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Dengue is a significant health problem due to the high burden of critical infections during outbreaks. In 1997, the World Health Organization (WHO) classified dengue as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It was revised in 2009 (updated in 2015), and the new guidelines recommended classifying patients as dengue without warning signs (DNS), dengue with warning signs (DWS), and severe dengue (SD). Although the utility of the revised 2009 classification for clinical studies is accepted, for immunological studies it needs to be clarified. We determined the usefulness of the 2009 classification for pediatric studies that analyze the circulating interleukin (IL)-6 and IL-8, two inflammatory cytokines. Plasma levels of IL-6 and IL-8 were evaluated in the acute and convalescent phases by flow cytometry in children with dengue classified using the 1997 and 2009 WHO guidelines. The plasma levels of IL-6 and IL-8 were elevated during the acute and decreased during convalescence, and both cytokines served as a good marker of acute dengue illness compared to convalescence. There were no differences in the plasma level of the evaluated cytokines among children with different clinical severity with any classification, except for the IL-8, which was higher in DWS than DNS. Based on the levels of IL-8, the 2009 classification identified DWS plus SD (hospital-treated children) compared to the DNS group [area under the curve (AUC): 0.7, p = 0.028]. These results support the utility of the revised 2009 (updated in 2015) classification in studies of immune markers in pediatric dengue.
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Dengue , Interleucina-6 , Interleucina-8 , Organización Mundial de la Salud , Humanos , Dengue/inmunología , Dengue/diagnóstico , Niño , Masculino , Femenino , Interleucina-6/sangre , Preescolar , Interleucina-8/sangre , Dengue Grave/diagnóstico , Dengue Grave/inmunología , Dengue Grave/sangre , Adolescente , Índice de Severidad de la Enfermedad , Biomarcadores/sangre , Virus del Dengue/inmunología , Guías de Práctica Clínica como Asunto , Citometría de Flujo , Lactante , Citocinas/sangreRESUMEN
BACKGROUND: Cytokines play an important role in the immunopathogenesis of dental caries. A systematic review and meta-analysis was carried out with the following three objectives: 1)To deepen and discuss through a comprehensive analysis of the literature the effects of dental caries on the activity and levels of TNF-α, IL-6 and IL-8 in saliva of children and young adults, 2)To compare the levels of this cytokines in saliva of the exposure group (moderate-severe dental caries) with the control group (caries-free or mild dental caries), and 3)To determine whether the levels of these cytokines could be used as a complementary clinical diagnostic tool to assess the severity of dental caries. METHODS: The protocol followed PRISMA and Cochrane guidelines and was registered in the Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/MF74V . A digital search was performed in PubMed/MEDLINE, Cochrane, Scopus, and Google Schoolar databases from February 15th, 2012, to January 13th, 2024. The methodological validity of the selected studies was assessed using Joanna Briggs Institute (JBI) tool. A meta-analysis was performed using a random-effects model to evaluate the association between dental caries/health, and the concentration of TNF-α, IL-6 and IL-8. RESULTS: The search strategy provided a total of 126 articles, of which 15 investigations met the inclusion criteria. The total number of patients studied was 1,148, of which 743 represented the case/exposure group, and 405 represented the control group. The age of the patients ranged from 3 to 25 years. IL-6 was the most prevalent cytokine in the saliva of children and young adults with active dental caries. The meta-analysis revealed that there are significant differences between the levels of IL-6 and TNF-α in saliva of children with active dental caries compared to their control groups. CONCLUSIONS: The findings suggest that IL-6 and TNF-α levels may have potential as complementary biomarkers for assessing dental caries severity. However, further research is needed to validate these findings in larger and more diverse populations before clinical application.
