RESUMEN

Type 2 diabetes mellitus is a metabolic disorder that causes chronic high blood sugar levels, and diabetic patients are more susceptible to infections. American cutaneous leishmaniasis is an infectious disease caused by a parasite that affects the skin and mucous membranes, leading to one or multiple ulcerative lesions. Chronic inflammation and functional changes in various organs and systems, including the immune system, are the primary causes of both diseases. Melatonin, an essential immunomodulatory, antioxidant, and neuroprotective agent, can benefit many immunological processes and infectious diseases, including leishmaniasis. Although, limited reports are available on diabetic patients with leishmaniasis. The literature suggests that melatonin may play a promising role in inflammatory disorders. This study was designed to assess melatonin levels and inflammatory mediators in diabetic patients affected by leishmaniasis. Blood samples from 25 individuals were analyzed and divided into four groups: a control group (without any diseases), a Leishmania-positive group, patients with type 2 diabetes mellitus, and patients with a combination of both diseases. This study measured the serum levels of melatonin through ELISA, while IL-4 and TNF-α were measured using flow cytometry, and C-reactive protein was measured through turbidimetry. This study found that patients with leishmaniasis significantly increased TNF-α and decreased melatonin levels. However, the group of diabetic patients with leishmaniasis showed higher melatonin levels than the control group. These observations suggest that TNF-α may influence melatonin production in patients with American cutaneous leishmaniasis, potentially contributing to the inflammatory characteristics of both diseases.

Asunto(s)

Diabetes Mellitus Tipo 2 , Hiperglucemia , Inflamación , Melatonina , Factor de Necrosis Tumoral alfa , Melatonina/sangre , Melatonina/metabolismo , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/inmunología , Masculino , Femenino , Persona de Mediana Edad , Hiperglucemia/metabolismo , Hiperglucemia/sangre , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Inflamación/metabolismo , Inflamación/sangre , Adulto , Interleucina-4/sangre , Leishmaniasis Cutánea/sangre , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/metabolismo , Proteína C-Reactiva/metabolismo , Leishmaniasis/sangre , Leishmaniasis/inmunología , Leishmaniasis/metabolismo , Leishmaniasis/parasitología , Anciano

RESUMEN

The IgG response against SARS-CoV-2 infection can persist for over six months (long response; LR). However, among 30% of those infected, the duration can be as short as three months or less (short response; SR). The present study assembled serological data on the anti-SARS-CoV-2 IgG response duration of two previous studies and integrated these results with the plasmatic cytokine levels and genetic profile of 10 immune-relevant SNPs that were also previously published, along with the plasmatic total IgG, IgA, and IgM levels, allowing for the genetic, clinical, immunological, and epidemiological aspects of the post-COVID-19 IgG response duration to be understood. The SR was associated with previous mild acute COVID-19 and with an SNP (rs2228145) in IL6R related to low gene expression. Additionally, among the SR subgroup, no statistically significant Spearman correlations were observed between the plasma levels of IL-17A and the Th17 regulatory cytokines IFN-γ (rs = 0.2399; p = 0.1043), IL-4 (rs = 0.0273; p = 0.8554), and IL-2 (rs = 0.2204; p = 0.1365), while among the LR subgroup, weaker but statistically significant Spearman correlations were observed between the plasma levels of IL-17A and IFN-γ (rs = 0.3873; p = 0.0016), IL-4 (rs = 0.2671; p = 0.0328), and IL-2 (rs = 0.3959; p = 0.0012). These results suggest that the Th17 response mediated by the IL-6 pathway has a role in the prolonged IgG response to SARS-CoV-2 infection.

