Pro-inflammatory cytokines in patients with low back pain: A comparative study.

INTRODUCTION AND OBJECTIVES: There are controversial results regarding the value of serum IL-8 and TNFα in patients with non-specific low back pain. This study aimed to compare pro-inflammatory cytokines between patients with non-specific back pain and pain-free controls. MATERIALS AND METHODS: We conducted a case-control study including 106 participants: 46 patients with chronic non-specific low back pain (G1) and 60 pain-free controls (G0). The interleukin (IL-)6, IL-8, IL-17, IL-23, IL-22, and Tumor necrosis factor α (TNFα) were measured. We collected demographic and clinical data, including age, gender, low back pain duration and radicular pain. The pain degree was assessed using the Visual Analogic Scale. RESULTS: The mean age was 43.17±8.7 years in G1. Radicular pain was found in 37 cases with a Visual Analogic Scale of 3.03±2.5mm. The magnetic resonance imaging was performed in (G1), showing disk herniation and degenerative disk disease in 54.3% (n=25) and 45.7% of cases (n=21), respectively. The IL-8 was higher in G1 (18.84±44.64 versus 4.34±1.23pg/mL, p:0.033). IL-8 levels correlated with TNFα (0.942, p<10-3), IL-6 (0.490, p=0.011) and Visual Analogic ScaleRadicular-pain (r:0.297, p:0.047). IL-17 was higher in patients with restricted lumbar spine mobility (9.64±20.77 versus 1.19±2.54pg/mL, p:0.014). CONCLUSIONS: Our results provide evidence that IL-8 and TNFα play a role in low back pain and radicular pain due to disk degeneration or herniation. These findings could potentially be used by future studies to develop new non-specific low back pain therapeutic strategies.

Pro-inflammatory cytokines in patients with low back pain: A comparative study / Citoquinas proinflamatorias en pacientes con dolor lumbar: un estudio comparativo

Introduction and objectives: There are controversial results regarding the value of serum IL-8 and TNFα in patients with non-specific low back pain. This study aimed to compare pro-inflammatory cytokines between patients with non-specific back pain and pain-free controls. Materials and methods: We conducted a case–control study including 106 participants: 46 patients with chronic non-specific low back pain (G1) and 60 pain-free controls (G0). The interleukin (IL-)6, IL-8, IL-17, IL-23, IL-22, and Tumor necrosis factor α (TNFα) were measured. We collected demographic and clinical data, including age, gender, low back pain duration and radicular pain. The pain degree was assessed using the Visual Analogic Scale. Results: The mean age was 43.17±8.7 years in G1. Radicular pain was found in 37 cases with a Visual Analogic Scale of 3.03±2.5mm. The magnetic resonance imaging was performed in (G1), showing disk herniation and degenerative disk disease in 54.3% (n=25) and 45.7% of cases (n=21), respectively. The IL-8 was higher in G1 (18.84±44.64 versus 4.34±1.23pg/mL, p:0.033). IL-8 levels correlated with TNFα (0.942, p<10–3), IL-6 (0.490, p=0.011) and Visual Analogic ScaleRadicular-pain (r:0.297, p:0.047). IL-17 was higher in patients with restricted lumbar spine mobility (9.64±20.77 versus 1.19±2.54pg/mL, p:0.014). Conclusions: Our results provide evidence that IL-8 and TNFα play a role in low back pain and radicular pain due to disk degeneration or herniation. These findings could potentially be used by future studies to develop new non-specific low back pain therapeutic strategies.(AU)