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Caries Dental , Interleucina-6 , Interleucina-8 , Saliva , Factor de Necrosis Tumoral alfa , Humanos , Caries Dental/metabolismo , Saliva/química , Saliva/metabolismo , Interleucina-6/análisis , Interleucina-6/metabolismo , Interleucina-8/análisis , Interleucina-8/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/metabolismo , Niño , Adulto Joven , Adolescente , Biomarcadores/análisisRESUMEN
We sought to evaluate the effect of endodontic-causative microorganisms of primary infections on mononuclear cells such as CD14+, CD4+, CD8+, CD19+ and Tregs Foxp3+. Facultative anaerobic microorganisms were isolated from radicular conducts and peripheral blood samples, which were taken from patients with primary infections. Cellular cultures were performed with peripheral blood mononuclear cells (PBMC) with and without Actinomyces spp. and Streptococcus spp. during 48, 72, and 96 h of contact in culture (concentration 5 × 105 cells/well) in a round plate bound with 48 wells. Later, PBMC was collected for analysis by flow cytometry, with the monoclonal antibodies αCD14, αCD4, αCD8, αCD19 and αFoxp3, and acquired using an FACSCanto II cytometer. The supernatant of cellular cultures was analyzed for the quantification of inflammatory cytokines. Data analysis was performed in FlowJo v10.8.2 and FCAPArray software, and statistical analysis was performed using GraphPad v5.0. software. We observed an increase in the percentage of CD14+ cells in patients at different hours of cellular culture in the presence of both Actinomyces spp. and Streptococcus spp. microorganisms, compared to healthy controls. This study demonstrates the role played by the innate immune system in the pathogeny of endodontic primary infections, explaining the effects that generate the more common microorganisms in this oral pathology.
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Leucocitos Mononucleares , Monocitos , Humanos , Actinomyces , Citocinas/metabolismo , Interleucina-12/metabolismo , Interleucina-8/metabolismo , Leucocitos Mononucleares/metabolismo , Monocitos/metabolismo , Streptococcus/metabolismoRESUMEN
Introduction: Cardiac fibroblasts (CF) are crucial cells in damaged heart tissues, expressing TLR4, IFN-receptor and responding to lipopolysaccharide (LPS) and interferon-ß (IFN-ß) respectively. While CF interact with immune cells; however, their relationship with neutrophils remains understudied. Additionally, theimpact of LPS and IFN-ß on CF-neutrophil interaction is poorly understood. Methods: Isolated CF from adult rats were treated with LPS, with or without IFN-ß. This study examined IL-8 secretion, ICAM-1 and VCAM-1 expression, and neutrophil recruitment, as well as their effects on MMPs activity. Results: LPS triggered increased IL-8 expression and secretion, along with elevated ICAM-1 and VCAM-1 expression, all of which were blocked by TAK-242. Pre-treatment with IFN-ß countered these LPS effects. LPS treated CF showed higher neutrophil recruitment (migration and adhesion) compared to unstimulated CF, an effect prevented by IFN-ß. Ruxolitinib blocked these IFN-ß anti-inflammatory effects, implicating JAK signaling. Analysis of culture medium zymograms from CF alone, and CF-neutrophils interaction, revealed that MMP2 was mainly originated from CF, while MMP9 could come from neutrophils. LPS and IFN-ß boosted MMP2 secretion by CF. MMP9 activity in CF was low, and LPS or IFN-ß had no significant impact. Pre-treating CF with LPS, IFN-ß, or both before co-culture with neutrophils increased MMP2. Neutrophil co-culture increased MMP9 activity, with IFN-ß pre-treatment reducing MMP9 compared to unstimulated CF. Conclusion: In CF, LPS induces the secretion of IL-8 favoring neutrophils recruitment and these effects were blocked by IFN-. The results highlight that CF-neutrophil interaction appears to influence the extracellular matrix through MMPs activity modulation.