Asunto(s)

Anticuerpos Antivirales , COVID-19 , Inmunoglobulina G , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/epidemiología , COVID-19/sangre , COVID-19/virología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Masculino , Femenino , Receptores de Interleucina-6/genética , Persona de Mediana Edad , Adulto , Interleucina-17/sangre , Interleucina-17/genética , Citocinas/sangre , Inmunoglobulina A/sangre , Interferón gamma/sangre , Interferón gamma/genética , Inmunoglobulina M/sangre , Interleucina-4/sangre , Interleucina-4/genética , Anciano

RESUMEN

The parameters of the cytokine profile and functional activity of the complement system in the blood of rats were studied during different time periods of chronic unpredictable mild stress using a model of sequentially alternating low-intensity stress effects for 1, 2, 3, and 4 weeks. In the dynamics of observation, a general tendency towards multidirectional fluctuations in the concentration of cytokines was revealed: an increase in IL-10, but a decrease in IL-4 in comparison with the control. Statistically significant changes in the level of IL-10 were noted after 2, 3, and 4 weeks, IL-4 - after 2 and 4 weeks of stress loads. The percentage of lysis of the C3 component in rats gradually increased by the 2nd week of chronic stress, but then decreased and practically did not differ from the control values (intact animals) by the end of the study. These results illustrate the specificity of changes in the indicators of the C component of the complement system and the cytokine profile of the blood reflecting activity of the cellular and humoral components of the immune response in rats exposed to repeated stress factors of different origins and duration.

Asunto(s)

Complemento C3 , Interleucina-10 , Interleucina-4 , Estrés Psicológico , Animales , Ratas , Complemento C3/metabolismo , Masculino , Interleucina-10/sangre , Interleucina-4/sangre , Estrés Psicológico/sangre , Estrés Psicológico/inmunología , Ratas Wistar , Citocinas/sangre , Estrés Fisiológico/inmunología

RESUMEN

In studies investigating the etiology and pathophysiology of autism spectrum disorder (ASD), immune dysregulation is commonly observed, with elevated levels of inflammatory cytokines frequently found in gestational tissues. However, studies investigating the relationship between early immune dysregulation within the umbilical cord blood (CB) compartment and neurodevelopmental outcomes remains limited. In this exploratory study, we utilized data from the prospective Markers for Autism Risk in Babies - Learning Early Signs (MARBLES) study to examine cytokine levels in the plasma fraction of CB in infants later diagnosed with ASD (n = 38) compared to infants typically developing (TD) at age 3 years (n = 103), using multiplex cytokine assays. Our findings reveal altered levels of several inflammatory cytokines in children later diagnosed with ASD, including increased granulocyte colony-stimulating factor (G-CSF) and decreased interleukin-1α (IL-1α), IL-1ß, and IL-4 in CB. Furthermore, we identified several associations between behaviors and levels of cytokines, chemokines and growth factors. IL-1α, IL-17A, interferon γ-induced protein 10 (IP-10), and epidermal growth factor (EGF) were associated with worse scores on Autism Diagnostic Observation Schedule (ADOS) and the Mullen Scales of Early Learning (MSEL) assessments. In summary, our study demonstrates dysregulated levels of inflammatory cytokine mediators in the CB of children later diagnosed with ASD and that inflammatory mediators were associated with ASD severity, comorbid behaviors, and neurodevelopmental measures. These findings have important implications for the possible predictive value of early cytokine measures in neurodevelopmental outcomes and subsequent behavioral manifestations.

Asunto(s)

Trastorno del Espectro Autista , Citocinas , Sangre Fetal , Humanos , Trastorno del Espectro Autista/sangre , Trastorno del Espectro Autista/inmunología , Sangre Fetal/metabolismo , Femenino , Masculino , Citocinas/sangre , Preescolar , Estudios Prospectivos , Lactante , Interleucina-1alfa/sangre , Factor Estimulante de Colonias de Granulocitos/sangre , Interleucina-1beta/sangre , Interleucina-4/sangre , Interleucina-17/sangre , Factor de Crecimiento Epidérmico/sangre