Introducción y objetivos: Existen resultados controvertidos en cuanto al valor de la interleucina (IL) 8 y el factor de necrosis tumoral α (TNFα) séricos en pacientes con lumbalgia inespecífica. Este estudio tuvo como objetivo comparar las citoquinas proinflamatorias entre pacientes con dolor de espalda inespecífico y controles sin dolor. Materiales y métodos: Realizamos un estudio de casos y controles que incluyó a 106 participantes: 46 pacientes con dolor lumbar crónico inespecífico (G1) y 60 controles sin dolor (G0). Se midieron las IL-6, IL-8, IL-17, IL-23, IL-22 y el TNFα. Recopilamos datos demográficos y clínicos, incluidos la edad, el sexo, la duración del dolor lumbar y el dolor radicular. El grado de dolor se evaluó mediante la escala analógica visual. Resultados: La edad media fue de 43,17±8,7 años en G1. Se encontró dolor radicular en 37 casos con una escala analógica visual de 3,03±2,5mm. La resonancia magnética se realizó en G1, mostrando hernia discal y enfermedad discal degenerativa en el 54,3% (n=25) y el 45,7% de los casos (n=21), respectivamente. La IL-8 fue mayor en G1 (18,84±44,64 versus 4,34±1,23pg/ml, p=0,033). Los niveles de IL-8 se correlacionaron con TNFα (0,942, p<10−3), IL-6 (0,490, p=0,011) y escala visual analógicadolor radicular (r=0,297, p=0,047). IL-17 fue mayor en pacientes con movilidad restringida de la columna lumbar (9,64±20,77 versus 1,19±2,54pg/ml, p=0,014). Conclusiones: Nuestros resultados proporcionan evidencia de que la IL-8 y el TNFα juegan un papel en el dolor lumbar y en el dolor radicular debido a la degeneración o a hernia discal. Estos hallazgos podrían potencialmente ser utilizados por estudios futuros para desarrollar nuevas estrategias terapéuticas no específicas para el dolor lumbar.(AU)

Predictive capacity of IL-8 expression in head and neck squamous carcinoma patients treated with radiotherapy or chemoradiotherapy.

OBJECTIVE: To analyse the relationship between the transcriptional expression of interleukin-8 (IL-8) and response to treatment with radiotherapy or chemo-radiotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: Retrospective study from tumour biopsies obtained before a treatment with radiotherapy or chemo-radiotherapy in 87 patients with SCCHN. We had a sample of healthy mucosa in 35 cases. We determined the transcriptional expression of IL-8 with RT-PCR. The transcriptional expression of IL-8 was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: The transcriptional expression of IL-8 in tumour tissue was about 50 times higher than that in the samples of healthy mucosa. Patients with a high transcriptional expression of IL-8 (n = 56) had a 5-year local recurrence-free survival of 65.6%, and for patients with low expression (n = 31) it was 90.2% (P = 0.017). According to the results of a multivariate analysis, patients with high expression of IL-8 had a 4.1 higher risk of local recurrence of the tumour. CONCLUSIONS: SCCHN have a significant increase in transcriptional expression of IL-8 in relation to non-tumour tissue. Tumours with high IL-8 expression have an increased risk of local recurrence after treatment with radiotherapy or chemo-radiotherapy.

Capacidad predictiva de la expresión de IL-8 en pacientes con carcinomas escamosos de cabeza y cuello tratados con radioterapia o quimio-radioterapia / Predictive capacity of IL-8 expression in head and neck squamous carcinoma patients treated with radiotherapy or chemoradiotherapy

Objetivo: Analizar la relación entre la expresión transcripcional de interleucina-8 (IL-8) y la respuesta al tratamiento con radioterapia o quimio-radioterapia en pacientes con carcinoma escamoso de cabeza y cuello (CECC).Material y métodosEstudio retrospectivo realizado a partir de biopsias de tumor obtenidas de forma previa a un tratamiento con radioterapia o quimio-radioterapia en 87 pacientes con CECC. Se dispuso de una muestra de mucosa sana en 35 ocasiones. Se determinó la expresión transcripcional de la IL-8 mediante RT-PCR. Se categorizó el nivel de expresión transcripcional de IL-8 en función del control local de la enfermedad mediante un análisis de partición recursiva.ResultadosLa expresión transcripcional de IL-8 en el tejido tumoral fue unas 50 veces superior al de las muestras de mucosa sana. La supervivencia libre de recidiva local a los 5años para los pacientes con una expresión transcripcional elevada de IL-8 (n=56) fue del 65,6%, y para los pacientes con una expresión baja (n=31) del 90,2% (p=0,017). De acuerdo con los resultados de un análisis multivariante, los pacientes con unos niveles de expresión elevada de IL-8 contaron con un riesgo 4,1 veces superior de recidiva local de la enfermedad.ConclusionesLos CECC cuentan con un incremento significativo en los niveles de expresión transcripcional de la IL-8 en relación con el tejido no tumoral. Los tumores con unos niveles de expresión elevados de IL-8 tienen un incremento en el riesgo de sufrir una recidiva local del tumor tras un tratamiento con radioterapia o quimio-radioterapia. (AU)