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Failure of therapeutic strategies for the management and recovery from traumatic spinal cord injury (SCI) is a serious concern. Dapsone (DDS) has been reported as a neuroprotective drug after SCI, although the phase after SC damage (acute or chronic) of its major impact on functional recovery has yet to be defined. Here, we evaluated DDS acute-phase anti-inflammatory effects and their impact on early functional recovery, one week after moderate SCI, and late functional recovery, 7 weeks thereafter. Female Wistar rats were randomly assigned to each of five experimental groups: sham group; four groups of rats with SCI, treated with DDS (0, 12.5, 25.0, and 37.5 mg/kg ip), starting 3 h after injury. Plasma levels of GRO/KC, and the number of neutrophils and macrophages in cell suspensions from tissue taken at the site of injury were measured as inflammation biomarkers. Hindlimb motor function of injured rats given DDS 12.5 and 25.0 mg/kg daily for 8 weeks was evaluated on the BBB open-field ordinal scale. Six hours after injury all DDS doses decreased GRO/KC plasma levels; 24 h after injury, neutrophil numbers decreased with DDS doses of 25.0 and 37.5 mg/kg; macrophage numbers decreased only at the 37.5 mg/kg dose. In the acute phase, functional recovery was dose-dependent. Final recovery scores were 57.5 and 106.2% above the DDS-vehicle treated control group, respectively. In conclusion, the acute phase dose-dependent anti-inflammatory effects of DDS impacted early motor function recovery affecting final recovery at the end of the study.
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Esophageal squamous cell carcinoma (ESCC) is a common type of cancer characterized by fast progression and high mortality rates, which generally implies a poor prognosis at time of diagnosis. Intricate interaction networks of cytokines produced by resident and inflammatory cells in the tumor microenvironment play crucial roles in ESCC development and metastasis, thus influencing therapy efficiency. As such, cytokines are the most prominent targets for specific therapies and prognostic parameters to predict tumor progression and aggressiveness. In this work, we examined the association between ESCC progression and the systemic levels of inflammatory cytokines to determine their usefulness as diagnostic biomarkers. We analyzed the levels of IL-1ß, IL-6, IL-8, IL-10, TNF-α e IL-12p70 in a group of 70 ESCC patients and 70 healthy individuals using Cytometric Bead Array (CBA) technology. We detected increased levels of IL-1ß, IL-6, IL-8, and IL-10 in ESCC patients compared to controls. However, multivariate analysis revealed that only IL8 was an independent prognostic factor for ESCC, as were the well-known risk factors: alcohol consumption, tobacco usage, and exposure to pesticides/insecticides. Importantly, patients with low IL-6, IL-8, TNM I/II, or those who underwent surgery had a significantly higher overall survival rate. We also studied cultured Kyse-30 and Kyse-410 cells in mice. We determined that the ESCC cell line Kyse-30 grew more aggressively than the Kyse-410 cell line. This enhanced growth was associated with the recruitment/accumulation of intratumoral polymorphonuclear leukocytes. In conclusion, our data suggest IL-8 as a valuable prognostic factor with potential as a biomarker for ESCC.
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Introduction: The pathophysiology of Chronic Rhinosinusitis is coordinated by distinct inflammatory reactions in different individuals. Inflammatory environments with a predominance of Th2 lymphocytes tend also to be rich in eosinophils. These environments are common during the formation of nasal polyps associated with aspirin intolerance, which is also marked by an increase in inflammatory mediators, especially IL-4, IL-5, and IL-13. Despite the significance of these inflammatory mediators, the relevance of IL-12 subunits' presence within eosinophilic nasal polyps, however, has been less studied. The current study aims to evaluate the presence of IL-12 subunits, IL-12p40 and IL-12p70, in eosinophilic nasal polyps and their correlations with IL-8 presence. Materials and Methods: We compared the concentrations of IL-8, IL12p40, and IL12p70 among samples of eosinophilic nasal polypoid tissue, eosinophilic nasal polypoid tissue associated with aspirin intolerance, and healthy nasal mucosa, using an indirect immunoassay (ELISA) kit. Results: When compared to healthy nasal mucosa, there was a lower concentration of IL-8 in Chronic Rhinosinusitis with Nasal Polyp (CRSwNP) tissue. Aspirin Intolerant polypoid tissue also presented a lower concentration of IL-12 subunits compared to healthy nasal mucosa. There was no significant correlation between IL-8 and IL-12 in the eosinophilic polypoid conditions. Conclusion: In CRSwNP, there is a reduction in IL-8 and IL-12 subunits compared to control, with a lack of correlation between IL-12 and IL-8. The lack of correlation can be justified by a type two inflammatory storm environment.