RESUMEN

Behcet's syndrome (BS) is a vasculitis characterized by immune dysregulation. Biomarkers are valuable for assessing clinically atypical pathogenesis. We aimed to investigate the distribution of different biomarkers and their effects on the clinical features of patients with BS in a large-scale, real-world study. This is a retrospective, single-center study. In total, 502 patients diagnosed with BS were enrolled in this study. We analyzed the clinical features of this cohort and divided patients' symptoms into six categories, including mucocutaneous, articular, neurological, gastrointestinal, vascular, and ocular involvements. HLA-B51 cells, autoantibodies, and subsets of immune cells from the patients were tested. Pearson's correlation, Wilcoxon rank sum test and multivariate logistic regression were used for data analysis. Various autoantibodies were detected in the serum of 40.8% of patients with BS. The positivity rate of anti-endothelial cell antibodies (AECA) was the highest among autoantibodies and was found in 23.5% (118/502) of patients with BS. The positivity rate of HLA-B51 in patients with BS was 27.1%. Tumor necrosis factor (TNF)-α, IL-2, and IL-4 producing CD4+ T cells were positively correlated with the gastrointestinal BS. Increased IL-4+CD4+ T cell was a risk factor for gastrointestinal BS (P = 0.006, Overall rate [OR] = 2.491, 95% Confidence interval [CI]: [1.317, 5.100]). Various autoantibodies can be detected in patients with BS. HLA-B51 and AECA are the most common biomarkers. Increased IL-4+ CD4+ T cell was a risk factor for gastrointestinal involvement in BS.

Asunto(s)

Autoanticuerpos , Síndrome de Behçet , Biomarcadores , Humanos , Síndrome de Behçet/sangre , Síndrome de Behçet/inmunología , Síndrome de Behçet/diagnóstico , Masculino , Femenino , Adulto , Biomarcadores/sangre , Estudios Retrospectivos , Autoanticuerpos/sangre , Persona de Mediana Edad , Antígeno HLA-B51/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto Joven , Linfocitos T CD4-Positivos/inmunología , Interleucina-4/sangre

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 adversos

RESUMEN

BACKGROUND: Many studies have reported that prenatal exposure to Per- and Polyfluoroalkyl Substances (PFASs) can disrupt immune function. However, little is known about the effects of PFASs on immune molecules. The study analyzed the association between prenatal exposure to mixed and single PFASs and plasma immune molecules in three-year-old children. METHODS: Ten PFASs were measured in umbilical cord serum, while peripheral blood samples were collected at age three to measure immune molecules. Associations between exposure to individual and combined PFASs and immune molecules were analyzed using Generalized Linear Models and Weighted Quantile Sum (WQS) regression. RESULTS: (1) Interleukin-4 (IL-4) increased by 23.85% (95% CI:2.99,48.94) with each doubling of Perfluorooctanoic Acid (PFOA), and Interleukin-6 (IL-6) increased by 39.07% (95%CI:4.06,85.86) with Perfluorotridecanoic Acid (PFTrDA). Elevated PFOA and Perfluorononanoic Acid (PFNA) were correlated with increases of 34.06% (95% CI: 6.41, 70.28) and 24.41% (95% CI: 0.99, 53.27) in Eotaxin-3, respectively. Additionally, the doubling of Perfluorohexane Sulfonic Acid (PFHxS) was associated with a 9.51% decrease in Periostin (95% CI: -17.84, -0.33). (2) The WQS analysis revealed that mixed PFASs were associated with increased IL-6 (ß = 0.37, 95%CI:0.04,0.69), mainly driven by PFTrDA, PFNA, and 8:2 Chlorinated Perfluoroethyl Sulfonamide (8:2 Cl-PFESA). Moreover, mixed PFASs were linked to an increase in Eotaxin-3 (ß = 0.32, 95% CI: 0.09,0.55), primarily influenced by PFOA, PFTrDA, and Perfluorododecanoic Acid (PFDoDA). CONCLUSIONS: Prenatal PFASs exposure significantly alters the levels of immune molecules in three-year-old children, highlighting the importance of understanding environmental impacts on early immune development.

Asunto(s)

Fluorocarburos , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Fluorocarburos/sangre , Fluorocarburos/toxicidad , Preescolar , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , China/epidemiología , Masculino , Contaminantes Ambientales/sangre , Sangre Fetal/inmunología , Sangre Fetal/química , Caprilatos/sangre , Caprilatos/toxicidad , Interleucina-6/sangre , Interleucina-4/sangre , Ácidos Decanoicos/sangre , Ácidos Decanoicos/toxicidad , Ácidos Alcanesulfónicos/sangre , Ácidos Alcanesulfónicos/toxicidad , Adulto , Exposición Materna/efectos adversos