Objective: To analyse the relationship between the transcriptional expression of interleukin-8 (IL-8) and response to treatment with radiotherapy or chemo-radiotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN).Material and methodsRetrospective study from tumour biopsies obtained before a treatment with radiotherapy or chemo-radiotherapy in 87 patients with SCCHN. We had a sample of healthy mucosa in 35 cases. We determined the transcriptional expression of IL-8 with RT-PCR. The transcriptional expression of IL-8 was categorized according to the local control of the disease with a recursive partitioning analysis.ResultsThe transcriptional expression of IL-8 in tumour tissue was about 50 times higher than that in the samples of healthy mucosa. Patients with a high transcriptional expression of IL-8 (n=56) had a 5-year local recurrence-free survival of 65.6%, and for patients with low expression (n=31) it was 90.2% (P=.017). According to the results of a multivariate analysis, patients with high expression of IL-8 had a 4.1 higher risk of local recurrence of the tumour.ConclusionsSCCHN have a significant increase in transcriptional expression of IL-8 in relation to non-tumour tissue. Tumours with high IL-8 expression have an increased risk of local recurrence after treatment with radiotherapy or chemo-radiotherapy. (AU)

Interleukin-8 is increased in chronic kidney disease in children, but not related to cardiovascular disease / A Interleucina-8 é aumentada na doença renal crônica em crianças, mas não se relaciona a doença cardiovascular

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.

Predictive capacity of IL-8 expression in head and neck squamous carcinoma patients treated with radiotherapy or chemoradiotherapy. / Capacidad predictiva de la expresión de IL-8 en pacientes con carcinomas escamosos de cabeza y cuello tratados con radioterapia o quimio-radioterapia.

OBJECTIVE: To analyse the relationship between the transcriptional expression of interleukin-8 (IL-8) and response to treatment with radiotherapy or chemo-radiotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: Retrospective study from tumour biopsies obtained before a treatment with radiotherapy or chemo-radiotherapy in 87 patients with SCCHN. We had a sample of healthy mucosa in 35 cases. We determined the transcriptional expression of IL-8 with RT-PCR. The transcriptional expression of IL-8 was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: The transcriptional expression of IL-8 in tumour tissue was about 50 times higher than that in the samples of healthy mucosa. Patients with a high transcriptional expression of IL-8 (n=56) had a 5-year local recurrence-free survival of 65.6%, and for patients with low expression (n=31) it was 90.2% (P=.017). According to the results of a multivariate analysis, patients with high expression of IL-8 had a 4.1 higher risk of local recurrence of the tumour. CONCLUSIONS: SCCHN have a significant increase in transcriptional expression of IL-8 in relation to non-tumour tissue. Tumours with high IL-8 expression have an increased risk of local recurrence after treatment with radiotherapy or chemo-radiotherapy.

Association of il-8 -251t>a (rs4073) polymorphism with susceptibility to gastric cancer: a systematic review and meta-analysis based on 33 case-control studies / Associação de polimorfismo IL-8 -251T> A (rs4073) com suscetibilidade ao câncer gástrico: uma revisão sistemática e meta-análise com base em 33 estudos caso controle

ABSTRACT BACKGROUND: The role of -251A>T polymorphism in the anti-inflammatory cytokine interleukin-8 (IL-8) gene in gastric cancer was intensively evaluated, but the results of these studies were inconsistent. OBJECTIVE: Therefore, we performed a meta-analysis to provide a comprehensive data on the association of IL-8 -251T>A polymorphism with gastric cancer. METHODS: All eligible studies were identified in PubMed, Web of Science, EMBASE, Wanfang and CNKI databases before September 01, 2019. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from a fixed effect or random effect model. RESULTS: A total of 33 case-control studies with 6,192 cases and 9,567 controls were selected. Overall, pooled data showed that IL-8 -251T>A polymorphism was significantly associated with an increased risk of gastric cancer under all five genetic models, i.e., allele (A vs T: OR=1.189, 95% CI 1.027-1.378, P=0.021), homozygote (AA vs TT: OR=1.307, 95% CI 1.111-1.536, P=0.001), heterozygote (AT vs TT: OR=1.188, 95% CI 1.061-1.330, P=0.003), dominant (AA+AT vs TT: OR=1.337, 95% CI 1.115-1.602, P=0.002) and recessive (AA vs AT+TT: OR=1.241, 95% CI 1.045-1.474, P=0.014). The stratified analysis by ethnicity revealed an increased risk of gastric cancer in Asians and mixed populations, but not in Caucasians. Moreover, stratified by country found a significant association in Chinese, Korean and Brazilian, but not among Japanese. CONCLUSION: This meta-analysis suggests that the IL-8 -251T>A polymorphism is associated with an increased risk of gastric cancer, especially by ethnicity (Asian and mixed populations) and country (Chinese, Korean and Brazilian).

