RESUMO
Mucosal-associated invariant T (MAIT) cells are essential in defending against infection. Sepsis is a systemic inflammatory response to infection and a leading cause of death. The relationship between the overall competency of the host immune response and disease severity is not fully elucidated. This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and retinoic acid receptor-related orphan receptor γt in patients with sepsis. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA-sequencing analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in patients with sepsis. Cell-culture experiments demonstrated that phosphoinositide 3-kinase-LDHA signaling was required for retinoic acid receptor-related orphan receptor γt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 cells in sepsis. In summary, this study reveals a new role of circulating MAIT17 in promoting sepsis severity and suggests the phosphoinositide 3-kinase-LDHA signaling as a driving force in MAIT17 responses.
Assuntos
Diferenciação Celular , Células T Invariantes Associadas à Mucosa , Sepse , Humanos , Sepse/imunologia , Sepse/patologia , Sepse/sangue , Células T Invariantes Associadas à Mucosa/imunologia , Células T Invariantes Associadas à Mucosa/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Idoso , Interleucina-17/metabolismo , Interleucina-17/sangue , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
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
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
Gestational diabetes mellitus (GDM) is a frequent and serious complication of pregnancy, often associated with obesity. Metabolic dysfunction and metainflammation are evident in both obesity and GDM. In this cross-sectional study, we aimed at defining the direct contribution of the immune system in GDM, across the main metabolic tissues, specifically focussing on elucidating the roles of obesity and GDM to the clinical outcome. Using immunoassays and multicolour flow cytometry, cytokine profiles and immune cell frequencies were measured in maternal circulation and central metabolic tissues [placenta and visceral adipose tissue (VAT)] in GDM-diagnosed (nâ =â 28) and normal glucose tolerant (nâ =â 32) women undergoing caesarean section. Participants were sub-grouped as non-obese [body mass index (BMI)â <â 30 kg/m2] or obese (BMIâ ≥â 30 kg/m2). Unsupervised data analysis was performed on the flow cytometry data set to identify functional alterations. GDM obese participants had significantly elevated circulating IL-6 and IL-17A levels. GDM non-obese participants had elevated circulating IL-12p70, elevated placental IL-17A, and VAT IFN-γ production. Unsupervised clustering of immune populations across the three biological sites simultaneously, identified different NK- and T-cell phenotypes that were altered in NGT obese and GDM non-obese participants, while a classical tissue monocyte cluster was increased in GDM obese participants. In this study, there was significant evidence of subclinical inflammation, and significant alterations in clusters of NK cells, T cells, and tissue monocyte populations in GDM. While increased adiposity assimilates with increased inflammation in the non-pregnant state, this overt relationship may not be as evident during pregnancy and warrants further examination in future longitudinal studies.
Assuntos
Diabetes Gestacional , Inflamação , Obesidade , Humanos , Feminino , Gravidez , Diabetes Gestacional/imunologia , Diabetes Gestacional/sangue , Adulto , Obesidade/imunologia , Inflamação/imunologia , Estudos Transversais , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/metabolismo , Placenta/imunologia , Placenta/metabolismo , Células Matadoras Naturais/imunologia , Interleucina-17/sangue , Citocinas/sangue , Citocinas/metabolismo , Interleucina-6/sangue , Índice de Massa Corporal , Linfócitos T/imunologia , Interferon gama/sangueRESUMO
BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that typically emerges early in childhood. This study aimed to explore the potential link between serum levels of vitamin B12 and homocysteine (Hcy) and the severity of ASD symptoms in children. METHODS: In this study, 50 children diagnosed with ASD comprised the observation group, while 50 healthy children constituted the control group. Serum levels of IL-17 A, Hcy, folate, and vitamin B12 were compared between the study group and control group, as well as among children with different degrees of ASD severity. The correlation between the Childhood Autism Rating Scale (CARS) score and serum levels of IL-17 A, Hcy, folate, and vitamin B12 was examined. Additionally, the relationship between serum IL-17 A and Hcy levels and their association with the severity ASD were explored. RESULTS: Compared to the control group, the observation group demonstrated elevated serum Hcy and IL-17 A levels alongside decreased folate and vitamin B12 levels. Individuals with severe ASD exhibited higher Hcy and IL-17 A levels but lower folate and vitamin B12 levels compared to those with mild to moderate ASD. The CARS score showed negative correlations with serum folate and vitamin B12 levels and positive correlations with serum IL-17 A and Hcy levels in ASD patients. Additionally, serum Hcy and IL-17 A levels were correlated with ASD severity. CONCLUSION: Children diagnosed with ASD presented with reduced serum vitamin B12 levels and increased levels of Hcy, potentially contributing to the onset and severity of ASD.
