RESUMEN
Introduction: Chronic obstructive pulmonary disease (COPD) is associated with tobacco smoking and biomass-burning smoke exposure. Toll-like receptor 4 (TLR4) single-nucleotide polymorphisms (SNPs) may contribute to its pathogenesis. The study aimed to assess the association of rs4986790 and rs4986791 in the TLR4 gene in a Mexican mestizo population with COPD secondary to tobacco smoking (COPD-TS) and biomass-burning smoke (COPD-BBS) and to evaluate whether the genotypes of risk affect cytokine serum levels. Materials and methods: We enrolled 2,092 participants and divided them into two comparisons according to their environmental exposure. SNPs were genotyped using TaqMan probes. Serum cytokine levels (IL-4, IL-5, IL-6, IL-10, and INF-γ) were quantified by ELISA. Results: The rs4986790 AA genotype in COPD-TS was associated with a higher COPD risk (OR = 3.53). Haplotype analysis confirmed this association, identifying a block containing the rs4986790 allele (A-C, OR = 3.11). COPD-TS exhibited elevated IL-6, IL-4, and IL-5 levels compared with smokers without COPD (SWOC), whereas COPD-BBS displayed higher IFN-γ, IL-6, and IL-10 levels. The AA carriers in the COPD-TS group had elevated IL-4, IL-5, and IFN-γ compared with carriers of AG or GG. Conclusion: The rs4986790 common allele and the A-C haplotype (rs4986790-rs4986791) were associated with a higher COPD risk in smokers; COPD patients carrying the AA genotype showed increased pro-inflammatory cytokines.
Asunto(s)
Genotipo , Interferón gamma , Polimorfismo de Nucleótido Simple , Enfermedad Pulmonar Obstructiva Crónica , Receptor Toll-Like 4 , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/etiología , Masculino , Femenino , Receptor Toll-Like 4/genética , Persona de Mediana Edad , Interferón gamma/genética , Interferón gamma/sangre , Anciano , Interleucina-4/genética , Interleucina-4/sangre , Biomasa , Predisposición Genética a la Enfermedad , Interleucina-5/genética , Interleucina-5/sangre , Humo/efectos adversos , México , Adulto , Fumadores , Fumar/efectos adversosRESUMEN
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.
Asunto(s)
Asma , Citocinas , Interleucina-13 , Interleucina-4 , Leucocitos Mononucleares , Transcriptoma , Humanos , Asma/genética , Asma/sangre , Asma/inmunología , Asma/tratamiento farmacológico , Masculino , Femenino , Leucocitos Mononucleares/metabolismo , Adulto , Persona de Mediana Edad , Citocinas/genética , Citocinas/sangre , Estudios Longitudinales , Interleucina-4/genética , Interleucina-4/sangre , Interleucina-13/genética , Interleucina-13/sangre , Eosinófilos , Linfopoyetina del Estroma Tímico , Interleucina-5/genética , Interleucina-5/sangre , Interleucina-33/genética , Interleucina-33/sangre , Interleucina-17/genética , Interleucina-17/sangre , Corticoesteroides/uso terapéutico , Perfilación de la Expresión Génica/métodos , Progresión de la Enfermedad , Índice de Severidad de la EnfermedadRESUMEN
Asthma is an airways inflammatory disease and the most common chronic disease of childhood, which causes most hospital visits and placing a heavy financial burden on families and communities. Interleukins 4, 5 and 13, play a central role in the pathogenesis of asthma. Given the importance of oral hygiene in asthmatic patients and IL-4 and 5 are involved in the inflammatory process of periodontitis, the effect of chlorhexidine as mouthwash on asthma attacks in children on serum cytokines is necessary. In this study, 375 children with asthma were divided into two groups using or non-using chlorhexidine. Blood samples were taken and cytokines were measured by ELISA. From 375 patients, 17 patients were excluded. In this study, 171 males and 187 females participated and there were 180 patients in asthma group and 178 patients in asthma/Chlorhexidine group. The levels of IL-4, IL-5 and IL-13 had no significant difference (p > 0.05) between Asthma and Asthma/Chlorhexidine groups. Using chlorhexidine as mouthwash in children with asthma had no effect on the type 2 cytokines and may not trigger an asthma attack via allergo-inflammatory mechanism.
Asunto(s)
Asma , Clorhexidina , Interleucina-4 , Antisépticos Bucales , Humanos , Clorhexidina/administración & dosificación , Asma/sangre , Asma/tratamiento farmacológico , Antisépticos Bucales/administración & dosificación , Femenino , Masculino , Niño , Interleucina-4/sangre , Interleucina-13/sangre , Interleucina-5/sangre , Citocinas/sangre , Preescolar , Antiinfecciosos Locales/administración & dosificación , AdolescenteRESUMEN
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.
