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1.
Article in English | WPRIM | ID: wpr-921358

ABSTRACT

To explore interleukin-6 (IL-6) production and characterize lipid accumulation in L02 hepatocytes induced by sodium oleate. L02 hepatocytes were incubated with 0, 37.5, 75, 150, 300, 600, or 1,200 μmol/L sodium oleate for 24 h, and the supernatant was collected to detect the concentration of IL-6. L02 hepatocytes were incubated with 300, 150, 75, or 0 μmol/L sodium oleate for 0-24 h. The supernatant was collected for detection of IL-6 and free fatty acids. L02 hepatocytes treated with 300 μmol/L sodium oleate for 0-24 h were stained with Oil Red O. With extended sodium oleate incubation time, IL-6 levels increased, and free fatty acids decreased. After 24 h incubation, IL-6 levels increased as sodium oleate increased from 37.5 to 300 μmol/L (


Subject(s)
Dose-Response Relationship, Drug , Hepatocytes/metabolism , Humans , Interleukin-6/metabolism , Lipid Metabolism , Oleic Acid/administration & dosage , Time Factors
2.
Braz. oral res. (Online) ; 34: e013, 2020. graf
Article in English | LILACS | ID: biblio-1089379

ABSTRACT

Abstract This study evaluated the effect of a cyclopentenone-type PG, 15-Deoxy-Δ12,14-PG J2 (15d-PGJ2), and lectin (ScLL) on the viability of human gingival fibroblasts (HGFs), and on IL-6 and TGFβ-1 release by these fibroblasts, stimulated with lipopolysaccharide (LPS). HGFs were stimulated with LPS 10 μg/ml and treated with 15d-PGJ2 1 and 2 μg/ml, and ScLL 2 and 5 μg/ml, for 1 and 3h, and then evaluated for viability by MTT assay. Supernatant was collected to detect IL-6 and TGFβ-1 release, by ELISA. Positive control was cells kept in Dulbecco's Modified Eagle's Medium, and negative control was those kept in LPS. Data were analyzed by ANOVA and Dunnett's test (α = 0.05). No significant difference was found in viability among experimental groups at 1h (p > 0.05). Percentage of ScLL 5 µg/ml viable cells was similar to that of positive control at evaluated periods (p > 0.05), whereas the other groups had lower levels than the positive control (p < 0.05). IL-6 release was statistically higher for ScLL 5 μg/ml and 15d-PGJ2 2 µg/ml at 1h, compared with the other treated groups and positive control (p < 0.05). No significant differences were found among the groups at 3h (p > 0.05), except for ScLL 2 µg/ml and 15d-PGJ2 1 µg/ml, which showed lower IL-6 release compared with that of negative control (p < 0.05). No significant difference was found among the groups for TGFβ-1 release (p > 0.05). Results indicated that ScLL 5 μg/ml did not interfere in viability, and ScLL 2 µg/ml and 15d-PGJ2 1 µg/ml demonstrated reduced IL-6 release. Tested substances had no effect on TGFβ-1 release.


Subject(s)
Humans , Prostaglandin D2/analogs & derivatives , Lipopolysaccharides/pharmacology , Interleukin-6/metabolism , Plant Lectins/pharmacology , Transforming Growth Factor beta1/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Reference Values , Time Factors , Enzyme-Linked Immunosorbent Assay , Prostaglandin D2/pharmacology , Cell Survival/drug effects , Cells, Cultured , Analysis of Variance , Statistics, Nonparametric , Transforming Growth Factor beta1/drug effects , Gingiva/cytology
3.
Rev. chil. cardiol ; 37(2): 93-103, ago. 2018. tab, graf, ilus
Article in Spanish | LILACS | ID: biblio-959346

ABSTRACT

Resumen: Introducción: El ejercicio físico reduce la mortalidad cardiovascular y genera remodelado cardíaco. Altas cargas de entrenamiento pueden generar remodelado cardíaco adverso. Biomarcadores (BMC) de inflamación Interleukina 6 (IL-6) y de estrés oxidativo Malondialdehído (MDA), potencialmente pueden caracterizar la respuesta al esfuerzo. Objetivo: Evaluar actividad de IL-6 y MDA en respuesta a una maratón en atletas con distinto nivel de entrenamiento y remodelado cardíaco asociado. Sujetos y Métodos: Estudio prospectivo, simple ciego, incluyó 16 atletas que completaron la maratón de Santiago (42 k), separados según entrenamiento previo, grupo 1 (G1, n: 8): Alto ≥ 100 km/semana y grupo 2 (G2, n: 8): Bajo <100 km/semana). Se obtuvo pre y post maratón: niveles de IL-6, MDA y ecocardiografía Doppler transtorácica (ETT); cuantificando cámaras cardíacas izquierdas, derechas y deformación del ventrículo izquierdo (strain longitudinal). Se utilizaron las pruebas de Mann-Whitney, Wilcoxon y Kruskal-Wallis. Resultados: Edad G1: 38.13±7.18 años vs G2: 40.38±6.63 años (NS). Tiempo maratón G1: 185.75±14.87 min vs G2: 219.75±24.92 min (p<0.01). Masa del ventrículo izquierdo G1: 91±21 g/m2 vs G2: 73±12 g/m2 (p<0.01). Volumen aurícula izquierda G1: 39.4±12.6 ml/m2 vs 30.6±4.6 ml/m2 (p<0.01). FEVI G1: 55.8±3.3% vs G2: 58.6±6.7% (NS). MDA G1: PRE 0.17±0.13 uM/L, POST 0.67±0.59 uM/L, G2: PRE 0.29±0.24 uM/L, POST 1.01±1.15 uM/L (p<0.01). IL-6 G1: PRE 2.50±1.35 pg/ml, POST 93.91±27.23 pg/ml vs G2: PRE 4.65±5.89 pg/ml, POST 97.83±30.72 pg/ml (NS). Conclusión: El ejercicio físico aumenta los BMC de inflamación y estés oxidativo (IL-6, MDA). Un entrenamiento físico de alta intensidad disminuye la respuesta de estrés oxidativo y se asocia a un mayor remodelado cardíaco.