RESUMEN

OBJECTIVE: To investigate the levels of 12 kinds of cytokines in seminal plasma and their correlations with routine semen parameters. METHODS: The remaining seminal plasma samples of 134 patients undergoing routine semen examination were collected for detecting cytokines. The parameters for sperm concentration, percentage of progressively motile sperm (PR), and motility were analyzed by a computer-assisted sperm analysis (CASA) system. According to the results of sperm concentration, PR and motility, 134 patients were divided into the normal routine semen parameters group, oligoasthenospermia group and azoospermia group. The levels of 12 kinds of cytokines in seminal plasma, including interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferin (IFN)-α, IFN-γ, and tumor necrosis factor (TNF)-α, were detected by flow cytometry. Two seminal plasma samples were detected for 10 times, respectively, to calculate the coefficients of variation (CV) of each cytokine. The linear range of each cytokine was measured using the standard, and the correlation coefficient (r) was calculated. RESULTS: The r2 of 12 kinds of cytokines detected by flow cytometry were all greater than 0.99. The reproducibility of 2 seminal plasma samples showed that the CVs of all cytokines were lower than 15 % except for TNF-α in sample 1 (15.15 %). Seminal plasma IL-6 levels were negatively correlated with semen volume (P < 0.01). Seminal plasma IL-5 levels were positively correlated with sperm concentration (P < 0.01). Seminal plasma IL-8 levels were negatively correlated with sperm motility (P < 0.01). Seminal plasma IL-8, IL-17 and IL-12P70 levels were negatively correlated with sperm PR (P < 0.05). In addition to the significant negative correlation between IL-5 and IL-17 (P < 0.05), there was a significant positive correlation between the majority of other cytokines. The levels of seminal plasma IL-17 and IL-12P70 in the oligoasthenospermia group and IL-1ß and IL-12P70 in the azoospermia group were significantly higher than those in the normal routine semen parameters group (P ≤ 0.05), while the levels of IL-10 in the azoospermia group were significantly lower than that in the normal routine semen parameters group (P < 0.05). CONCLUSION: There are certain correlations between seminal plasma cytokines and routine semen parameters and strong correlations between different seminal plasma cytokines, suggesting that the imbalance between seminal plasma cytokines may affect sperm quality. However, it still needs to be further confirmed by large samples and multi-center clinical studies and related basic researches.

Asunto(s)

Citocinas , Citometría de Flujo , Análisis de Semen , Semen , Motilidad Espermática , Humanos , Masculino , Semen/metabolismo , Adulto , Citocinas/sangre , Citocinas/metabolismo , Citometría de Flujo/métodos , Análisis de Semen/métodos , Interleucina-5/metabolismo , Interleucina-5/sangre , Interleucina-17/sangre , Interleucina-17/metabolismo , Interleucina-17/análisis , Recuento de Espermatozoides , Interleucina-6/sangre , Interleucina-6/análisis , Interleucina-6/metabolismo , Interleucina-8/sangre , Interleucina-8/metabolismo , Interleucina-8/análisis , Interleucina-12/sangre , Interleucina-12/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/análisis , Interferón gamma/sangre , Interferón gamma/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/sangre , Interleucina-1beta/análisis , Interleucina-10/sangre , Interleucina-10/metabolismo , Interleucina-10/análisis , Azoospermia/metabolismo , Azoospermia/sangre , Interleucina-2/sangre , Interleucina-2/metabolismo , Interleucina-2/análisis , Interleucina-4/sangre , Interleucina-4/metabolismo , Interleucina-4/análisis , Oligospermia/metabolismo