Asunto(s)
Citometría de Flujo , Interleucina-17 , Interleucina-2 , Interleucina-4 , Interleucina-5 , Humanos , Citometría de Flujo/métodos , Masculino , Interleucina-17/sangre , Femenino , Adulto , Interleucina-5/sangre , China , Interleucina-2/sangre , Interleucina-4/sangre , Persona de Mediana Edad , Valores de Referencia , Adulto Joven , Anciano , Voluntarios Sanos , AdolescenteRESUMEN
We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.
Asunto(s)
Animales , Femenino , Acetaminofén , Analgésicos no Narcóticos , Fallo Hepático Agudo , Teniasis/parasitología , Acetaminofén/administración & dosificación , Alanina Transaminasa/sangre , Analgésicos no Narcóticos/administración & dosificación , Biomarcadores/sangre , Citocromo P-450 CYP2E1/biosíntesis , Citocromo P-450 CYP2E1/sangre , Modelos Animales de Enfermedad , Hepatocitos/parasitología , Hepatocitos/patología , Interleucina-5/sangre , Interleucina-6/sangre , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/parasitología , Fallo Hepático Agudo/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Teniasis/patologíaRESUMEN
The protective effect of infectious agents against allergic reactions has been thoroughly investigated. Current studies have demonstrated the ability of some helminths to modulate the immune response of infected hosts. The objective of the present study was to investigate the relationship between Toxocara canis infection and the development of an allergic response in mice immunised with ovalbumin (OVA). We determined the total and differential blood and bronchoalveolar lavage fluid cells using BALB/c mice as a model. To this end, the levels of interleukin (IL)-4, IL-5 and IL-10 and anti-OVA-IgE were measured using an ELISA. The inflammatory process in the lungs was observed using histology slides stained with haematoxylin and eosin. The results showed an increase in the total number of leukocytes and eosinophils in the blood of infected and immunised animals at 18 days after infection. We observed a slight lymphocytic inflammatory infiltrate in the portal space in all infected mice. Anti-OVA-IgE levels were detected in smaller proportions in the plasma of immunised and infected mice compared with mice that were only infected. Therefore, we concluded that T. canis potentiates inflammation in the lungs in response to OVA, although anti-OVA-IgE levels suggest a potential reduction of the inflammatory process through this mechanism.
Asunto(s)
Animales , Líquido del Lavado Bronquioalveolar/parasitología , Hipersensibilidad/parasitología , Pulmón/inmunología , Toxocara canis/inmunología , Toxocariasis/inmunología , Anticuerpos/sangre , Biopsia , Ensayo de Inmunoadsorción Enzimática , Eosinófilos/parasitología , Inmunoglobulina E/sangre , Inflamación/fisiopatología , Interleucina-10/sangre , Interleucina-4/sangre , Interleucina-5/sangre , Recuento de Leucocitos , Pulmón/patología , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Toxocariasis/sangreRESUMEN
El CD23, descripto como una glucoproteína de 45 kDa, está relacionado con la activación de los linfocitos B y la regulación de la síntesis de IgE. Se degrada en fragmentos solubles (CD23s). Es una multicitocina involucrada en patologías con predominio de linfocitos TH2, tales como las enfermedades alérgicas, leucemia B crónica o en injerto de médula ósea. El 70 por ciento de los asmáticos presenta niveles de IgE aumentados. El eosinófilo es la célula central de la inflamación asmática. Objetivo: se evaluó la corrrelación entre niveles de CD23s, IgE sérica, eosinofilia sanguínea y esputo en asmáticos atópicos y por aspirina, frente a un grupo control de individuos normales. Pacientes: se estudiaron 27 pacientes atópicos: 14m, 13f, 10 asmáticos por AAS: 4m, 6f. Un grupo control de 10 sujetos: 5m, 5f. Nadie recibió corticoides en los dos meses previos. Se determinaron IgE total por ELISA Kabi-Pharmacia, CD23s por ELISA, Binding Site, MK112. Recuentos de eosinófilos en esputo y sangre periférica. Resultados: IgE:asmáticos atópicos: 500Ï252kU/l. Asmáticos por AAS: 68Ï27 kU/l. Controles: 51Ï20 kU/l<0.0005. CD23s: asmáticos atópicos: 7.65Ï2.25 ng/ml. Asmáticos por AAS: 3.4Ï0,95 ng/ml. Controles: 3.73Ï1.08 ng/ml; p<0.0005. Eosinófilos en esputo: asmáticos atópicos: 25Ï13 por ciento. Asmáticos por AAS: 23Ï13 por ciento. NS. Eosinofilia sanguínea: asmáticos atópicos: 685Ï316/mm3. Asmáticos por AAS: 555Ï190/mm3 NS. Control: 255Ï90mm3; p<0.0005. Conclusiones: nuestro estudio demuestra un incremento de la IgE y CD23s en los asmáticos atópicos. Los sensibles a aspirina no presentaron cambios significativos respecto del grupo control. La eosinofilia positiva se encontró en ambos grupos de asmáticos. Esto sugiere diferentes mecanismos inflamatorios en asma bronquial, con una vía común representada por los eosinófilos