (T-bet)/GATA-binding protein 3 (GATA-3) in model mice with primary immune thrombocytopenia (ITP). 32 BALB/C mice were selected. ADSCs were isolated from 2 mice and cultured. The other 30 mice were randomly divided into the normal control group, the ITP model control group, and the ITP experimental group. Platelet count (PLT), Th17/Treg cells, related serum cytokines [interleukin-6 (IL-6), IL-17A, IL-10, and transforming growth factor ß1 (TGF-ß1)], T-bet and GATA-3 mRNA levels in peripheral blood mononuclear cells (PBMCs) in the 3 groups were detected. PLT and Treg in the ITP experimental group were significantly lower than those in the normal control group (P<0.05), but significantly higher than those in the ITP model control group (P<0.05). Th17 and Th17/Treg in the ITP experimental group were significantly higher than those in the normal control group (P<0.05), but significantly lower than those in the ITP model control group (P<0.05). Serum IL-6 and IL-17A levels, and T-bet mRNA levels in the ITP experimental group were significantly higher than those in the normal control group (P<0.05), but significantly lower than those in the ITP model control group (P<0.05). Serum IL-10 and TGF-ß levels, and GATA-3 mRNA levels in the ITP experimental group were significantly lower than those in the normal control group (P<0.05), but significantly higher than those in the ITP model control group (P<0.05). ADSCs can effectively regulate Th17/Treg balance and improve T-bet/GATA-3 mRNA expression levels in ITP model mice.
Assuntos
Modelos Animais de Doenças , Fator de Transcrição GATA3 , Células-Tronco Mesenquimais , Camundongos Endogâmicos BALB C , Proteínas com Domínio T , Linfócitos T Reguladores , Células Th17 , Animais , Feminino , Masculino , Camundongos , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Citocinas/metabolismo , Citocinas/sangue , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Interleucina-10/genética , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-17/sangue , Interleucina-17/metabolismo , Interleucina-17/genética , Interleucina-6/sangue , Interleucina-6/metabolismo , Interleucina-6/genética , Células-Tronco Mesenquimais/metabolismo , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/imunologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/imunologia , Células Th17/metabolismo , Células Th17/imunologia , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/sangueRESUMO
Interleukin (IL)-17A contributes to hypertension in preclinical models. T helper 17 and dendritic cells are activated by NaCl, which could involve the epithelial Na+ channel (ENaC). We hypothesized that the ENaC blocker amiloride reduces plasma IL-17A and related cytokines in patients with hypertension. Concentrations of IL-17A, IFN-γ, TNF, IL-6, IL-1ß, and IL-10 were determined by immunoassays in plasma from two patient cohorts before and after amiloride treatment: 1) patients with type 2 diabetes mellitus (T2DM) and treatment-resistant hypertension (n = 69, amiloride 5-10 mg/day for 8 wk) and 2) patients with hypertension and type 1 diabetes mellitus (T1DM) (n = 29) on standardized salt intake (amiloride 20-40 mg/day, 2 days). Plasma and tissue from ANG II-hypertensive mice with T1DM treated with amiloride (2 mg/kg/day, 4 days) were analyzed. The effect of amiloride and benzamil on macrophage cytokines was determined in vitro. Plasma cytokines showed higher concentrations (IL-17A â¼40-fold) in patients with T2DM compared with T1DM. In patients with T2DM, amiloride had no effect on IL-17A but lowered TNF and IL-6. In patients with T1DM, amiloride had no effect on IL-17A but increased TNF. In both cohorts, blood pressure decline and plasma K+ increase did not relate to plasma cytokine changes. In mice, amiloride exerted no effect on IL-17A in the plasma, kidney, aorta, or left cardiac ventricle but increased TNF in cardiac and kidney tissues. In lipopolysaccharide-stimulated human THP-1 macrophages, amiloride and benzamil (from 1 nmol/L) decreased TNF, IL-6, IL-10, and IL-1ß. In conclusion, inhibition of ENaC by amiloride reduces proinflammatory cytokines TNF and IL-6 but not IL-17A in patients with T2DM, potentially by a direct action on macrophages.NEW & NOTEWORTHY ENaC activity may contribute to macrophage-derived cytokine release, since amiloride exerts anti-inflammatory effects by suppression of TNF and IL-6 cytokines in patients with resistant hypertension and type 2 diabetes and in THP-1-derived macrophages in vitro.