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ABSTRACT Objective : To determine the levels of proinflammatory cytokines around miniscrews with and without loading, used during orthodontic treatment. Material and Methods : A descriptive longitudinal study was executed with a sample of ten miniscrews inserted in patients that attended a dental clinic. Saliva and peri-implant crevicular fluid samples were taken: at baseline (T0), 24 hours after insertion (T1), 1 week after insertion (T2), 24 hours after loading (T3). The samples obtained were processed by immunoassay and read with a flow cytometer. Results : Data analysis was performed using the SPSS program version 21.0. To verify normal distribution, Kolmogorov-Smirnov test was used, followed by ANOVA to compare and determine statistical significance. Levels of inflammatory mediators in the peri-implant crevicular fluid at T1 had the following order of average values: IL-8>IL-1β >IL-6>TNF-α>IL-10>IL-12p70. Higher values were found 24 hours post-insertion. Salivary levels found were lower but the previously mentioned order was maintained. Statistically significant intergroup differences were found for IL-1β and IL-8 in the peri-implant crevicular fluid. The Scheffe post hoc test showed that there were no statistically significant differences when making an intragroup pair comparison of each mediator level in a given evaluation time. No statistically significant differences were found in saliva inter and intra-group for all the evaluated inflammatory mediators. Conclusions : The miniscrew loading did not generate an increase of the concentrations of the cytokines greater than the effect caused by the insertion per se. The highest levels of inflammatory mediators were found 24 hours post-insertion of the miniscrew.
RESUMEN Objetivo : Determinar los niveles de citocinas inflamatorias alrededor de mini-implantes con y sin carga, durante el tratamiento ortodóntico. Material y métodos : Se realizó un estudio descriptivo longitudinal con una muestra de diez mini-implantes. La toma de muestras de saliva y líquido crevicular peri-implantario fue realizada en cuatro tiempos: basal (T0), 24 horas post-inserción (T1), 1 semana post-inserción (T2), 24 horas post-carga (T3). Fueron procesadas mediante una técnica de inmunoensayo y citometría de flujo. Resultados : El análisis de los datos se realizó con el programa SPSS versión 21.0. Para verificar la distribución normal se utilizó la prueba de Kolmogorov-Smirnov, seguida de la prueba ANOVA para comparar y determinar la significancia estadística. Los niveles de mediadores inflamatorios en el líquido crevicular peri-implantario en T1 tuvieron el siguiente orden de valores promedio: IL-8> IL-1β> IL-6> TNF-α> IL-10> IL-12p70. Los valores más altos se encontraron 24 horas post-inserción. Los niveles en saliva fueron menores pero se mantuvo el orden mencionado. Se hallaron diferencias estadísticamente significativas entre grupos para IL-1β e IL-8 en el líquido crevicular peri-implantario. Posteriormente, la prueba post hoc de Scheffe demostró la ausencia de diferencias estadísticamente significativas en la comparación de pares intragrupo de cada mediador. No se encontraron diferencias estadísticamente significativas inter e intragrupo para todos los mediadores inflamatorios evaluados en saliva. Conclusiones : La carga del mini-implante no generó un aumento en la concentración de citocinas mayor que el provocado por la inserción per se. Los niveles más altos se encontraron 24 horas después de la inserción.
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This study aimed to evaluate the protective function of probiotics against Shigella sonnei pathogenicity. For this purpose, 400 zebrafish were divided into four groups with two replications: (T1): receiving Lacticaseibacillus casei for 27 days, (T2): receiving L. casei for 27 days followed by 72 hr exposure to S. sonnei, (T3): receiving basal diet for 27 days followed by 72 hr exposure to S. sonnei, and control group (C): receiving basal diet without exposure to the pathogen. According to the results, feeding with L. casei for 27 days reduced the interleukin-8 (IL-8) expression significantly (P<0.05). The results showed a decrease in IL-8 expression in the group exposed to the pathogen and fed with the probiotic compared to the group only fed with the basal diet (P<0.05). Considering the role of IL-8 as a pro-inflammatory cytokine, our results indicated that feeding with L. casei could modulate inflammatory responses.