RESUMEN

BACKGROUND: Long non-coding RNAs (lncRNAs) play various roles in gene regulation. GATA3 antisense RNA 1 (GATA3-AS1) is an lncRNA gene neighboring GATA binding protein 3 (GATA3). The current study aims to quantitatively compare the levels of the expression of GATA3-AS1, GATA3, and Interleukin-4 (IL-4) in peripheral blood mononuclear cells (PBMC) samples of MS patients and healthy individuals under the hypothesis of regulation of GATA3 and IL-4 expression orchestrated by GATA3-AS1. METHODS AND RESULTS: In this case-control study, the GATA3-AS1, GATA3 and IL-4 expression profiles were assessed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Also, we assessed the IL-4 levels in the serum. The median fold changes in MS patients vs. controls were (4.39 ± 0.38 vs. 2.44 ± 0.20) for GATA3-AS1, (5.22 ± 0.51 vs. 2.86 ± 0.30) for GATA3, and (6.16 ± 0.52 vs. 3.57 ± 0.38) for IL-4, (P < 0.001). Furthermore, the mean serum levels of IL-4 were 30.85 ± 1.53 pg/ml in MS patients and 11.15 ± 4.23 pg/ml in healthy controls (P < 0.001). ROC curve analysis showed that the level of GATA3-AS1 might serve as a biomarker for diagnosing MS patients with the area under the curve (AUC = 0.918, P < 0.0001). Based on our results, this GATA3-AS1/GATA3/IL-4 pathway may increase IL-4 expression in MS patients. CONCLUSIONS: Our results indicate a probably regulatory function for GATA3-AS1and the levels of GATA3-AS1 in blood could be important biomarkers for MS diagnosis. To confirm and be more certain of these results, it is necessary to study neuromyelitis optica (NMO) and asthma patients in future studies.

Asunto(s)

Factor de Transcripción GATA3 , Interleucina-4 , Leucocitos Mononucleares , Esclerosis Múltiple , ARN Largo no Codificante , Humanos , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Interleucina-4/genética , Interleucina-4/sangre , ARN Largo no Codificante/genética , ARN Largo no Codificante/sangre , Femenino , Adulto , Masculino , Esclerosis Múltiple/genética , Esclerosis Múltiple/sangre , Esclerosis Múltiple/metabolismo , Estudios de Casos y Controles , Leucocitos Mononucleares/metabolismo , Regulación hacia Arriba/genética , Persona de Mediana Edad , Regulación de la Expresión Génica/genética , ARN sin Sentido/genética

RESUMEN

An increasing body of evidence supports the involvement of inflammation and immune responses in the occurrence and development of keratoconus (KC). However, the causal relationship between inflammatory factors and KC remains unclear. We employed a 2-way Mendelian randomization (MR) approach to investigate the interaction between KC and inflammatory factors. Instrumental variables for 41 circulating inflammatory regulators and 12 matrix metalloproteinases (MMPs) were selected from genome-wide association studies of European ancestry. Summary statistics for KC were obtained from a genome-wide association study comprising 2116 cases and 24,626 controls of European ancestry. The primary analytical method for assessing causality was the inverse-variance weighted method. Two additional MR methods (MR-Egger and weighted median) were employed to complement the inverse-variance weighted results. In addition, several sensitivity analyses were conducted to evaluate heterogeneity, horizontal pleiotropy, and stability. Our findings indicated that genetically predicted higher levels of macrophage inflammatory protein-1ß (odds ratio = 1.126, 95% confidence interval: 1.029-1.232, P = .01) and MMP-13 (odds ratio = 1.211, 95% confidence interval: 1.070-1.371, P = .003) were positively associated with an elevated risk of KC. Conversely, genetically predicted KC was associated with increased levels of interferon-gamma, interleukin-4, and MMP-1. Our current study provided suggestive evidence supporting causal associations of macrophage inflammatory protein-1ß and MMP-13 with the risk of KC. In addition, KC appeared to affect the expression of interferon-gamma, interleukin-4, and MMP-1.

Asunto(s)

Estudio de Asociación del Genoma Completo , Inflamación , Queratocono , Análisis de la Aleatorización Mendeliana , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Queratocono/genética , Queratocono/epidemiología , Inflamación/genética , Polimorfismo de Nucleótido Simple , Interleucina-4/genética , Interleucina-4/sangre , Metaloproteinasa 13 de la Matriz/genética , Predisposición Genética a la Enfermedad

RESUMEN

Coronary heart disease (CHD) is related to aberrant aggregation of immune cells in the plaques. This study focused on identification of abnormal T cell subtypes and inflammatory factors in CHD patients. To this end, the subtypes of T cells in peripheral blood of CHD patients (n=141) and healthy controls (n=46) were analyzed by flow cytometry. Plasma concentrations of cytokines were analyzed by multiplex assay. It was shown that the number of T helper cells producing granulocyte-macrophage CSF (GM-CSF) was higher in CHD patients in comparison with healthy controls. In addition, the fractions of Th1 and Th17 cells as well as the levels of IL-4, IL-5, IL-6, and IL-10 in CHD patients also surpassed the control values (p<0.05). However, the level of GM-CSF was insignificantly lower in CHD patients. Thus, we revealed a relationship between the number of T cells producing GM-CSF and the severity of CHD. Our results can be used to develop new potential biomarkers for CHD detection.