Abstract: Background: Exercise reduces cardiovascular mortality and generates cardiac remodeling. High training loads can induce adverse cardiac remodeling, and its associated cardiac remodeling. Therefore, interleukin 6 (IL 6) and malondialdehyde (MDA), biomarkers of inflammatory response and oxidative stress respectively, may have a role in stratifying this risk. Objective: To assess the activity of IL-6 and MDA in response to a marathon race in athletes with different previous training status. Subjects And Methods: Prospective, single-blind study involving 16 male athletes that finished the Santiago Marathon (42 k), allocated into two groups according to their previous training: Group 1 (G1, n: 8) with high training (≥ 100 km/weekly) and Group 2 (G2, n: 8) with low training (< 100 km/weekly). Before and after the race serum levels of IL-6, MDA and transthoracic Doppler echocardiography for cardiac chamber quantification and left ventricle deformation (longitudinal strain) were measured. Mann-Whitney, Wilcoxon, and Kruskal-Wallis tests were used to assess statistical significance. Results: Age G1: 38.13±7.18 years-old vs G2: 40.38±6.63 years-old (NS). Marathon finishing time G1: 185.75±14.87 min vs G2: 219.75±24.92 min (p<0.01). Left ventricle mass G1: 91±21 g/m2 vs G2: 73±12 g/m2 (p<0.01). Left atrium volume G1: 39.4±12.6 ml/m2 vs 30.6±4.6 ml/m2 (p<0.01). LVEF G1: 55.8±3.3% vs G2: 58.6±6.7% (NS). MDA G1: PRE 0.17±0.13 uM/L, POST 0.67±0.59 uM/L, G2: PRE 0.29±0.24 uM/L, POST 1.01±1.15 uM/L (p<0.01). IL-6 G1: PRE 2.50±1.35 pg/ml, POST 93.91±27.23 vs G2: PRE 4.65±5.89 pg/ml, POST 97.83±30.72 pg/ml (NS). Conclusion: Physical exercise generates a rise in biomarkers (IL-6, MDA). Athletes with high-intensity training level have a diminished oxidative stress response post effort and greater cardiac remodeling.


Subject(s)
Humans , Male , Adolescent , Adult , Middle Aged , Young Adult , Interleukin-6/metabolism , Ventricular Remodeling/physiology , Exercise Therapy/methods , Malondialdehyde/metabolism , Echocardiography , Biomarkers , Single-Blind Method , Prospective Studies , Oxidative Stress/physiology , Athletes , Heart Ventricles/diagnostic imaging
4.
Acta cir. bras ; 33(6): 483-490, June 2018. tab, graf
Article in English | LILACS | ID: biblio-949354

ABSTRACT

Abstract Purpose: To evaluate the effects of hypothermia treatment on meconium-induced inflammation. Methods: Fifteen rats were instilled with human meconium (MEC, 1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. Eight rats that were ventilated and not instilled with meconium served as a sham group. In MEC-hypothermia group, the body temperature was lowered to 33±0.5°C. Analysis of the blood gases, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage (BAL) fluid samples, and histological analyses of the lungs were performed. Results: The BAL fluid TNF-α, IL-1β, IL-6 and IL-8 concentrations were significantly higher in the MEC-hypothermia group than in the MEC-normothermia (p < 0.001, p < 0.001, p = 0.001, p < 0.001, respectively) and sham-controlled groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). Conclusion: Meconium-induced inflammatory cytokine production is affected by the body temperature control.


Subject(s)
Animals , Male , Pneumonia/pathology , Meconium Aspiration Syndrome/pathology , Meconium Aspiration Syndrome/therapy , Hypothermia, Induced/methods , Pneumonia/metabolism , Pneumonia/therapy , Enzyme-Linked Immunosorbent Assay , Bronchoalveolar Lavage Fluid/chemistry , Meconium Aspiration Syndrome/metabolism , Reproducibility of Results , Interleukin-8/metabolism , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Treatment Outcome , Rats, Wistar , Disease Models, Animal , Interleukin-1beta/metabolism , Luminescent Measurements/methods , Lung/pathology
5.
Braz. dent. j ; 29(3): 301-308, May-June 2018. tab
Article in English | LILACS | ID: biblio-951549

ABSTRACT

Abstract There are few studies on the clinical and immunological periodontal status of intensive care unit (ICU) in-patients. The aim of the present study was to evaluate the periodontal condition among ICU in-patients through clinical and immunological periodontal parameters. From the sample of 373 hospitalized ICU patients, 182 were submitted' to a thorough clinical periodontal and immunological evaluation. Data on bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) were collected and gingival sulcular fluid samples were quantified through ELISA on IL-1, IL-6, and MMP-2 for immunological evaluation. Data was statistically analyzed by Chi-square, Fisher's exact, Mann-Whitney tests, and Sperman's correlation and multivariate logistic regression analysis. A high dental plaque index and a high prevalence of periodontitis (48.3%), mostly in moderate and localized chronic form, were observed. Individuals with periodontitis presented higher levels of IL-1 and MMP-2, while individuals with cardiovascular disease (CVD) and individuals with two or more systemic diseases (MSD) presented higher levels of IL-1; diabetes mellitus (DM) and MSD individuals presented higher levels of IL-6. A positive association was found between the severity of periodontitis and CVD (OR 2.2; CI = 1.11-4.42). This study reported a 48.3% of the prevalence of periodontitis in ICU patients and a positive association between the severity of periodontitis and CVD. Additionally, higher levels of IL-1 and MMP-2 were found in individuals with periodontitis, higher levels of IL-6 were found in individuals with DM, and higher levels of IL-1 were found in individuals with CVD.