RESUMO CONTEXTO: O papel do polimorfismo -251A>T no gene anti-inflamatório citocina interleucina-8 (IL-8) no câncer gástrico foi intensamente avaliado, mas os resultados desses estudos foram inconsistentes. OBJETIVO: Portanto, realizamos uma meta-análise para fornecer dados abrangentes sobre a associação de IL-8 -251T>A polimorfismo com câncer gástrico. MÉTODOS: Todos os estudos elegíveis foram identificados nos bancos de dados PubMed, Web of Science, EMBASE, Wanfang e CNKI antes de 01 de setembro de 2019. As relações de probabilidades agrupadas (ORs) com intervalos de confiança de 95% (IC) foram derivadas de um modelo de efeito fixo ou efeito aleatório. RESULTADOS: Foram selecionados 33 estudos de controle de caso com 6.192 casos e 9.567 controles. No geral, dados agrupados mostraram que o polimorfismo IL-8 -251T>A foi significativamente associado a um risco aumentado de câncer gástrico em todos os cinco modelos genéticos, isto é, alelo (A vs T: OR=1,189; 95% CI 1,027-1,378; P=0,021), homozigoto (AA vs TT: OR=1,307; 95% CI 1,111-1,536; P=0,001), heterozigoto (AT vs TT: OR=1,188; 95% CI 1,061-1,330; P=0,003), dominante (AA+AT vs TT: OR=1,337; 95% CI 1,115-1,602; P=0,002) e recessivo (AA vs AT+TT: OR=1,241; 95% CI 1,045-1,474; P=0,014). A análise estratificada por etnia revelou um risco aumentado de câncer gástrico em asiáticos e populações mistas, mas não em caucasianos. Além disso, estratificado por país. Encontrou-se uma associação significativa em chineses, coreanos e brasileiros, mas não entre os japoneses. CONCLUSÃO: Esta meta-análise sugere que o polimorfismo IL-8 -251T>A está associado a um risco aumentado de câncer gástrico, especialmente por etnia (populações asiáticas e mistas) e por país (chinês, coreano e brasileiro).

Comparison of Plasma Cytokine Levels before and after Treatment with Rituximab in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus-Associated Polyautoimmunity / Comparación de citocinas plasmáticas antes y después del tratamiento con rituximab en pacientes con artritis reumatoide y lupus eritematoso sistémico asociado a poliautoinmunidad

Introducción: La coexistencia de más de una enfermedad autoinmune (EAI) en un paciente se conoce como poliautoinmunidad (PAI) y se observa en el 35% de los pacientes con EAI. La eliminación de linfocitos B usando rituximab (RTX) controla la actividad de diferentes EAI. En el lupus eritematoso sistémico (LES) y en PAI no es clara la producción de citocinas por los linfocitos B. Métodos: Estudio exploratorio. Se obtuvo plasma de 11 pacientes con artritis reumatoide (AR) y poliautoinmunidad asociada a LES (PAILES) antes y después de rituximab (i. e., 6 meses). Como controles se utilizaron ocho individuos sanos. Las citocinas se midieron por ELISA (IFN-a, TGF-pl) o Cytometnc Bead Array (TNF-a, IL-ip, IL-ó, IL-8, IL-10, IL-12p7O). Resultados: Previo a RTX, IL-ó se encontró elevada únicamente en AR, mientras que IL-8 lo estuvo en AR y en PAILES, comparados con controles. Después de RTX se encontró una disminución significativa de IL-ó en AR y de IL-8 en PAILES. Las concentraciones de otras citocinas medidas fueron similares (IFN-a, TGF-B1) o se encontraron por debajo de límite de detección (TNF-a, IL-1[3, IL-10, IL-12p7O), tanto en pacientes como en controles. Conclusión: Los datos resaltan la importancia de la secreción de citocinas por los linfocitos B y sugieren un rol diferencial en cada patología. El incremento de IL-8 previo a RTX en ambos grupos y la reducción después de la terapia en PAILES respaldan el potencial de la IL-8 como objetivo terapéutico. La heterogeneidad de la población de pacientes con PAI reafirma la importancia de la selección de subgrupos específicos en estudios futuros.