Assuntos
Transtorno Autístico , Homocisteína , Interleucina-17 , Criança , Humanos , Transtorno Autístico/sangue , Ácido Fólico/sangue , Interleucina-17/sangue , Vitamina B 12/sangue , Homocisteína/sangueRESUMO
BACKGROUND: Recent studies have more focused on gut microbial alteration in tuberculosis (TB) patients. However, no detailed study on gut fungi modification has been reported till now. So, current research explores the characteristics of gut microbiota (bacteria)- and mycobiota (fungi)-dysbiosis in TB patients and also assesses the correlation between the gut microbiome and serum cytokines. It may help to screen the potential diagnostic biomarker for TB. RESULTS: The results show that the alpha diversity of the gut microbiome (including bacteria and fungi) decreased and altered the gut microbiome composition of TB patients. The bacterial genera Bacteroides and Prevotella were significantly increased, and Blautia and Bifidobacterium decreased in the TB patients group. The fungi genus Saccharomyces was increased while decreased levels of Aspergillus in TB patients. It indicates that gut microbial equilibrium between bacteria and fungi has been altered in TB patients. The fungal-to-bacterial species ratio was significantly decreased, and the bacterial-fungal trans-kingdom interactions have been reduced in TB patients. A set model including Bacteroides, Blautia, Eubacterium_hallii_group, Apiotrichum, Penicillium, and Saccharomyces may provide a better TB diagnostics option than using single bacterial or fungi sets. Also, gut microbial dysbiosis has a strong correlation with the alteration of IL-17 and IFN-γ. CONCLUSIONS: Our results demonstrate that TB patients exhibit the gut bacterial and fungal dysbiosis. In the clinics, some gut microbes may be considered as potential biomarkers for auxiliary TB diagnosis.
Assuntos
Bactérias , Disbiose , Fungos , Microbioma Gastrointestinal , Humanos , Disbiose/microbiologia , Fungos/classificação , Fungos/isolamento & purificação , Fungos/genética , Masculino , Feminino , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Adulto , Pessoa de Meia-Idade , Tuberculose/microbiologia , Tuberculose/complicações , Fezes/microbiologia , Citocinas/sangue , Interleucina-17/sangueRESUMO
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
BACKGROUND: Cytokines are of utmost importance in both the physiological and pathological immune responses of the human body. This study utilized flow cytometry to measure the levels of plasma interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-17A (IL-17A) and established their reference intervals, aiming to provide data support for the diagnosis and treatment of clinical diseases. METHODS: According to the inclusion and exclusion criteria, a total of 728 reference individuals were included in this study from January 2023 to June 2023. The Kolmogorov-Smirnov test was used to analyse the distributions of plasma IL-2, IL-4, IL-5 and IL-17A. The reference intervals of plasma IL-2, IL-4, IL-5 and IL-17A were established by the unilateral percentile method (95th percentile) based on the guidelines of C28-A 3 and WS/T 402-2012. RESULTS: In this study, the levels of plasma IL-2, IL-4, IL-5 and IL-17A were nonnormally distributed. The concentrations of plasma IL-2, IL-4, IL-5 and IL-17A in healthy adults were not significantly different by sex or age (all P > 0.05). Therefore, all the reference individuals were combined into one group, and the reference intervals of plasma IL-2, IL-4, IL-5 and IL-17 were established by flow cytometry (IL-2 ≤ 10.25 pg/mL, IL-4 ≤ 9.87 pg/mL, IL-5 ≤ 3.36 pg/mL and IL-17A ≤ 9.46 pg/mL). CONCLUSIONS: We first established the reference intervals of plasma IL-2, IL-4, IL-5 and IL-17A in healthy adults based on a single-center population in the Jiangsu region in eastern China, which will provide an important reference value for evaluating human immune status and the diagnosis and treatment of clinical diseases.