Resumo Existem poucos estudos sobre o estado clínico periodontal e imunológico de pacientes em unidade de terapia intensiva (UTI). O objetivo do presente estudo foi avaliar a condição periodontal entre os pacientes internados na UTI através de parâmetros clínicos periodontais e imunológicos. De uma amostra inicial de 373 pacientes internados em UTI, 183 foram submetidos a exame periodontal completo e análise imunológica. Os dados sobre o sangramento na sondagem (BOP), profundidade de sondagem (PD) e nível clínico de inserção (CAL) foram coletados e as amostras de fluido sulcular gengival foram quantificadas para avaliação imunológica através de ELISA para IL-1, IL-6 e MMP-2. Os dados foram analisados estatisticamente pelos testes de Qui-quadrado, exato de Fischer, Mann-Whitney, correlação de Sperman e análise de regressão logística multivariada. Foi observado um alto índice de placa dental e uma alta prevalência de periodontite (48,3%), principalmente na forma crônica moderada e localizada. Os indivíduos com periodontite apresentaram níveis mais altos de IL-1 e MMP-2, enquanto indivíduos com doença cardiovascular (CVD) e com mais de duas doenças sistêmicas (MSD) apresentaram níveis mais altos de IL-1 e os com diabetes mellitus (DM) e MSD apresentaram níveis mais elevados de IL-6. Foi encontrada associação positiva entre a gravidade da periodontite e CVD (OR 2.2; IC = 1,11-4,42). Este estudo reportou uma prevalência de periodontite em 48.3% dos pacientes em UTI e uma associação positiva entre ocorrência de periodontite e CVD. Além disso, níveis mais elevados de IL-1 e MMP-2 foram encontrados em indivíduos com periodontite, de IL-6 em indivíduos com DM e de IL-1 em indivíduos com CVD.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Periodontal Diseases/complications , Periodontal Diseases/immunology , Inpatients , Intensive Care Units , Periodontal Diseases/pathology , Periodontal Pocket/immunology , Respiratory Tract Diseases/complications , Cardiovascular Diseases/complications , Periodontal Index , Dental Plaque Index , Cross-Sectional Studies , Gingival Crevicular Fluid/metabolism , Interleukin-6/metabolism , Interleukin-1/metabolism , Periodontal Attachment Loss/immunology , Matrix Metalloproteinase 2/metabolism , Diabetes Complications
6.
Braz. j. med. biol. res ; 51(8): e6921, 2018. graf
Article in English | LILACS | ID: biblio-951749

ABSTRACT

Preeclampsia is one of the most frequent and difficult illnesses in pregnancy, which jeopardizes both mother and fetus. There are several diagnostic criteria for preeclampsia. However, the preeclampsia-associated myocardial damage has not been described. In this study, we employed reduced uterine perfusion pressure (RUPP) to generate a rat model of preeclampsia for the evaluation of myocardial damage in late-gestation rats. The expressions of cardiac injury markers were analyzed by immunohistochemistry and ELISA. The arterial pressure and myocardial tissue velocities were also measured. The role of interleukin (IL)-6 in RUPP-associated myocardial damage was further explored. The results showed that RUPP rats had significant myocardial damage, as demonstrated by the high expressions of myoglobin, creatine kinase isoenzyme, cardiac troponin I, and brain natriuretic peptide. In addition, RUPP increased the mean arterial pressure and the early transmitral flow velocity to mitral annulus early diastolic velocity ratio (E/Ea). Furthermore, IL-6 deteriorated these abnormalities, whereas inhibition of IL-6 significantly relieved them. In conclusion, our study demonstrated that RUPP rats displayed myocardial damage in an IL-6-dependent manner.


Subject(s)
Animals , Female , Pregnancy , Pre-Eclampsia/metabolism , Interleukin-6/metabolism , Cardiomyopathies/etiology , Myocardium/metabolism , Perfusion , Pre-Eclampsia/etiology , Random Allocation , Interleukin-6/antagonists & inhibitors , Rats, Sprague-Dawley , Echocardiography, Doppler, Color , Troponin I/metabolism , Natriuretic Peptide, Brain/metabolism , Disease Models, Animal , Creatine Kinase, MB Form/metabolism , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/metabolism , Arterial Pressure , Heart/drug effects , Heart/diagnostic imaging , Cardiomyopathies/metabolism , Cardiomyopathies/pathology , Myoglobin/metabolism
7.
Braz. j. med. biol. res ; 51(8): e6896, 2018. graf
Article in English | LILACS | ID: biblio-951743

ABSTRACT

Excessive exposure to ultraviolet (UV) rays can cause damage of the skin and may induce cancer, immunosuppression, photoaging, and inflammation. The long non-coding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) is involved in multiple human biological processes. However, its role in UVB-induced keratinocyte injury is unclear. This study was performed to investigate the effects of HOTAIR in UVB-induced apoptosis and inflammatory injury in human keratinocytes (HaCaT cells). Quantitative real-time polymerase chain reaction was performed to analyze the expression levels of HOTAIR, PKR, TNF-α, and IL-6. Cell viability was measured using trypan blue exclusion method and cell apoptosis using flow cytometry and western blot. ELISA was used to measure the concentrations of TNF-α and IL-6. Western blot was used to measure the expression of PKR, apoptosis-related proteins, and PI3K/AKT and NF-κB pathway proteins. UVB induced HaCaT cell injury by inhibiting cell viability and promoting cell apoptosis and expressions of IL-6 and TNF-α. UVB also promoted the expression of HOTAIR. HOTAIR suppression increased cell viability and decreased apoptosis and expression of inflammatory factors in UVB-treated cells. HOTAIR also promoted the expression of PKR. Overexpression of HOTAIR decreased cell viability and increased cell apoptosis and expression of inflammatory factors in UVB-treated cells by upregulating PKR. Overexpression of PKR decreased cell viability and promoted cell apoptosis in UVB-treated cells. Overexpression of PKR activated PI3K/AKT and NF-κB pathways. Our findings identified an essential role of HOTAIR in promoting UVB-induced apoptosis and inflammatory injury by up-regulating PKR in keratinocytes.


Subject(s)
Humans , Keratinocytes/metabolism , Apoptosis/physiology , eIF-2 Kinase/metabolism , Apoptosis Inducing Factor/metabolism , RNA, Long Noncoding/metabolism , Ultraviolet Rays/adverse effects , Gene Expression , Keratinocytes/radiation effects , Up-Regulation , Cell Survival/physiology , NF-kappa B/drug effects , NF-kappa B/metabolism , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Apoptosis/radiation effects , Phosphatidylinositol 3-Kinases/metabolism , Inflammation/etiology
8.
Int. j. morphol ; 35(2): 723-732, June 2017. ilus
Article in English | LILACS | ID: biblio-893046

ABSTRACT

Tumor necrosis factor alpha (TNF-a) and interleukin (IL)-6, are prominent mediators of inflammation and have been confirmed to be elevated in at least a subgroup of women with polycystic ovary syndrome (PCOS). In this study, the effects of Silymarin (SLM) on the expression TNF-a, IL-6, CRP and symptoms of PCOS were studied. In this research, PCOS was induced by injection of Estradiol Valerate. PCOS rats were divided into control and experimental groups received intraperitoneal injection SLM extract daily. After syndrome induction, ovaries were collected for histological and immunohistochemical evaluations. Serum IL-6 was detected by the ELISA kit. The results indicated the significant reduction in inflammatory markers and significant changes follicular layers thickness in the treatment group as compared with control. It can be concluded that having anti-inflammatory substances, Silymarin is effective in symptoms of this syndrome and metabolic syndrome.