Introduction: Coexistence of more than one autoimmune disease (AD) in a single patient is known as polyautoimmunity, and may be seen in up to 35% of patients with ADs. The elimination of B-cells using Rituximab (RTX) improves clinical status in different ADs. The role of cytokine production by B-cells is unclear in systemic lupus erythematosus (SLE) and polyautoimmunity. Methods: As an exploratory study, plasma from 11 patients with either rheumatoid arthritis (RA) or SLE-associated polyautoimmunity was assessed prior and 6 months after therapy with RTX. Eight healthy individuáis were used as Controls. Cytokine levels were measured using ELISA (IFN-a and TGF-61) or Cytometric Bead Array (TNF-a, IL-1

Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis / Variantes no gene da interleucina 8 e a resposta a broncodilatadores inalatórios na fibrose cística

Abstract Objective: Interleukin 8 protein promotes inflammatory responses, even in airways. The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators. Thus, this study analyzed the interleukin 8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to inhaled bronchodilators in cystic fibrosis patients. Methods: Analysis of interleukin 8 gene variants was performed by restriction fragment length polymorphism of polymerase chain reaction. The association between spirometry markers and the response to inhaled bronchodilators was evaluated by Mann-Whitney and Kruskal-Wallis tests. The analysis included all cystic fibrosis patients, and subsequently patients with two mutations in the cystic fibrosis transmembrane conductance regulator gene belonging to classes I to III. Results: This study included 186 cystic fibrosis patients. There was no association of the rs2227307 variant with the response to inhaled bronchodilators. The rs2227306 variant was associated with FEF50% in the dominant group and in the group with two identified mutations in the cystic fibrosis transmembrane conductance regulator gene. The rs4073 variant was associated with spirometry markers in four genetic models: co-dominant (FEF25-75% and FEF75%), dominant (FEV1, FEF50%, FEF75%, and FEF25-75%), recessive (FEF75% and FEF25-75%), and over-dominant (FEV1/FVC). Conclusions: This study highlighted the importance of the rs4073 variant of the interleukin 8 gene, regarding response to inhaled bronchodilators, and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene.

Resumo Objetivo: A proteína interleucina 8 promove respostas inflamatórias, o que inclui sua atuação nas vias aéreas. A presença de variantes no gene da interleucina 8 causa respostas inflamatórias alteradas e possivelmente respostas variadas ao uso de broncodilatadores inalatórios. Assim, este estudo analisou as variantes da interleucina 8 (rs4073, rs2227306, rs2227307) e sua associação à resposta a broncodilatadores inalatórios em pacientes com fibrose cística. Métodos: Foi feita análise das variantes genéticas da interleucina 8 por restriction fragment length polymorphism da reação em cadeia da polimerase. A associação entre os marcadores da espirometria e a resposta a broncodilatadores inalatórios foi feita pelos testes de Mann-Whitney e Kruskal-Wallis. A análise incluiu todos os pacientes com fibrose cística e posteriormente pacientes com duas mutações no gene cystic fibrosis transmembrane conductance regulator pertencentes às Classes I a II. Resultados: Este estudo incluiu 186 pacientes com fibrose cística. Não houve associação da variante rs2227307 à resposta a broncodilatadores inalatórios. A variante rs2227306 foi associada a FEF50% no grupo dominante e no grupo com duas mutações identificadas no gene cystic fibrosis transmembrane conductance regulator. A variante rs4073 foi associada a marcadores da espirometria em quatro modelos genéticos: codominante (FEF25-75% e FEF75%), dominante (VEF1, FEF50%, FEF75% e FEF25-75%), recessivo (FEF75% e FEF25-75%) e overdominante (VEF1/CVF). Conclusões: Este estudo destaca, principalmente, a importância da variante rs4073 do gene da interleucina 8, na resposta a broncodilatadores inalatórios, concomitantemente ao genótipo das mutações no gene cystic fibrosis transmembrane conductance regulator.

Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis.