Este estudo teve como objetivo avaliar a função protetora dos probióticos contra a patogenicidade Shigella sonnei. Para este fim, 400 zebrafish foram divididos em quatro grupos com duas réplicas: (T1): recebendo Lacticaseibacillus casei por 27 dias, (T2): recebendo L. casei por 27 dias seguido por 72 horas de exposição a S. sonnei, (T3): recebendo dieta basal por 27 dias seguido por 72 horas de exposição a S. sonnei, e grupo controle (C): recebendo dieta basal sem exposição ao patógeno. De acordo com os resultados, a alimentação com L. casei por 27 dias reduziu significativamente a expressão da interleucina-8 (IL-8) (P<0,05). Os resultados mostraram uma diminuição na expressão de IL-8 no grupo exposto ao patógeno e alimentado com o probiótico em comparação com o grupo alimentado apenas com a dieta basal (P<0,05). Considerando o papel da IL-8 como uma citocina pró-inflamatória, nossos resultados indicaram que a alimentação com L. casei poderia modular as respostas inflamatórias.
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Animales , Shigella sonnei/patogenicidad , Pez Cebra , Lacticaseibacillus casei , Interleucina-8 , Alimentación AnimalRESUMEN
Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.
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Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor ß1 (TGF-ß1). Methods A total of 74 subjects were divided in the following groups: control group ( n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group ( n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group ( n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-ß1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-ß1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-ß1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.
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Abstract Introduction: In this study, we aimed to detect the cytokine that is involved in the early stage of chronic kidney disease and associated with cardiovascular disease. Methods: We included 50 patients who were diagnosed with predialytic chronic kidney disease and 30 healthy pediatric patients in Ege University Medical Faculty Pediatric Clinic, İzmir/Turkey. Interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-13 (IL-13), and transforming grow factor-β1 (TGF-β1) levels (pg/mL) were measured by ELISA. Carotid-femoral pulse wave velocity (PWV), augmentation index (Aix), carotid intima media thickness (cIMT), and left ventricular mass index (LVMI) were evaluated as markers of cardiovascular disease. The presence of a cardiovascular disease marker was defined as an abnormality in any of the parameters (cIMT, PWV, Aix, and left ventricular mass index (SVKI)). The patient group was divided into two groups as with and without cardiovascular disease. Results: Mean Aix and PWV values were higher in CKD patients than controls (Aix: CKD 32.8±11.11%, healthy subjects: 6.74±6.58%, PWV CKD: 7.31±4.34m/s, healthy subjects: 3.42±3.01m/s, respectively; p=0.02, p=0.03). The serum IL-8 levels of CKD were significantly higher than of healthy subjects 568.48±487.35pg/mL, 33.67±47.47pg/mL, respectively (p<0.001). There was no statistically significant difference between IL-8, IL-10, IL-13, TGF-1, in CKD patients with and without cardiovascular disease (p> 0.05). Discussion: IL-8 is the sole cytokine that increases in pediatric patients with chronic kidney disease among other cytokines (IL-10, IL-13 and TGF-β1). However, we did not show that IL-8 is related to the presence of cardiovascular disease.