El factor de necrosis tumoral alfa (TNF-a) y la interleucina (IL) -6 son mediadores prominentes de la inflamación y se ha confirmado que están elevados en al menos un subgrupo de mujeres con síndrome de ovario poliquístico (SOP). En este estudio se estudiaron los efectos de Silymarin (SLM) en la expresión TNF-a, IL-6, PCR y síntomas de SOP. El SOP fue inducido por inyección de valerato de estradiol. Las ratas SOP se dividieron en grupos control y los grupos experimentales recibieron diariamente un extracto de SLM por inyección intraperitoneal. Después de la inducción del síndrome, los ovarios se analizaron mediante histología e inmunohistoquímica. Se detectó IL-6 en suero mediante el kit ELISA. Los resultados indicaron una reducción significativa en los marcadores inflamatorios y cambios significativos en el espesor de las capas foliculares en el grupo de tratamiento en comparación con el control. Se puede concluir que con sustancias anti-inflamatorias, Silymarin es eficaz en los síntomas de este síndrome y el síndrome metabólico.


Subject(s)
Animals , Female , Rats , Anti-Inflammatory Agents/pharmacology , Polycystic Ovary Syndrome/metabolism , Silymarin/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Immunohistochemistry , Inflammation , Interleukin-6/metabolism , Rats, Wistar , Tumor Necrosis Factor-alpha/drug effects
9.
Acta cir. bras ; 32(5): 396-406, May 2017. tab, graf
Article in English | LILACS | ID: biblio-837708

ABSTRACT

Abstract Purpose: To determine the effects of propofol and ketamine anesthesia on liver regeneration in rats after partial hepatectomy (PHT). Methods: Male Wistar albino rats were assigned randomly to four groups of 10. Anesthesia was induced and maintained with propofol in groups 1 and 2, and with ketamine in groups 3 and 4. PHT was undertaken in groups 1 and 3. Rats in groups 2 and 4 (control groups) underwent an identical surgical procedure, but without PHT. At postoperative day-5, rats were killed. Regenerated liver was removed, weighed, and evaluated (by immunohistochemical means) for expression of inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), apoptosis protease-activating factor (APAF)-1, and proliferating cell nuclear antigen (PCNA). Also, blood samples were collected for measurement of levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Results: Between groups 2 and 4, there were no differences in tissue levels of iNOS, eNOS, and APAF-1 or plasma levels of TNF-α and IL-6. eNOS expression was similar in group 1 and group 3. Expression of iNOS and APAF-1 was mild-to-moderate in group 1, but significantly higher in group 3. Groups 1 and 3 showed an increase in PCNA expression, but expression in both groups was comparable. Plasma levels of TNF-α and IL-6 increased to a lesser degree in group 1 than in group 3. Conclusion: Propofol, as an anesthetic agent, may attenuate cytokine-mediated upregulation of iNOS expression and apoptosis in an animal model of liver regeneration after partial hepatectomy.


Subject(s)
Animals , Male , Propofol/pharmacology , Apoptosis , Anesthetics, Intravenous/pharmacology , Nitric Oxide Synthase Type II/metabolism , Ketamine/pharmacology , Liver Regeneration/drug effects , Random Allocation , Propofol/metabolism , Up-Regulation , Interleukin-6/metabolism , Interleukin-6/blood , Rats, Wistar , Proliferating Cell Nuclear Antigen/metabolism , Anesthetics, Intravenous/metabolism , Models, Animal , Nitric Oxide Synthase Type III/metabolism , Apoptotic Protease-Activating Factor 1/metabolism , Hepatectomy , Ketamine/metabolism
10.
Yonsei Medical Journal ; : 206-216, 2017.
Article in English | WPRIM | ID: wpr-126255

ABSTRACT

PURPOSE: Angiopoietin-1 (Ang1) is a critical factor for vascular stabilization and endothelial survival via inhibition of endothelial permeability and leukocyte- endothelium interactions. Hence, we hypothesized that treatment with umbilical cord mesenchymal stem cells (UCMSCs) carrying the Ang1 gene (UCMSCs-Ang1) might be a potential approach for acute lung injury (ALI) induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: UCMSCs with or without transfection with the human Ang1 gene were delivered intravenously into rats one hour after intra-abdominal instillation of LPS to induce ALI. After the rats were sacrificed at 6 hours, 24 hours, 48 hours, 8 days, and 15 days post-injection of LPS, the serum, the lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested for analysis, respectively. RESULTS: Administration of fluorescence microscope confirmed the increased presence of UCMSCs in the injured lungs. The evaluation of UCMSCs and UCMSCs-Ang1 actions revealed that Ang1 overexpression further decreased the levels of the pro-inflammatory cytokines TNF-α, TGF-β1, and IL-6 and increased the expression of the anti-inflammatory cytokine IL-10 in the injured lungs. This synergy caused a substantial decrease in lung airspace inflammation and vascular leakage, characterized by significant reductions in wet/dry ratio, differential neutrophil counts, myeloperoxidase activity, and BALF. The rats treated by UCMSCs-Ang1 showed improved survival and lower ALI scores. CONCLUSION: UCMSCs-Ang1 could improve both systemic inflammation and alveolar permeability in ALI. UC-derived MSCs-based Ang1 gene therapy may be developed as a potential novel strategy for the treatment of ALI.


Subject(s)
Acute Lung Injury/chemically induced , Angiopoietin-1/genetics , Animals , Bronchoalveolar Lavage Fluid , Cytokines/metabolism , Endotoxins , Genetic Therapy , Interleukin-10/metabolism , Interleukin-6/metabolism , Leukocyte Count , Lipopolysaccharides , Lung/metabolism , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Neutrophils/metabolism , Rats , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Umbilical Cord/cytology
11.
Braz. j. med. biol. res ; 50(1): e5594, 2017. graf
Article in English | LILACS | ID: biblio-839239

ABSTRACT

We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH) and the protective effects mediated by angiotensin 1-7 [Ang(1-7)]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g) to normoxia control, CIH, Ang(1-7)-treated normoxia, and Ang(1-7)-treated CIH groups. Systolic blood pressure (SBP) was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA) was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7) induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7) treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7) treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7) might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.