Assuntos
Amilorida , Diabetes Mellitus Tipo 2 , Bloqueadores do Canal de Sódio Epitelial , Hipertensão , Interleucina-17 , Interleucina-6 , Fator de Necrose Tumoral alfa , Amilorida/farmacologia , Amilorida/uso terapêutico , Humanos , Interleucina-17/sangue , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/imunologia , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Hipertensão/tratamento farmacológico , Hipertensão/sangue , Feminino , Bloqueadores do Canal de Sódio Epitelial/farmacologia , Fator de Necrose Tumoral alfa/sangue , Idoso , Camundongos , Canais Epiteliais de Sódio/metabolismo , Canais Epiteliais de Sódio/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Anti-Hipertensivos/farmacologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangueRESUMO
BACKGROUND: Interleukin-17 (IL-17) has been hypothesized to be involved in ischemic cardiovascular disease (ICVD). However, the association of IL-17 with ICVD remained unclear. The aim of this study was to systematically analyze the available evidence regarding the association between IL-17 and ICVD. METHODS: We searched the PubMed, Web of Science, Cochrane Library, and Embase databases up to October 2023 to identify publications on the association between IL-17 and ICVD. The merged results were analyzed using a random effects model for meta-analysis and subgroup analysis. RESULTS: A total of 955 publications were initially identified in our search and screened; six studies were eventually included in the analysis. The average age of study participants was 60.3 ± 12.6 years and 65.5% were men. There was a high degree of heterogeneity among studies. The results showed that IL-17 level were higher in the case group than those in the control group (standardized mean difference, SMD = 1.60, 95% confidence interval (95% CI): 0.53-2.66, P = 0.003). In sensitivity analysis, the merged results showed good robustness. Additionally, subgroup analysis showed that race and ethnicity, sample size, and detection methods were significant factors influencing heterogeneity in the published studies. CONCLUSION: Our finding revealed that increased IL-17 level contributed to the development of ICVD, suggesting IL-17 as a potential risk marker. Further research is needed to establish IL-17 as a therapeutic biomarker of ICVD.
Assuntos
Biomarcadores , Interleucina-17 , Isquemia Miocárdica , Humanos , Interleucina-17/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Isquemia Miocárdica/sangue , Isquemia Miocárdica/imunologia , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiologia , Medição de Risco , Biomarcadores/sangue , Regulação para Cima , Fatores de Risco , PrognósticoRESUMO
Obstructive sleep apnea (OSA) is a chronic inflammatory disease characterized by partial or complete upper airway obstruction during sleep. We aimed to evaluate serum/plasma levels of several cytokines (interleukin [IL]-6, IL-12, IL-17, IL-18, and IL-23) in a systematic review meta-analysis in both adults and children with OSA compared with controls. We conducted a comprehensive search of 4 digital databases (PubMed, Web of Science, Scopus, and Cochrane Library) up until October 19, 2023, without any limitations. For our meta-analysis, we used Review Manager, version 5.3, and displayed the data as the standardized mean difference (SMD) and 95% confidence interval (CI) to assess the correlation between cytokine levels and OSA. We utilized Comprehensive Meta-Analysis version 3.0 software to conduct bias analyses, meta-regression, and sensitivity analyses. From 1881 records, 84 articles were included in the systematic review and meta-analysis. In adults, the pooled SMDs for IL-6 level were 0.79 (P value < 0.00001), for IL-17 level were 0.74 (P value = 0.14), and for IL-18 level were 0.43 (P value = 0.00002). In children, the pooled SMD for IL-6 was 1.10 (P value < 0.00001), for IL-12 was 0.47 (P value = 0.10), for IL-17 was 2.21 (a P value = 0.24), for IL-18 was 0.19 (P value = 0.07), and for IL-23 was 2.46 (P value < 0.0001). The subgroup analysis showed that the ethnicity, mean body mass index, and mean apnea-hypopnea index for IL-6 levels in adults and the ethnicity for IL-6 levels in children were effective factors in the pooled SMD. The findings of the trial sequential analysis revealed that adequate evidence has been obtained. The analysis of IL levels in adults and children with OSA compared with those without OSA revealed significant differences. In adults, IL-6 and IL-18 levels were significantly higher in the OSA group, while in children, only IL-6 and IL-23 levels were significantly elevated.