Resumo Introdução: Neste estudo, o objetivo foi detectar a citocina envolvida no estágio inicial da doença renal crônica e associada à doença cardiovascular. Métodos: Incluímos 50 pacientes diagnosticados com doença renal crônica pré-dialítica e 30 pacientes pediátricos saudáveis na Clínica Pediátrica da Faculdade de Medicina, Universidade de Ege, İzmir/Turquia. Níveis de interleucina-8 (IL-8), interleucina-10 (IL-10), interleucina-13 (IL-13), fator de transformação do crescimento -β1 (TGF-β1) (pg/mL) foram medidos por ELISA. Velocidade de onda de pulso carotídeo-femoral (VOP), índice de amplificação (AIx), espessura da camada íntima-média da carótida (cIMT), índice de massa do ventrículo esquerdo (IMVE) foram avaliados como marcadores de doença cardiovascular. A presença de marcador de doença cardiovascular foi definida como uma anormalidade em qualquer dos parâmetros (cIMT, VOP, AIx, índice de massa do ventrículo esquerdo (IMVE)). Os pacientes foram divididos em dois grupos como com e sem doença cardiovascular. Resultados: Valores médios de AIx e VOP foram maiores em pacientes com DRC que nos controles (AIx: DRC: 32,8±11,11%, indivíduos saudáveis: 6,74±6,58%, VOP: DRC: 7,31±4,34m/s, indivíduos saudáveis: 3,42±3,01m/s, respectivamente; p=0,02, p=0,03). Níveis séricos de IL-8 de DRC foram significativamente maiores que de indivíduos saudáveis 568,48±487,35pg/mL, 33,67±47,47pg/mL, respectivamente (p<0,001). Não houve diferença estatisticamente significativa entre IL-8, IL-10, IL-13, TGF-1, em pacientes com DRC com e sem doença cardiovascular (p> 0,05). Discussão: IL-8 é a única citocina que aumenta em pacientes pediátricos com doença renal crônica entre outras citocinas (IL-10, IL-13 e TGF-β1). Entretanto, IL-8 não se associou à presença de doença cardiovascular.
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Humanos , Niño , Enfermedades Cardiovasculares , Insuficiencia Renal Crónica/complicaciones , Interleucina-8 , Grosor Intima-Media Carotídeo , Análisis de la Onda del PulsoRESUMEN
The new SARS-CoV-2 virus differs from the pandemic Influenza A virus H1N1 subtype (H1N1pmd09) how it induces a pro-inflammatory response in infected patients. This study aims to evaluate the involvement of SNPs and tissue expression of IL-17A and the neutrophils recruitment in post-mortem lung samples from patients who died of severe forms of COVID-19 comparing to those who died by H1N1pdm09. Twenty lung samples from patients SARS-CoV-2 infected (COVID-19 group) and 10 lung samples from adults who died from a severe respiratory H1N1pdm09 infection (H1N1 group) were tested. The tissue expression of IL-8/IL-17A was identified by immunohistochemistry, and hematoxylin and eosin (H&E) stain slides were used for neutrophil scoring. DNA was extracted from paraffin blocks, and genotyping was done in real time-PCR for two IL17A target polymorphisms. Tissue expression increasing of IL-8/IL-17A and a higher number of neutrophils were identified in samples from the H1N1 group compared to the COVID-19 group. The distribution of genotype frequencies in the IL17A gene was not statistically significant between groups. However, the G allele (GG and GA) of rs3819025 was correlated with higher tissue expression of IL-17A in the COVID-19 group. SARS-CoV-2 virus evokes an exacerbated response of the host's immune system but differs from that observed in the H1N1pdm09 infection since the IL-8/IL-17A tissue expression, and lung neutrophilic recruitment may be decreased. In SNP rs3819025 (G/A), the G allele may be considered a risk allele in the patients who died for COVID-19.
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COVID-19 , Regulación de la Expresión Génica/inmunología , Interleucina-17 , Interleucina-8 , Pulmón/inmunología , Neutrófilos/inmunología , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/genética , COVID-19/inmunología , COVID-19/patología , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/genética , Gripe Humana/inmunología , Interleucina-17/genética , Interleucina-17/inmunología , Interleucina-8/genética , Interleucina-8/inmunología , Pulmón/patología , Pulmón/virología , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Neutrófilos/virología , SARS-CoV-2/genética , SARS-CoV-2/inmunologíaRESUMEN
Among COVID-19 hospitalized patients, high incidence of alterations in inflammatory and coagulation biomarkers correlates with a poor prognosis. Comorbidities such as chronic degenerative diseases are frequently associated with complications in COVID-19 patients. The aim of this study was to evaluate inflammatory and procoagulant biomarkers in COVID-19 patients from a public hospital in Mexico. Blood was sampled within the first 48 h after admission in 119 confirmed COVID-19 patients that were classified in 3 groups according to oxygen demand, evolution and the severity of the disease as follows: 1) Non severe: nasal cannula or oxygen mask; 2) Severe: high flow nasal cannula and 3) Death: mechanical ventilation eventually leading to fatal outcome. Blood samples from 20 healthy donors were included as a Control Group. Analysis of inflammatory and coagulation biomarkers including D-dimer, interleukin 6, interleukin 8, PAI-1, P-selectin and VWF was performed in plasma. Routine laboratory and clinical biomarkers were also included and compared among groups. Concentrations of D-dimer (14.5 ± 13.8 µg/ml) and PAI-1 (1223 ± 889.6 ng/ml) were significantly elevated in severe COVID-19 patients (P < 0.0001). A significant difference was found in interleukin-6, PAI-1 and P-selectin in non-severe and healthy donors when compared to Severe COVID-19 and deceased patients (P < 0.001). VWF levels were also significantly different between severe patients (153.5 ± 24.3 UI/dl) and non-severe ones (133.9 ± 20.2 UI/dl) (P < 0.0001). WBC and glucose levels were also significantly elevated in patients with Severe COVID-19. Plasma concentrations of all prothrombotic biomarkers were significantly higher in patients with a fatal outcome.