Subject(s)
Animals , Male , Rats , Acute Kidney Injury/drug therapy , Angiotensin I/administration & dosage , Oxidative Stress/drug effects , Peptide Fragments/administration & dosage , Disease Models, Animal , Inflammation/drug therapy , Interleukin-6/metabolism , Kidney/metabolism , Kidney/pathology , Rats, Sprague-Dawley
12.
Biol. Res ; 50: 26, 2017. graf
Article in English | LILACS | ID: biblio-950876

ABSTRACT

BACKGROUND: CCL2 was up-regulated in neurons and involved in microglia activation and neurological decline in mice suffering from hepatic encephalopathy (HE). However, no data exist concerning the effect of neuron-derived CCL2 on microglia activation in vitro. METHODS: The rats were pretreated with CCL2 receptor inhibitors (INCB or C021, 1 mg/kg/day i.p.) for 3 days prior to thioacetamide (TAA) administration (300 mg/kg/day i.p.) for inducing HE model. At 8 h following the last injection (and every 4 h after), the grade of encephalopathy was assessed. Blood and whole brains were collected at coma for measuring CCL2 and Iba1 expression. In vitro, primary neurons were stimulated with TNF-α, and then the medium were collected for addition to microglia cultures with or without INCB or C021 pretreatment. The effect of the medium on microglia proliferation and activation was evaluated after 24 h. RESULTS: CCL2 expression and microglia activation were elevated in the cerebral cortex of rats received TAA alone. CCL2 receptors inhibition improved neurological score and reduced cortical microglia activation. In vitro, TNF-α treatment induced CCL2 release by neurons. Medium from TNF-α stimulated neurons caused microglia proliferation and M1 markers expression, including iNOS, COX2, IL-6 and IL-1ß, which could be suppressed by INCB or C021 pretreatment. The medium could also facilitate p65 nuclear translocation and IκBα phosphorylation, and NF-κB inhibition reduced the increased IL-6 and IL-1ß expression induced by the medium. CONCLUSION: Neuron-derived CCL2 contributed to microglia activation and neurological decline in HE. Blocking CCL2 or inhibiting microglia excessive activation may be potential strategies for HE.


Subject(s)
Animals , Rats , Hepatic Encephalopathy/metabolism , Microglia/metabolism , Chemokine CCL2/metabolism , Receptors, Chemokine/antagonists & inhibitors , Neurons/metabolism , Thioacetamide , Gene Expression , Hepatic Encephalopathy/chemically induced , Hepatic Encephalopathy/therapy , Interleukin-6/metabolism , Microglia/drug effects , Chemokine CCL2/antagonists & inhibitors , Culture Media/pharmacology , Disease Models, Animal , Nervous System Diseases
13.
Biol. Res ; 50: 42, 2017. tab, graf
Article in English | LILACS | ID: biblio-950888

ABSTRACT

BACKGROUND: Fresh frozen plasma (FFP) administration may increase the risk of nosocomial infections in parallel with the development of immune modulation. This could be driven by soluble mediators, possibly influencing the in vitro activation of human U937 monocyte cells, in a manner dependent on the age of the donors. METHODS: FFP donors were stratified into groups of 19-30 years, 31-40 years or 41-50 years, and U937 cells were cultured with FFP (alone or plus lipopolysaccharide-LPS) for 24 h. Both in FFP and supernatants, TNF, IL-1ß, IL-6, and IL-10 levels were measured by ELISA. Additionally, CD11B, TLR2, and CASP3 gene expression were measured by qtPCR in U937 cells. Total phagocytic activity was also assayed. RESULTS: Elevated IL-10, but low TNF and IL-1ß levels were measured in FFP from individuals aged 19-40 years, whereas in individuals aged 41-50 years FFP were characterized by equalized TNF and IL-10 levels. Elevated IL-6 levels were found in all FFP samples, especially in those from the oldest individuals. FFP stimulation was associated with striking modifications in cytokine production in an age-dependent way. Exposure to FFP attenuates the response to LPS. TLR2 and CD11B expression were enhanced regardless of the age of plasma donors, although CASP3 expression was increased only when FFP from individuals aged 19-40 years were tested. Phagocytosis decreased after exposure to FFP regardless of donor age. CONCLUSION: Our results suggest that soluble mediators in FFP may modulate the functioning of monocytes. Interestingly, this effect appears to be partially influenced by the age of donors.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Plasma/immunology , Blood Donors , Monocytes/immunology , Cytokines/immunology , U937 Cells/immunology , Enzyme-Linked Immunosorbent Assay , Monocytes/physiology , Age Factors , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-10/metabolism , Interleukin-1beta/metabolism
14.
Arq. bras. oftalmol ; 79(6): 357-362, Nov.-Dec. 2016. graf
Article in English | LILACS | ID: biblio-838758

ABSTRACT

ABSTRACT Purpose: We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. Methods: Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS). Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. Results: Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. Conclusions: Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.