Asunto(s)

Biomarcadores , Enfermedad Coronaria , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Interleucina-6 , Humanos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Masculino , Femenino , Enfermedad Coronaria/inmunología , Enfermedad Coronaria/sangre , Persona de Mediana Edad , Biomarcadores/sangre , Interleucina-6/sangre , Estudios de Casos y Controles , Interleucina-10/sangre , Células Th17/inmunología , Células Th17/metabolismo , Células TH1/inmunología , Células TH1/metabolismo , Interleucina-4/sangre , Anciano , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Adulto , Citometría de Flujo , Interleucina-5

RESUMEN

Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience numerous complications, which are exacerbated by inflammatory dysregulation and infection. Understanding the immunological mechanisms is crucial for selecting medications that balance inflammation control and immunocompetence. In this cross-sectional study, aiming to identify potential immunotherapeutic targets and inflammatory biomarkers, we delved into the interrelationship between clinical severity and systemic inflammatory parameters in a representative RDEB cohort. Encompassing 84 patients aged 1-67 and spanning all three Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) severity categories, we analysed the interrelationship of infection history, standard inflammatory markers, systemic cytokines and Ig levels to elucidate their roles in RDEB pathophysiology. Our findings identify C-reactive protein as an excellent biomarker for disease severity in RDEB. A type 2 inflammatory profile prevails among moderate and severe RDEB patients, correlating with dysregulated circulating IgA and IgG. These results underscore the IL4/IL13 pathways as potential evidence-based therapeutic targets. Moreover, the complete inflammatory scenario aligns with Staphylococcus aureus virulence mechanisms. Concurrently, abnormalities in IgG, IgE and IgM levels suggest an immunodeficiency state in a substantial number of the cohort's patients. Our results provide new insights into the interplay of infection and immunological factors in the pathogenesis of RDEB.

Asunto(s)

Biomarcadores , Proteína C-Reactiva , Epidermólisis Ampollosa Distrófica , Interleucina-13 , Interleucina-4 , Índice de Severidad de la Enfermedad , Humanos , Estudios Transversales , Biomarcadores/sangre , Niño , Preescolar , Interleucina-4/sangre , Adolescente , Proteína C-Reactiva/metabolismo , Adulto , Adulto Joven , Femenino , Masculino , Lactante , Persona de Mediana Edad , Interleucina-13/sangre , Interleucina-13/metabolismo , Anciano

RESUMEN

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 Enfermedad

RESUMEN

Inflammation-derived oxidative stress is postulated to contribute to neuronal damage leading to poor clinical outcomes in Acute Ischemic Stroke (AIS). We aimed to investigate the association between serum levels of selected cytokines (IL-1ß, IFN-γ, IL-4), and vitamin D in ischemic stroke progression, and their accuracy in predicting AIS prognosis, among Sri Lankans. We compared 60 AIS patients admitted in 4 phases post-stroke onset (<6 h; 6-24 h; 24-48 h; 48-96 h; n = 15/phase), with 15 age- and sex-matched controls. The 30-day functional outcome (FO) was assessed using the modified Rankin Scale (mRS). Serum cytokine and vitamin D levels were quantified using sandwich ELISAs, and competitive ELISA, respectively. The CombiROC web tool established optimal prognostic biomarker combinations. Serum IL-1ß and IFN-γ were elevated in all four phases following stroke onset while IL-4 was elevated exclusively in the recovery phase (48-96 h) (p<0.05). Th1 bias polarization of the Th1:Th2 cytokine (IFN-γ:IL-4) ratio occurred with AIS progression while a Th2 bias occurred during AIS recovery (p<0.05). Lower serum IL-1ß and higher IL-4 levels were associated with a good FO (p<0.05), while lower Vitamin D levels were related to a poor FO (p = 0.001). The triple-biomarker panel, IL-4- IFN-γ -Vit D, accurately predicted AIS prognosis (sensitivity = 100%, specificity = 91.9%, area under the curve = 0.98). Serum immunologic mediators IFN-γ, IL-4, and vitamin D may be useful biomarkers of AIS prognosis and may serve as therapeutic targets in improving stroke outcomes. Vitamin D supplementation may improve the prognosis of AIS patients. Furthermore, binary logistic model fitted for FO indicated Th1:Th2 cytokine ratio (IFN-γ:IL-4), vitamin D status, history of stroke, and ischemic heart disease as significant predictors of AIS prognosis.