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Biomarcadores/sangre , COVID-19/sangre , Mediadores de Inflamación/sangre , SARS-CoV-2 , Adulto , Anciano , COVID-19/complicaciones , COVID-19/epidemiología , Estudios de Casos y Controles , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Hospitalización , Humanos , Interleucina-6/sangre , Masculino , México/epidemiología , Persona de Mediana Edad , Selectina-P/sangre , Pandemias , Inhibidor 1 de Activador Plasminogénico/sangre , Pronóstico , Índice de Severidad de la Enfermedad , Trombosis/sangre , Trombosis/etiología , Factor de von Willebrand/metabolismoRESUMEN
Lactobacilli species are an effective biotherapeutic alternative against bacterial infections and intestinal inflammatory disorders. However, it is important to evaluate their beneficial properties, before considering them as probiotics for medical use. In this study we evaluated some probiotic properties of Lactobacillus rhamnosus GG, Lactobacillus rhamnosus KLSD, Lactobacillus helveticus IMAU70129, and Lactobacillus casei IMAU60214 previously isolated from dairy products and as control Lactobacillus casei Shirota. Experimental evaluations revealed that all strains expressed hydrophobicity (25-40%), auto-aggregation (55-60%), NaCl tolerance (1-4%), adhesion to Caco-2 cells (25-33%), partial inhibition on adherence of Escherichia coli ATCC 35218, Salmonella Typhimurium ATCC 14028, and Staphylococcus aureus ATCC 23219. Cell-free supernatants (CFS) of Lactobacilli also inhibit growth of these pathogens. In immunomodulatory properties a reduction of interleukin-8 (IL-8) and nitric oxide (NO) release was observed in assays with Caco-2 cells stimulated with interleukin-1ß (1 ng/mL), or lipopolysaccharide (0.1 µg/mL). On the other hand, the damage induced to Caco-2 cells with sodium dodecyl sulfate (SDS) was attenuated when the cultured cells were pretreated with L. rhamnosus KLDS, L. helveticus IMAU70129 and L. casei IMAU60214. These Lactobacilli possess probiotic properties determined by both an antagonistic activity on pathogenic bacteria and reduction in the inflammatory response of cells treated with SDS, a pro-inflammatory stimulant.
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There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 (p = 0.014) and AA genotypes of rs4073 IL-8 (p = 0.002), as well as high levels of IL-6 (p = 0.009) and IL-8 (p = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.