RESUMO Objetivo: Avaliamos o efeito do licopeno, um carotenóide dietético e um potente anti-oxidante, sobre a inflamação ocular e estresse oxidativo em modelo de uveíte experimental. Métodos: Uveíte foi induzida por endotoxina (EIU) em ratos Sprague-Dawley por uma única injeção subcutânea de 200 ug de lipopolissacárido (LPS). A indução de EIU foi precedida por injeção intraperitoneal de licopeno em uma dose de 10 mg/kg (grupo LPS + Licopeno) ou veículo de mesmo volume (grupo LPS + Veículo), durante 3 dias consecutivos. O grupo controle positivo recebeu uma dose de 1 mg/kg de Dexametasona (grupo DEX + LPS) e o grupo controle negativo recebeu doses diárias de veículo mas sem LPS (grupo Controle Veículo). Vinte e quatro horas após a administração do LPS, os olhos foram enucleados, humor aquoso foi recolhido, e o número de células infiltrativas, a concentração de proteína, assim como os níveis de óxido nítrico (NO), fator de necrose tumoral α (TNF-α), interleucina-6 e marcadores de estresse oxidativo foram determinados no humor aquoso. Além disso, a resposta inflamatória foi avaliada clinicamente e histologicamente. Resultados: As células infiltrativas, concentração de proteína, o NO, TNF-α, interleucina-6 foram significativamente elevados no humor aquoso de ratos do grupo Grupo LPS + Veículo quando comparados ao Grupo Controle Veículo. O tratamento com licopeno diminuiu significativamente estes aumentos. Comparado ao Grupo LPS + Veículo, o licopeno reduziu significativamente as concentrações no humor aquoso dos marcadores de estresse oxidativo e NO (de 0,29 ± 0,1 μM para 0,19 ± 0,1 μM, p=0,003), o TNF-α (de 71,0 ± 22,3 ng/ml para 50,1 ± 2,1 ng/ml, p=0,043), interleucina-6 (de 121,6 ± 3,0 pg/ml para 111,1 ± 5,6 pg/ml, p=0,008). Do mesmo modo, o aumento do número de células infiltrativas no tecido uveal em seções histológicas foi significativamente inibido pelo licopeno, a pontuação inflamatória diminuiu de 2,0 ± 0,0 para 0,4 ± 0,5, p=0,001. Embora, não tenha sido estatisticamente significativo, o licopeno reduziu a contagem de células infiltrativas e a concentração de proteínas no humor aquoso. Conclusões: Estes resultados sugerem que o licopeno pode ter efeitos benéficos no tratamento da inflamação ocular, através dos seus efeitos anti-inflamatórios e antioxidantes.


Subject(s)
Animals , Rats , Uveitis/drug therapy , Carotenoids/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Aqueous Humor/metabolism , Uveitis/chemically induced , Uveitis/pathology , Lipopolysaccharides , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Rats, Sprague-Dawley , Oxidative Stress , Disease Models, Animal , Eye/pathology , Lycopene , Nitric Oxide/metabolism
15.
Arq. bras. cardiol ; 107(2): 131-136, Aug. 2016. tab, graf
Article in English | LILACS | ID: lil-794563

ABSTRACT

Abstract Background: Interleukin-6 (IL-6) is implicated in the pathogenesis of coronary heart disease (CHD), and IL-6 expression has associated with reduced DNA methylation of its gene promoter. However, there are no data on IL-6 promoter methylation and the risk of CHD. Objective: To examine whether IL-6 promoter methylation measured in blood leukocyte DNA is associated with CHD risk. Methods: A total of 212 cases with CHD and 218 controls were enrolled. Methylation at two CpG sites in IL-6 promoter was measured by bisulfite pyrosequencing, and the mean IL-6 methylation was calculated by averaging the methylation measures of the two CpGs. Results: Mean methylation level in IL-6 promoter in CHD cases was significantly lower than that in controls (p = 0.023). Logistic regression analysis showed that IL-6 methylation was inversely associated with the risk of CHD. The odds ratios (ORs) of CHD for subjects in the second and first (lowest) tertile of IL-6 methylation were 1.87 (95% CI = 1.10‑3.20) and 2.01 (95% CI = 1.19-3.38) (ptrend = 0.013), respectively, compared to subjects in the third (highest) tertile. The IL-6 hypomethylation-related risk estimates tended to be stronger for acute myocardial infarction (ptrend = 0.006). CpG position-specific analysis showed that hypomethylation of position 1 conferred a more pronounced increase in CHD risk than that of position 2. Conclusion: These findings suggest that DNA hypomethylation of IL-6 promoter is associated with the increased risk for CHD, especially for acute myocardial infarction. The two distinct CpGs in IL-6 may contribute differently to the development of CHD.


Resumo Fundamento: Interleucina-6 (IL-6) está implicada na patogênese de doença arterial coronariana (DAC), sendo sua expressão associada com redução da metilação de DNA do promotor do seu gene. Entretanto, não há dados sobre metilação do promotor de IL-6 e risco de DAC. Objetivo: Verificar se a metilação do promotor de IL-6 medida no DNA de leucócitos sanguíneos acha-se associada com risco de DAC. Métodos: este estudo arrolou 212 casos com DAC e 218 controles. Metilação em dois sítios de CpG no promotor de IL-6 foi medida por pirosequenciamento de bissulfito, sendo a metilação média de IL-6 calculada pela média das medidas de metilação dos dois CpGs. Resultados: A média do nível de metilação no promotor de IL-6 nos casos de DAC foi significativamente mais baixa do que nos controles (p = 0,023). Análise de regressão logística mostrou associação inversa entre metilação de IL-6 e risco de DAC. As razões de chance (OR) de DAC para indivíduos no segundo e no primeiro (mais baixo) tercis de metilação de IL-6 foram 1,87 (IC 95%: 1,10-3,20) e 2,01 (IC 95%: 1,19-3,38) (ptrend = 0,013), respectivamente, comparadas à de indivíduos no terceiro (mais alto) tercil. As estimativas de risco relacionado à hipometilação de IL-6 tenderam a ser mais fortes para infarto agudo do miocárdio (ptrend = 0,006). Análise com especificidade de posição de CpG mostrou que hipometilação na posição 1 conferiu maior elevação no risco de DAC do que na posição 2. Conclusão: Tais achados sugerem que a hipometilação de DNA do promotor de IL-6 está associada com elevado risco de DAC, especialmente para infarto agudo do miocárdio. Os dois CpGs distintos no promotor de IL-6 podem contribuir de modo diferente para o desenvolvimento de DAC.


Subject(s)
Humans , Male , Female , Aged , Interleukin-6/genetics , Promoter Regions, Genetic , CpG Islands , DNA Methylation , Coronary Disease/genetics , Genetic Predisposition to Disease/genetics , Interleukin-6/metabolism , Sequence Analysis, DNA , Angina, Unstable/genetics , Myocardial Infarction/genetics
16.
Rev. bras. reumatol ; 56(4): 299-308, July-Aug. 2016. tab, graf
Article in English | LILACS | ID: lil-792759

ABSTRACT

ABSTRACT Objective: To evaluate 18F-fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography–computed tomography (PET–CT) and serum levels of different cytokines and matrix metalloproteinases (MMPs) in patients with Takayasu arteritis (TA) and associations with disease activity. Methods: Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax) of 18F-FDG in arterial walls was determined by PET–CT scans. TA patients were classified as active disease, inactive disease and possible active disease. Results: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p < 0.001). Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p < 0.0001). Patients with active disease had higher serum TNFα levels than patients with inactive disease (p = 0.049) while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p = 0.046). Patients with active disease had higher SUVmax values than those with inactive disease (p = 0.042). By receiver operating characteristic (ROC) curve SUVmax was predictive of active disease in TA and values ≥1.3 were associated with disease activity (p = 0.039). Serum TNF-α levels were higher in patients with SUVmax ≥ 1.3 than <1.3 (p = 0.045) and controls (p = 0.012). Serum IL-6 levels were higher in patients with SUVmax ≥ 1.3 than in controls (p < 0.001). No differences regarding other biomarkers were found between TA patients and controls. Conclusions: Higher serum IL-6 and TNFα levels as well as higher 18F-FDG uptake in arterial wall are associated with active TA.