Assuntos
Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/sangue , Criança , Adulto , Interleucinas/sangue , Interleucina-18/sangue , Interleucina-17/sangueRESUMO
Purpose: A systematic evaluation and Meta-analysis were performed to determine the relationship between IL-17A levels in ocular aqueous and peripheral venous serum samples and diabetic retinopathy (DR). Methods: PubMed, Embase, Web of Science, and CNKI databases were searched from the time of library construction to 2023-09-20.The results were combined using a random-effects model, sensitivity analyses were performed to determine whether the arithmetic was stable and reliable, and subgroup analyses were used to look for possible sources of heterogeneity. Results: A total of 7 case-control studies were included. The level of IL-17A was higher in the Nonproliferative DR(NPDR) group than in the Non-DR(NDR) group [SMD=2.07,95%CI(0.45,3.68),P=0.01], and the level of IL-17A in the proliferating DR(PDR) group was higher than that of the NDR group [SMD=4.66,95%CI(1.23,8.08),P<0.00001]. IL-17A levels in peripheral serum and atrial fluid were significantly higher in NPDR and PDR patients than in non-DR patients in subgroup analyses, and detection of peripheral serum IL-17A concentrations could help to assess the risk of progression from NPDR to PDR. Sensitivity analyses suggested that the results of the random-effects arithmetic were stable and reliable. Subgroup analyses based on assay method and sample source showed that the choice of these factors would largely influence the relationship between IL-17A levels and DR. Conclusion: Elevated peripheral serum and ocular aqueous humor IL-17A levels in diabetic patients are associated with the risk of DR, IL-17A may serve as a potential predictor or therapeutic target for DR, and IL-17A may be an important predictor of inflammation for the progression of NPDR to PDR. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024532900.
Assuntos
Retinopatia Diabética , Interleucina-17 , Humanos , Retinopatia Diabética/sangue , Interleucina-17/sangue , Humor Aquoso/metabolismo , Estudos de Casos e Controles , Biomarcadores/sangueRESUMO
Multisystem inflammatory syndrome in children (MIS-C) shares several clinical and immunological features with Kawasaki Disease (KD) and pediatric hyperinflammation, but the immuno-phenotypic overlap among these clinical mimics is still incompletely understood. Here we analyzed serum samples from treatment-naïve patients with MIS-C (n = 31) and KD (n = 11), pediatric hyperinflammation (n = 13) and healthy controls (HC, n = 10) by proximity extension assay (PEA) to profile 184 blood biomarkers. Collectively, immunophenotypic overlap between MIS-C and hyperinflammation exceeds overlap with KD. Overexpression of IL-17A in MIS-C and KD could best separate these conditions from hyperinflammatory conditions, while those were hallmarked by overabundance of adenosin deaminase and IL-18. Depletion in serum TNF-related subfamily member 9 (TNFRSF9) and apoptosis inducing ligand (TRAIL) linked with cardiovascular manifestations and myocarditis in MIS-C. Altogether, our analysis highlights important differences in molecular marker signatures also across different MIS-C and KD cohorts and suggests several previously unidentified molecular associations in context of cardiovascular inflammation.
Assuntos
Biomarcadores , Síndrome de Linfonodos Mucocutâneos , Proteômica , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Biomarcadores/sangue , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/imunologia , Masculino , Feminino , Proteômica/métodos , Criança , Pré-Escolar , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Inflamação/sangue , Lactente , Interleucina-17/sangue , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Interleucina-18/sangue , Adenosina Desaminase/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/imunologiaRESUMO
The study presents the killer functions of circulating neutrophils: myeloperoxidase activity, the ability to generate ROS, phagocytic activity, receptor status, NETosis, as well as the level of cytokines IL-2, IL-4, IL-6, IL-17A, and IL-18, granulocyte CSF, monocyte chemotactic protein 1, and neutrophil elastase in the serum of patients with uterine myoma and endometrial cancer (FIGO stages I-III). The phagocytic ability of neutrophils in uterine myoma was influenced by serum levels of granulocyte CSF and IL-2 in 54% of the total variance. The degranulation ability of neutrophils in endometrial cancer was determined by circulating IL-18 in 50% of the total variance. In uterine myoma, 66% of the total variance in neutrophil myeloperoxidase activity was explained by a model dependent on blood levels of IL-17A, IL-6, and IL-4. The risk of endometrial cancer increases when elevated levels of monocyte chemotactic protein 1 in circulating neutrophils are associated with reduced ability to capture particles via extracellular traps (96% probability).