RESUMEN
The interleukin-8 is an important regulator of the tumor microenvironment, promoting the epithelial-mesenchymal transition and the acquisition of stem-like cell properties in cancer cells. The tumorsphere-formation assay has been used for the identification of cancer stem cell. Interleukin-8 induces the formation of larger tumorspheres in Michigan Cancer Foundation-7 (MCF-7) cells, suggesting cancer stem cell enrichment. In this work, we aimed to study the phenotypic and functional characteristics of the cells present within the tumorspheres of MCF-7 cells previously treated with interleukin-8. MCF-7 cells treated for 5 days or not with this cytokine were further cultivated in ultralow attachment plates for another 5 days to allow tumorspheres formation. We showed that the enhanced sphere formation by MCF-7 cells was not a consequence of higher cell proliferation by interleukin-8 stimulation. Despite maintaining an epithelial-mesenchymal transition phenotype with the presence of epithelial and mesenchymal markers, basic stemness properties were impaired in tumorspheres and in those treated with interleukin-8, while others were increased. Self-renewal capacity was increased in interleukin-8-treated cells only in the first generation of tumorspheres but was not sustained in consecutive assays. Accordingly, self-renewal and reprogramming gene expression, differentiation capacity to adipocytes, and clonogenicity were also impaired. We showed also that tumorspheres were enriched in differentiated luminal cells (EpCAM+/CD49f-). Nevertheless, cells were more quiescent and maintain a partial epithelial-mesenchymal transition, consistent with their increased resistance to Paclitaxel and Doxorubicin. They also presented higher migration and interleukin-8-directed invasion. Therefore, the breast cancer cell line MCF-7, having a low stemness index, might partially acquire some stem-like cell attributes after interleukin-8 stimulation, increasing its aggressiveness.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Interleucina-8/farmacología , Células Madre Neoplásicas/patología , Esferoides Celulares/patología , Apoptosis , Neoplasias de la Mama/patología , Proliferación Celular , Femenino , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Esferoides Celulares/efectos de los fármacos , Células Tumorales CultivadasRESUMEN
Acute ruminal acidosis (ARA) is caused by the excessive intake of highly fermentable carbohydrates, followed by the massive production of D-lactate and the appearance of neutrophilic aseptic polysynovitis. Bovines with ARA develop different lesions, such as ruminitis, polioencephalomalacia (calves), liver abscess and lameness. Lameness in cattle with ARA is closely associated with the presence of laminitis and polysynovitis. However, despite decades of research in bovine lameness as consequence of ruminal acidosis, the aetiology and pathogenesis remain unclear. Fibroblast-like synoviocytes (FLSs) are components of synovial tissue, and under pathological conditions, FLSs increase cytokine production, aggravating inflammatory responses. We hypothesized that D-lactate could induce cytokine production in bovine FLSs. Analysis by qRT-PCR and ELISA revealed that D-lactate, but not L-lactate, increased the expression of IL-6 and IL-8 in a monocarboxylate transporter-1-dependent manner. In addition, we observed that the inhibition of the p38, ERK1/2, PI3K/Akt, and NF-κB pathways reduced the production of IL-8 and IL-6. In conclusion, our results suggest that D-lactate induces an inflammatory response; this study contributes to the literature by revealing a potential key role of D-lactate in the polysynovitis of cattle with ARA.
RESUMEN
BACKGROUND: Differentiation syndrome (DS) is the main life-threatening adverse event that occurs in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA). Cytokine imbalances have been reported to play role during the developing of acute promyelocytic leukemia differentiation syndrome (APL-DS). However, the relationship between the plasma cytokine levels and their prognostic value for the prediction of DS developing in patients with APL during the treatment with ATRA and anthracyclines has not been previously reported. METHODS: In this study, we followed an APL cohort (n = 17) over 7 days of ATRA therapy in DS (n = 6) and non-DS groups (n = 11). Interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were measured in the peripheral blood plasma from 17 patients with APL and 11 healthy adult controls by using the cytometric bead array method. RESULTS: In non-DS patients, IL-8 plasma levels were significantly reduced in the seventh day of ATRA treatment (34.16; 6.99 to 147.11 pg mL- 1 in D0 vs. 10.9; 0 to 26.81 pg mL- 1 in D7; p = 0.02) whereas their levels did not discriminate between DS and non-DS development during the entire induction period (all p > 0.05 in D0, D3, and D7). No significant differences were found in IL-6 levels between groups (p > 0.05 in D0-D7). Other cytokines tested were all undetectable in patients with APL or healthy controls. CONCLUSIONS: We demonstrated that the modulation of IL-8 following ATRA treatment may occur regardless of the development of DS and, therefore, does not appear to be a predictive biomarker to monitor the APL-DS.