Assuntos
Citometria de Fluxo , Interleucina-17 , Interleucina-2 , Interleucina-4 , Interleucina-5 , Humanos , Citometria de Fluxo/métodos , Masculino , Interleucina-17/sangue , Feminino , Adulto , Interleucina-5/sangue , China , Interleucina-2/sangue , Interleucina-4/sangue , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem , Idoso , Voluntários Saudáveis , AdolescenteRESUMO
Candida species are a normal human flora in humans' digestive and reproductive systems, oral cavity, skin, and mucosal surfaces. This study aimed to detect the immunological role of Candida infection by using some immunological markers. The results of levels in serum showed high concentrations of IgA (56.20 ± 12 pg/ml,29.55 ± 4.5 pg/ml respectively) and IgG (12.05 ± 3.218 pg/ml, 3.836 ± 1.23 pg/ml respectively) in mice infected with C. albicans and mice treated with Cefoperazone and infected with Candida with significant differences (P value < 0.05). The results showed high serum levels of IL-17(191.5 ± 42.81 pg/ml) and TLR2(7.651 ± 1.5 pg/ml) in group mice infected with C. albicans compared with negative control and group mice treated with Cefoperazone. Also, high levels of IL-17 (91.33 ± 4.816 pg/ml) and TLR2 (2.630 ± 0.5 pg/ml) in group mice treated with Cefoperazone and infected with Candida compared with negative control and group mice treated with Cefoperazone (P value < 0.05). The results of antibodies and immunological markers in the intestine showed high levels of IgA and IgG in mice infected with C.albicans (55.7 ± 4.9 pg/ml, 18.19 ± 0.63 pg/ml respectively).Also,IgA and IgG in mice treated with Cefoperazone and infected with Candida were high level (43.04 ± 2.1 pg/ml, 2.927 ± 0.2 pg/ml respectively) in mice infected with C. albicans with significant differences (P value < 0.05). The results levels of IL-17 and TLR2 were increased in mice infected with C. albicans (191.5 ± 42.81 pg/ml, 7.651 ± 1.5 pg/ml respectively) and mice treated with Cefoperazone and infected with Candida (91.33 ± 4.816 pg/ml,2.630 ± 0.5 pg/ml respectively) with significant differences (P < 0.05). In conclusion, this study demonstrated that cefoperazone treatment and infection by Candida albicans changed the microbiome components in the gut and finally can change host immune responses. It was observed that elevated levels of the antibodies production (IgA and IgG) and immunological markers (IL-17, and TLR2) in serum and the gut.
Assuntos
Candida albicans , Candidíase , Cefoperazona , Interleucina-17 , Receptor 2 Toll-Like , Animais , Candida albicans/imunologia , Candidíase/imunologia , Candidíase/tratamento farmacológico , Camundongos , Receptor 2 Toll-Like/metabolismo , Interleucina-17/metabolismo , Interleucina-17/sangue , Imunoglobulina G/sangue , Imunoglobulina A/sangue , Masculino , Feminino , Camundongos Endogâmicos BALB CRESUMO
OBJECTIVE: The objective of this study was to investigate the impact of 92 inflammatory proteins on the risk of cardiovascular disease (CVD) in patients with early rheumatoid arthritis (RA). METHODS: This study included consecutive patients with early RA recruited between 1995 and 2002. Stored plasma samples were analyzed for 92 inflammatory proteins. CVD diagnoses were retrieved from national in-patient and cause-of-death registries. Statistical analyses were predesignated as hypothesis-driven or exploratory. For the latter, proteins were selected based on principal component analysis (ie, factor loading > 0.5 within main components). Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression. RESULTS: Data on baseline levels of proteins and CVD were available for 163 patients. As hypothesized, levels of interleukin 17A (IL-17A) were associated with CVD (hazard ratio 1.35, 95% CI 1.02-1.78, adjusted for age, sex, hypertension, diabetes, smoking, and erythrocyte sedimentation rate [ESR]), although not significantly with CAD. Osteoprotegerin (OPG) levels were significantly associated with both outcomes, but only in crude models. No associations were observed for IL-6, tumor necrosis factor, monocyte chemotactic protein-1, or IL-8. In the exploratory analyses, MCP-3 in particular had significant associations with both outcomes in crude models. CONCLUSION: Circulating IL-17A at RA diagnosis predicted future CVD, although we cannot exclude the possibility that this finding is due to multiple testing. The association was independent of traditional CVD risk factors, and of ESR at the time of diagnosis. Further, OPG may be a predictor of CVD. We also identified some novel potential biomarkers for CVD in RA.