Asunto(s)

Biomarcadores , Citocinas , Accidente Cerebrovascular Isquémico , Vitamina D , Humanos , Femenino , Masculino , Vitamina D/sangre , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/diagnóstico , Pronóstico , Biomarcadores/sangre , Persona de Mediana Edad , Anciano , Citocinas/sangre , Interleucina-4/sangre , Interferón gamma/sangre , Estudios de Casos y Controles

RESUMEN

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 , Adolescente

RESUMEN

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).

Asunto(s)

Quimiocina CCL2 , Neoplasias Endometriales , Interleucina-17 , Interleucina-6 , Neutrófilos , Humanos , Femenino , Neutrófilos/metabolismo , Neutrófilos/inmunología , Neoplasias Endometriales/inmunología , Neoplasias Endometriales/sangre , Neoplasias Endometriales/patología , Neoplasias Endometriales/metabolismo , Interleucina-6/sangre , Quimiocina CCL2/sangre , Interleucina-17/sangre , Persona de Mediana Edad , Interleucina-4/sangre , Peroxidasa/sangre , Peroxidasa/metabolismo , Interleucina-18/sangre , Neoplasias Uterinas/sangre , Neoplasias Uterinas/inmunología , Neoplasias Uterinas/patología , Factor Estimulante de Colonias de Granulocitos/sangre , Factor Estimulante de Colonias de Granulocitos/metabolismo , Fagocitosis , Leiomioma/sangre , Leiomioma/inmunología , Leiomioma/patología , Leiomioma/metabolismo , Citocinas/sangre , Citocinas/metabolismo , Elastasa de Leucocito/sangre , Elastasa de Leucocito/metabolismo , Adulto , Trampas Extracelulares/metabolismo , Trampas Extracelulares/inmunología , Especies Reactivas de Oxígeno/metabolismo , Anciano , Interleucina-2

RESUMEN

OBJECTIVE: Aim: To study the Respiratory pathology of the upper respiratory tract, markers of the inflammatory response of the organism, Oxidative stress, Metabolic adaptation and possibilities of correction. PATIENTS AND METHODS: Materials and Methods: The study group (n=111) included school-aged children (10-14 years old). The general group of inflammatory diseases of the respiratory tract (J000-J06) was considered, with a diagnosis of acute respiratory infection (ARI) of viral and bacterial origin and included local inflammationof the upper respiratory tract with presentation of acute pharyngitis (68.0%), acute bronchitis (22,0%), acute tonsillitis (10,0%). RESULTS: Results: Dynamic observation of groups of children who received optimized (group 1, n=60) and basic (group 2, n=51) treatment was carried out. The level of the erythrocyte pool correlated with IL-1 (r=-0,29, p=0,03), IL-4 (r=0,32, p=0,01), TNF-α (r=-0,35 , p=0,006). Creatinine value correlated with IL-10 (r=0,3, p=0,005), γ-IFN (r=0,42, p=0,001), TNF-α (r=0,25, p=0,05). Correlations of ferritin presented positive correlation values with the level of total protein (r=0,26, p=0,04) and TNF-α (r=0,41, p=0,001). CONCLUSION: Conclusions: After the optimized treatment, there was a significant decrease in the reliable levels of CRP and γ-IFN by 7 and 4,4 times (by groups) and 5,8 and 3,2 times (by groups), respectively. Correlation relationships of urea levels with IL-2,4 were detected. The level of the erythrocyte pool correlated with IL-1,4, TNF-α, Ferritin presented positive correlation values with the level of total protein,TNF-α .