RESUMO Objetivo: Avaliar a captação de 18F-fluordesoxiglicose (FDG) na tomografia por emissão de pósitrons – tomografia computadorizada (PET-CT) – e os níveis séricos de diferentes citocinas e da metaloproteinases da matriz (MMP) em pacientes com arterite de Takayasu (AT) e associações com a atividade da doença. Métodos: Foram mensurados os níveis séricos do fator de necrose tumoral-α (TNF-α), interleucina (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 e MMP-9 em 36 pacientes com AT e 36 controles. O valor padronizado de captação máximo (SUVmax) de 18F-FDG nas paredes arteriais foi determinado por exames de PET-CT. Os pacientes com AT foram classificados como doença ativa, doença inativa e possível doença ativa. Resultados: Os níveis séricos de IL-6 e MMP-3 foram mais altos em pacientes com AT do que nos controles (p < 0,001). Os níveis séricos de IL-6 foram mais elevados em pacientes com doença ativa e em pacientes com possível doença ativa do que naqueles com doença inativa (p < 0,0001). Os pacientes com doença ativa apresentaram níveis séricos mais elevados de TNF-α do que os pacientes com doença inativa (p = 0,049), enquanto os indivíduos com possível doença ativa apresentaram maiores níveis séricos de IL-18 do que os pacientes com doença inativa (p = 0,046). Aqueles com doença ativa apresentaram maiores valores de SUVmax do que aqueles com doença inativa (p = 0,042). De acordo com a curva ROC, o SUVmax foi capaz de predizer a doença ativa na AT e valores ≥ 1,3 estavam associados à atividade da doença (p = 0,039). Os níveis séricos de TNF-α foram maiores em pacientes com SUVmax ≥ 1,3 do que naqueles com valor < 1,3 (p = 0,045) e controles (p = 0,012). Os níveis séricos de IL-6 foram mais elevados em pacientes com SUVmax ≥ 1,3 do que nos controles (p < 0,001). Não foram encontradas diferenças em relação a outros biomarcadores entre pacientes com AT e controles. Conclusões: Níveis séricos elevados de IL-6 e TNF-α, bem como uma maior captação arterial de 18F-FDG, estão associados à AT ativa.


Subject(s)
Humans , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Takayasu Arteritis/metabolism , Takayasu Arteritis/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Case-Control Studies , Cytokines/metabolism , Radiopharmaceuticals/administration & dosage , Fluorodeoxyglucose F18/administration & dosage , Matrix Metalloproteinases/metabolism
17.
Acta cir. bras ; 31(7): 472-478, tab, graf
Article in English | LILACS | ID: lil-787262

ABSTRACT

ABSTRACT PURPOSE: To investigate the effects of preoperative rectal ozone insufflation on surgical wound healing over the proinflammatory cytokines and histopathological changes. METHODS: Twenty one rabbits were divided into 3 groups. Sham, surgical wound, and ozone applied (6 sessions, every other day 70 µg/mL in 12 mL O2-O3 mixture rectally) surgical wound groups were created. TNF-alpha and IL-6 levels from all rabbits were studied at the basal, 24th hour, and 72nd hour. The histopathological examination was done by removing the surgical scar tissue at the end of 72nd hour. RESULTS: TNF-alfa and IL-6 levels were significantly lower compared to the control group, in the rabbits treated with ozone. The increase in angiogenesis, the decrease in the number of inflammatory cells, epidermal and dermal regeneration, better collagen deposition, and increased keratinisation in stratum corneum were observed in the histopathological examination. It was determined that the wound healing noticeably accelerated in the ozone group. CONCLUSION: Preoperative rectal ozone insufflation had a positive effect on surgical wound healing in acute period.


Subject(s)
Animals , Rabbits , Ozone/pharmacology , Wound Healing/drug effects , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , Surgical Wound/drug therapy , Ozone/administration & dosage , Preoperative Care/methods , Insufflation/methods , Treatment Outcome , Surgical Wound/pathology , Granulation Tissue/pathology , Anti-Inflammatory Agents/therapeutic use
18.
Acta cir. bras ; 31(6): 382-388, graf
Article in English | LILACS | ID: lil-785018

ABSTRACT

ABSTRACT PURPOSE: To investigate the regulatory roles of neutrophil elastase (NE) and matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: To construct LPS-induced ALI mouse models, wild-type C57BL/6 mice were administered 5.0 mg/kg of LPS through endotracheal, and/or 1.0 mg/kg of ONO-5046, and/or 20.0 mg/kg of chemically modified tetracycline-3 (CMT-3) by gavage. The levels of MMP-9, tissue inhibitor of metalloprotease-1, interleukin (IL)-6 were detected by real time RT-PCR at 6 h, 24 h and 48 h, and tumor necrosis factor (TNF), lung wet-dry weight ratio, white blood cell (WBC) count and polymorphonuclear (PMN) count in bronchoalveolar lavage fluid (BALF) were tested at 48 h after administration. The 5-day survival analysis of the ALI mice was also performed. RESULTS: Both ONO-5046 and CMT-3, regardless of being used individually or combined, significantly reduced the levels of MMP-9, IL-6, and TNF in lung tissue as well as in BALF, and the WBC and PMN count in BALF. Combined treatment with ONO-5046 and CMT-3 remarkably improved the survival rate of ALI mice. CONCLUSION: Neutrophil elastase synergizes with matrix metalloproteinase-9 to promote and regulate the release of inflammatory mediators and the infiltration of inflammatory cells, consequently affecting the survival of lipopolysaccharide-induced acute lung injury mice.