Assuntos
Artrite Reumatoide , Biomarcadores , Doenças Cardiovasculares , Interleucina-17 , Humanos , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Interleucina-17/sangue , Biomarcadores/sangue , Idoso , Adulto , Osteoprotegerina/sangue , Prognóstico , Fatores de RiscoRESUMO
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
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
AIM: To investigate the bidirectional influence between periodontitis and psoriasis, using the respective experimental models of ligature- and imiquimod-induced diseases on murine models. MATERIALS AND METHODS: Thirty-two C57/BL6J mice were randomly allocated to four experimental groups: control (P- Pso-), ligature-induced periodontitis (P+ Pso-), imiquimod-induced psoriasis (P- Pso+) and periodontitis and psoriasis (P+ Pso+). Samples (maxilla, dorsal skin and blood) were harvested immediately after death. Measures of periodontitis (distance between the cemento-enamel junction and alveolar bone crest [CEJ-ABC] and the number of osteoclasts) and psoriasis (epidermal thickness and infiltrate cell [/0.03mm2]) severity as well as systemic inflammation (IL-6, IL-17A, TNF-α) were collected. RESULTS: The P+ Pso+ group exhibited the most severe experimental periodontitis and psoriasis, with the highest values of CEJ-ABC, number of osteoclasts, epidermal thickness and infiltrate cells in the dorsal skin, as well as the highest blood cytokine concentration. The P+ Pso- group presented with higher cell infiltrate (/0.03mm2) compared to the control group (p <.05), while the P- Pso+ group showed substantially higher alveolar bone loss (CEJ-ABC) than the control group (p <.05). CONCLUSIONS: Experimental periodontitis may initiate and maintain psoriasiform skin inflammation and, vice versa, experimental psoriasis may contribute to the onset of periodontitis. In a combined model of the diseases, we propose a bidirectional association between periodontitis and psoriasis via systemic inflammation.
Assuntos
Modelos Animais de Doenças , Imiquimode , Camundongos Endogâmicos C57BL , Periodontite , Psoríase , Animais , Psoríase/complicações , Psoríase/patologia , Periodontite/complicações , Periodontite/patologia , Camundongos , Distribuição Aleatória , Masculino , Fator de Necrose Tumoral alfa/sangue , Interleucina-17/sangue , Perda do Osso Alveolar/patologia , Perda do Osso Alveolar/etiologia , Osteoclastos/patologiaRESUMO
Cystic fibrosis (CF) is a multisystemic disease in which airway obstruction, infection, and inflammation play a critical role in the pathogenesis and progression of CF lung disease. The carbohydrate-binding protein Galectin-3 is increased in several inflammatory and fibrotic diseases and has recently been forwarded as a biomarker in these diseases. We aimed to define the role of serum Galectin-3 in children with CF by comparison with healthy subjects. This is a cross-sectional, case-control study. 143 CF and 30 healthy subjects were enrolled in the study. Peripheral blood and sputum concentrations of Galectins-3, interleukin (IL)-17A, IL-8, and neutrophil elastase (NE) were determined with commercial ELISA kits. There was no significant difference between the groups in age and gender (p = 0.592, p = 0.613, respectively). Serum Galectin-3 and NE concentrations were higher in the patient group than in healthy controls (p = 0.002, p < 0.001, respectively). There were no significant differences between groups according to IL-17A and IL-8 concentrations. Serum Galectin-3 was correlated with age (r = 0.289, p < 0.001) and body mass index (BMI) (r = 0.493, p < 0.001) in children with CF. Sputum Galectin-3 levels are negatively correlated with percent predictive forced expiratory volume in 1 s (FEV1) (r = - 0.297, p = 0.029), FEV1 z-score, (r = - 0.316, p = 0.020), percent predictive forced vital capacity (FVC) (r = - 0.347, p = 0.010), and FVC z-score (r = - 0.373, p = 0.006). Conclusion: The study shows that serum Galectin-3 levels increased in clinically stable CF patients, and serum Galectin-3 response may depend on age, gender, and BMI. The sputum Galectin-3 was found to be negatively correlated with patients' lung functions. What is known: ⢠Galectin-3 is a key regulator of chronic inflammation in the lung, liver, kidney, and tumor microenvironment. What is new: ⢠Children with cystic fibrosis (CF) have higher serum Galectin-3 concentrations than healthy children. ⢠Serum Galectin-3 expression influenced by age, BMI, and gender in children with CF.