Asunto(s)

Infecciones del Sistema Respiratorio , Humanos , Niño , Adolescente , Masculino , Femenino , Biomarcadores/sangre , Enfermedad Aguda , Factor de Necrosis Tumoral alfa/sangre , Interleucina-4/sangre , Ferritinas/sangre , Estrés Oxidativo

RESUMEN

BACKGROUND: Aim of this study was the isolation of native probiotic and determine the effect of combination of Beta Glucan and Lactobacillus rhamnosus Heriz I on White Blood Cell Counts and serum levels of IL-4and IL-12 in breast cancer women receiving Chemotherapy. METHODS: This study was randomized double-blind placebo-controlled clinical trial in 30 women with breast cancer. Women in the intervention group received two 10-mg capsules of soluble 1-3,1-6, D-beta glucan and one capsule of Lactobacillus rhamnosus strain Heriz I (2 × 107 CFU) daily and placebo group received placebo during 21days, interval between two courses of chemotherapy. White blood cells, neuthrophil, lymphocyte and monocyte counts, serum levels of IL-4 and IL-12 were measured before and after the study. RESULTS: We isolated Lactobacillus rhamnosus Heriz I from conventional yogurt of Heriz region and registered in NCBI GeneBank. After administration, in both groups white blood cells counts decreased. At the end of study, serum level of IL-4 was decreased in combination group compared to placebo (P = 0.005). Also, serum level of IL-12 in combination group increased non-significantly (P = 0.066). CONCLUSION: The findings suggest that combination of Beta Glucan and Lactobacillus rhamnosus Heriz I may be useful as immunomodulary supplements in chemotherapy patients however further studies were needed.

Asunto(s)

Neoplasias de la Mama , Interleucina-12 , Interleucina-4 , Lacticaseibacillus rhamnosus , Probióticos , beta-Glucanos , Humanos , Femenino , Método Doble Ciego , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/sangre , Interleucina-12/sangre , Probióticos/uso terapéutico , Interleucina-4/sangre , Persona de Mediana Edad , Adulto , Recuento de Leucocitos

RESUMEN

Asthma is a chronic inflammatory disease of the airways strongly associated with interleukin-4 (IL-4), a cytokine that mediates and regulates various immune responses, including allergic reactions. This study aimed to evaluate the anti-inflammatory and antioxidant effects of an Aqueous Extract of Clove (AEC) Syzygium aromaticum on the lungs and erythrocytes of an experimental asthma model in Wistar rats. For this purpose, four groups of male rats were examined: control, sensitized with ovalbumin (OVA), treated with AEC, and treated with a combination of OVA/AEC. After treatment, the antioxidant effect was determined by measuring the malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione (GSH), and catalase (CAT) levels. The anti-inflammatory effect was determined by measuring IL-4 levels by performing enzyme-linked immunosorbent assay (ELISA) using serum, lung, and bronchoalveolar lavage fluid (BALF) samples. A significant reduction (p ≤ 0.05) in the MDA levels and a significant increase (p ≤ 0.05) in the levels of GPx and CAT were observed in the lungs of rats treated with cloves. However, no statistically significant variation was observed in GSH levels. In erythrocytes, no statistically significant differences were observed between the experimental batches. Regarding the anti-inflammatory effect, the administration of S. aromaticum extract to sensitized rats resulted in a recovery in the levels of total proteins and IL-4 and a decrease in the three compartments studied (lungs, serum, and bronchoalveolar liquid). These results were confirmed by microscopic examination of lung histological sections. Overall, these findings confirmed that the AEC has anti-inflammatory and antioxidant effects.

Asunto(s)

Antiinflamatorios , Antioxidantes , Asma , Líquido del Lavado Bronquioalveolar , Modelos Animales de Enfermedad , Glutatión Peroxidasa , Glutatión , Interleucina-4 , Pulmón , Malondialdehído , Extractos Vegetales , Ratas Wistar , Syzygium , Animales , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Syzygium/química , Masculino , Asma/tratamiento farmacológico , Asma/inducido químicamente , Asma/metabolismo , Asma/patología , Líquido del Lavado Bronquioalveolar/química , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión/metabolismo , Interleucina-4/metabolismo , Interleucina-4/sangre , Malondialdehído/metabolismo , Ovalbúmina , Catalasa/metabolismo , Ratas , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Agua/química

RESUMEN

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 , Adolescente