Subject(s)
Animals , Sulfonamides/administration & dosage , Tetracyclines/administration & dosage , Leukocyte Elastase/metabolism , Matrix Metalloproteinase 9/metabolism , Acute Lung Injury/enzymology , Glycine/analogs & derivatives , Time Factors , Bronchoalveolar Lavage Fluid/cytology , Survival Analysis , Lipopolysaccharides , Interleukin-6/metabolism , Inflammation Mediators/metabolism , Leukocyte Elastase/drug effects , Tissue Inhibitor of Metalloproteinase-1/metabolism , Matrix Metalloproteinase 9/analysis , Matrix Metalloproteinase 9/drug effects , Tumor Necrosis Factors/metabolism , Disease Models, Animal , Acute Lung Injury/chemically induced , Acute Lung Injury/blood , Glycine/administration & dosage , Leukocyte Count , Mice, Inbred C57BL , Neutrophils
19.
Clinics ; 71(6): 344-350, tab, graf
Article in English | LILACS | ID: lil-787423

ABSTRACT

OBJECTIVE: The aim of the present study was to assess nasal mucociliary clearance, mucus properties and inflammation in smokers and subjects enrolled in a Smoking Cessation Program (referred to as quitters). METHOD: A total of 33 subjects with a median (IQR) smoking history of 34 (20-58) pack years were examined for nasal mucociliary clearance using a saccharine transit test, mucus properties using contact angle and sneeze clearability tests, and quantification of inflammatory and epithelial cells, IL-6 and IL-8 concentrations in nasal lavage fluid. Twenty quitters (mean age: 51 years, 9 male) were assessed at baseline, 1 month, 3 months and 12 months after smoking cessation, and 13 smokers (mean age: 52 years, 6 male) were assessed at baseline and after 12 months. Clinicaltrials.gov: NCT02136550. RESULTS: Smokers and quitters showed similar demographic characteristics and morbidities. At baseline, all subjects showed impaired nasal mucociliary clearance (mean 17.6 min), although 63% and 85% of the quitters demonstrated significant nasal mucociliary clearance improvement at 1 month and 12 months, respectively. At 12 months, quitters also showed mucus sneeze clearability improvement (∼26%), an increased number of macrophages (2-fold) and no changes in mucus contact angle or cytokine concentrations. CONCLUSION: This study showed that smoking cessation induced early improvements in nasal mucociliary clearance independent of mucus properties and inflammation. Changes in mucus properties were observed after only 12 months of smoking cessation.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Smoking/adverse effects , Smoking Cessation , Mucus/chemistry , Time Factors , Carbon Monoxide/analysis , Smoking/metabolism , Cell Count , Mucociliary Clearance , Longitudinal Studies , Interleukin-8/metabolism , Interleukin-6/metabolism , Nasal Lavage Fluid/chemistry , Cotinine/analysis , Inflammation/pathology , Nasal Mucosa/pathology
20.
Clin. biomed. res ; 36(3): 148-155, 2016. tab, graf
Article in Portuguese | LILACS | ID: biblio-831715

ABSTRACT

Introdução: O tecido adiposo é um importante órgão endócrino secretor de adipocinas como a interleucina-6 (IL-6), que estimula a produção de proteínas de fase aguda no fígado, conduzindo a um estado inflamatório subclínico associado ao surgimento de comorbidades presentes na obesidade, como a resistência à insulina (RI). O objetivo deste estudo foi avaliar a concentração de IL-6 em jovens obesos, com sobrepeso e de peso normal, correlacionando as concentrações dessa citocina com biomarcadores de RI. Métodos: Foi conduzido um estudo transversal que envolveu 149 indivíduos: 54 saudáveis (32 mulheres e 22 homens), 27 com sobrepeso (17 mulheres e 10 homens) e 68 obesos (41 mulheres e 27 homens). As medidas antropométricas e as concentrações de IL-6, insulina, hemoglobina glicada e glicose foram determinadas, assim como os cálculos do Modelo de Avaliação da Homeostase (HOMA) e da sensibilidade insulínica (SI). Resultados: Pacientes obesos mostraram níveis de IL-6, glicose, insulina e HOMA significativamente superiores e redução da SI quando comparados com pacientes de peso normal. Correlações positivas foram observadas entre IL-6, glicose, insulina e HOMA. Conclusão: Este estudo sugere que a IL-6 pode ter um papel-chave no desenvolvimento da RI em obesos e que o aumento de sua produção pode contribuir para a inflamação do tecido adiposo e interferir significativamente na atividade da insulina. Embora mais estudos clínicos sejam necessários para elucidar os reais mecanismos de interferência da IL-6 sobre a SI, sugere-se que essa citocina poderá ser, no futuro, uma determinação importante para avaliar e monitorar a RI em obesos jovens (AU)


Introduction: Adipose tissue is a major endocrine organ responsible for secretion of adipokines, such as interleukin-6 (IL-6), which stimulates the production of acute phase proteins in the liver, leading to a proinflammatory condition associated with the development of comorbidities in obesity, such as insulin resistance (IR). The aim of this study was to evaluate the IL-6 concentration in obese, overweight, and normal-weight young adults, correlating the concentrations of this cytokine with IR biomarkers. Methods: A cross-sectional study was conducted involving 149 subjects: 54 healthy subjects (32 women and 22 men), 27 overweight subjects (17 women and 10 men) and 68 obese subjects (41 women and 27 men). The anthropometric measures and IL-6, insulin, glucose, and glycated hemoglobin concentrations were determined, as well as HOMA and insulin sensitivity levels. Results: Obese patients showed significantly higher IL-6 levels of glucose, insulin, and HOMA and lower SI compared with normal-weight patients. Positive correlations were observed between IL-6, glucose, insulin, and HOMA. Conclusions: The present study suggests that IL-6 may have a key role in the development of IR in obese patients, and increasing its production can contribute to inflammation in adipose tissue and significantly interfere with insulin activity. Although further clinical studies are needed to elucidate the actual IL-6 interference mechanisms on SI, we believe that this cytokine may be an important factor to evaluate and monitor IR in obese young adults in the future (AU)


Subject(s)
Humans , Adult , Insulin Resistance/physiology , Interleukin-6/blood , Obesity/metabolism , Adipose Tissue/physiopathology , Biomarkers/blood , Body Weight , Insulin/blood , Insulin/metabolism , Interleukin-6/metabolism
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