Assuntos
Biomarcadores , Fibrose Cística , Galectina 3 , Humanos , Fibrose Cística/sangue , Fibrose Cística/fisiopatologia , Masculino , Feminino , Criança , Galectina 3/sangue , Estudos Transversais , Estudos de Casos e Controles , Biomarcadores/sangue , Adolescente , Escarro/metabolismo , Escarro/química , Galectinas/sangue , Interleucina-17/sangue , Pré-Escolar , Elastase de Leucócito/sangue , Proteínas Sanguíneas/análise , Interleucina-8/sangueRESUMO
Background: Interleukin-25 (IL-25) has been proved to play a role in the pathogenesis and metastasis of Hepatocellular carcinoma (HCC), but the relationship between the level of IL-25 and the metastasis and prognosis of HCC is still not clear. This study aimed to investigate the expression of IL-25 and other potential biochemical indicators among healthy people, HBV-associated HCC patients without lung metastasis and HBV-associated HCC patients with lung metastasis. Methods: From September 2019 to November 2021, 33 HCC patients without lung metastasis, 37 HCC patients with lung metastasis and 29 healthy controls were included in the study. IL-25 and other commonly used biochemical markers were measured to establish predictors of overall survival (OS) and progression-free survival (PFS) after treatment. Results: The serum level of IL-25 was increased in HCC patients than healthy controls (p < 0.001) and HCC patients with lung metastasis had higher IL-25 level than HCC patients without metastasis (p = 0.035). Lung metastasis also indicated higher death rate (p < 0.001) by chi-square test, higher GGT level (p = 0.024) and higher AFP level (p = 0.049) by non-parametric test. Kaplan-Meier analysis demonstrated that IL-25 was negatively associated with PFS (p = 0.024). Multivariate Cox-regression analysis indicated IL-25 (p = 0.030) and GGT (p = 0.020) to be independent predictors of poorer PFS, while IL-25 showed no significant association with OS. Conclusion: The level of IL-25 was significantly associated with disease progression and lung metastasis of HBV-associated HCC. The high expression of IL-25 predicted high recurrence rate and death probability of HCC patients after treatment. Therefore, IL-25 may be an effective predictor of prognosis in HCC.
Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/sangue , Masculino , Feminino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/virologia , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Prognóstico , Adulto , China/epidemiologia , Hepatite B/complicações , Hepatite B/virologia , Interleucina-17/sangue , Idoso , População do Leste AsiáticoRESUMO
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
BACKGROUND: Obstructive sleep apnea (OSA) can be considered a chronic inflammatory disease that impacts all bodily systems, including the immune system. This study aims to assess the Th17/Treg pattern in patients with OSA and the effect of continuous positive airway pressure (CPAP) treatment. METHODS: OSA patients and healthy controls were recruited. OSA patients recommended for CPAP treatment were followed up for three months. Flow cytometry was employed to determine the proportion of Th17 and Treg cells. Real-time quantitative polymerase chain reaction (PCR) and western blotting were utilized to detect the mRNA and protein levels of receptor-related orphan receptor γt (RORγt) and forkhead/winged helix transcription factor (Foxp3), respectively, in peripheral blood mononuclear cells (PBMCs). Enzyme-linked immunosorbent assay (ELISA) was performed to measure the serum levels of interleukin-17 (IL-17), IL-6, transforming growth factor-ß1 (TGF-ß1), and hypoxia-induced factor-1α (HIF-1α). RESULTS: A total of 56 OSA patients and 40 healthy controls were recruited. The proportion of Th17 cells, Th17/Treg ratio, mRNA and protein levels of RORγt, and serum IL-17, IL-6, and HIF-1α levels were higher in OSA patients. Conversely, the proportion of Treg cells, mRNA and protein levels of Foxp3, and serum TGF-ß1 levels were decreased in OSA patients. The proportion of Th17 and Treg cells in OSA can be predicted by the apnea hypopnea index (AHI), IL-6, TGF-ß1 and, HIF-1α. 30 moderate-to-severe OSA patients were adherent to three-month CPAP treatment, with improved Th17/Treg imbalance, IL-17, IL-6, TGF-ß1, and HIF-1α levels compared to pre-treatment values. CONCLUSION: There was a Th17/Treg imbalance in OSA patients. The prediction of Th17 and Treg cell proportions in OSA can be facilitated by AHI, as well as serum IL-6, TGF-ß1, and HIF-1α levels. Furthermore, CPAP treatment can potentially improve the Th17/Treg imbalance and reduce proinflammatory cytokines in OSA patients.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Apneia Obstrutiva do Sono , Linfócitos T Reguladores , Células Th17 , Humanos , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/imunologia , Apneia Obstrutiva do Sono/sangue , Células Th17/imunologia , Masculino , Linfócitos T Reguladores/imunologia , Feminino , Pessoa de Meia-Idade , Adulto , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/sangue , Interleucina-17/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fatores de Transcrição Forkhead/sangue , Fatores de Transcrição Forkhead/genética , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/genética , Interleucina-6/sangueRESUMO
OBJECTIVE: The aims of this systematic review and meta-analysis were to produce a comprehensive survey of the serum levels of interleukins (ILs) in untreated people with endometriosis compared with people without endometriosis. DATA SOURCES: A systematic literature search of English language studies within Cinahl, Medline Complete, PubMed, and Scopus from inception to May 2023 was performed. METHODS OF STUDY SELECTION: We included studies that compared IL serum levels in people with endometriosis to those without endometriosis. Meta-analysis was performed on IL-1RA, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IL-18, IL-23, and IL-37. TABULATION, INTEGRATION, AND RESULTS: The systematic search retrieved 651 studies, of which 77 underwent a full-text review. A total of 30 studies met inclusion criteria for the meta-analysis. IL-1Ra, IL-6, and IL-37 serum levels were 2.56 (95% CI 2.20-2.92, p <.001), 1.38 (95% CI 0.58-2.17, p <.001), and 1.77 (95% CI 1.33-2.20, p <.001) standard deviations higher in the patients with endometriosis compared with patients without endometriosis while IL-23 serum levels 0.40 (95% CI -0.73 to -0.07, p = .02) standard deviations lower, respectively. CONCLUSION: There is mounting evidence that ILs, especially IL-6, may be good candidates for unique noninvasive diagnostic tools and/or treatment pathways for endometriosis.
Assuntos
Endometriose , Interleucinas , Endometriose/sangue , Humanos , Feminino , Interleucinas/sangue , Interleucina-6/sangue , Interleucina-23/sangue , Proteína Antagonista do Receptor de Interleucina 1/sangue , Interleucina-18/sangue , Interleucina-2/sangue , Interleucina-10/sangue , Interleucina-17/sangue , Interleucina-1beta/sangue , Interleucina-4/sangue , Interleucina-8/sangue , Interleucina-1/sangue , Interleucina-12/sangueRESUMO
Nontypeable Haemophilus influenzae (NTHi) is a common cause of localized respiratory tract disease and results in significant morbidity. The pathogenesis of NTHi disease begins with nasopharyngeal colonization, and therefore, the prevention of colonization represents a strategy to prevent disease. The NTHi HMW1 and HMW2 proteins are a family of conserved adhesins that are present in 75 to 80% of strains and have been demonstrated to play a critical role in colonization of the upper respiratory tract in rhesus macaques. In this study, we examined the vaccine potential of HMW1 and HMW2 using a mouse model of nasopharyngeal colonization. Immunization with HMW1 and HMW2 by either the subcutaneous or the intranasal route resulted in a strain-specific antibody response associated with agglutination of bacteria and restriction of bacterial adherence. Despite the specificity of the antibody response, immunization resulted in protection against colonization by both the parent NTHi strain and heterologous strains expressing distinct HMW1 and HMW2 proteins. Pretreatment with antibody against IL-17A eliminated protection against heterologous strains, indicating that heterologous protection is IL-17A dependent. This work demonstrates the vaccine potential of the HMW1 and HMW2 proteins and highlights the importance of IL-17A in protection against diverse NTHi strains.
Assuntos
Adesinas Bacterianas/imunologia , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/patogenicidade , Adesinas Bacterianas/genética , Testes de Aglutinação , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Aderência Bacteriana , Feminino , Infecções por Haemophilus/imunologia , Infecções por Haemophilus/prevenção & controle , Haemophilus influenzae/genética , Haemophilus influenzae/imunologia , Imunização , Interleucina-17/sangue , Camundongos Endogâmicos BALB C , Nasofaringe/microbiologiaRESUMO
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.