OBJECTIVE: Interleukin 8 protein promotes inflammatory responses, even in airways. The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators. Thus, this study analyzed the interleukin 8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to inhaled bronchodilators in cystic fibrosis patients. METHODS: Analysis of interleukin 8 gene variants was performed by restriction fragment length polymorphism of polymerase chain reaction. The association between spirometry markers and the response to inhaled bronchodilators was evaluated by Mann-Whitney and Kruskal-Wallis tests. The analysis included all cystic fibrosis patients, and subsequently patients with two mutations in the cystic fibrosis transmembrane conductance regulator gene belonging to classes I to III. RESULTS: This study included 186 cystic fibrosis patients. There was no association of the rs2227307 variant with the response to inhaled bronchodilators. The rs2227306 variant was associated with FEF50% in the dominant group and in the group with two identified mutations in the cystic fibrosis transmembrane conductance regulator gene. The rs4073 variant was associated with spirometry markers in four genetic models: co-dominant (FEF25-75% and FEF75%), dominant (FEV1, FEF50%, FEF75%, and FEF25-75%), recessive (FEF75% and FEF25-75%), and over-dominant (FEV1/FVC). CONCLUSIONS: This study highlighted the importance of the rs4073 variant of the interleukin 8 gene, regarding response to inhaled bronchodilators, and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene.

Expressão dos receptores Toll-like em carcinoma espinocelular de orofaringe / Expression of Toll-like receptor in oropharynx squamous cell carcinoma

Nos últimos anos, notou-se aumento da incidência de carcinoma espinocelular de orofaringe (CECOF) associado ao HPV. Sabe-se que CECOF associado ao HPV apresenta melhor prognóstico do que CECOF não infectado por HPV. Inúmeros estudos em carcinoma cervical demonstram alterações de TLRs, isto provavelmente devido às associações das oncoproteínas E6 e E7 com estes receptores. Em humanos, existem 10 TLRs identificados, os quais colaboram na resposta imune contra bactérias, fungos e vírus, bem como colaboram na promoção ou regressão do tumor. Esta influência do TLR na carcinogênese tem sido alvo de inúmeros estudos devido à ligação entre inflamação e o câncer. O presente trabalho teve como objetivo verificar diferenças na expressão e função de receptores Toll-like em carcinoma espinocelular de orofaringe (CECOF). Para tal, foram utilizados trinta e sete espécimes diagnosticados como CECOF e a expressão imuno-histoquímica das proteínas p16 e TLR4 analisadas. Duas linhagens de CECOF HPV16 + e duas CECOF HPV-. foram utilizadas para análise da expressão de TLR1-10, IL-6 e IL-8, por qPCR. A detecção dos principais TLRs (TLR1, TLR2, TLR6 e TLR4) foi feita por citometria de fluxo. Para ativação da via de sinalização de TLR2, e posterior análise da expressão de IL6 e IL8, as células foram estimuladas com peptidoglicano. Para verificar a expressão e função de TLR4, as células foram estimuladas com LPS e LPS UP para posterior análise de IL-6 e IL-8, por ELISA. Os resultados demonstraram diferenças na expressão gênica de TLR1 e TLR6 entre as linhagens HPV- e o grupo HPV+ e diferenças na expressão proteica de TLR9. TLR2 apresentou...

The incidence of HPV- associated oropharynx squamous cell carcinoma (OPSCC) has increased in recent years. HPV- associated OPSCC has a better prognosis than OPSCC not infected with HPV. In cervical carcinoma, HPV oncoproteins E6 and E7 influence the expression of Toll-like receptors (TLR). To date, 10 TLRs have been identified in humans and many are important for the detection of bacteria, fungi and viruses, as well as regression and tumor promotion. This influence of TLR in carcinogenesis has been the subject of numerous studies, due to the connection between inflammation and cancer. This study aimed to determine differences in the expression and function of Toll-like receptor in OPSCC. Thirty-seven tumours were selected and immunohistochemistry for p16 and TLR4 was performed. Two HPV16-associated OPSCC and two OPSCC not associated to HPVcell lines were used. qPCR was performed to analyze the expression of TLR1-10, IL-6 and IL-8. The detection of the main TLRs (TLR1, TLR2, TLR6 and TLR4) was performed by flow cytometry. For activation of the TLR2-signaling pathway and subsequent analysis of IL6 and IL8 expression, cells were stimulated with peptidoglycan. To verify the expression and function TLR4 cells were stimulated with LPS and LPS UP and subsequent analysis of IL-6 and IL-8 by ELISA. The results showed differences in the...

Soro urêmico inibe a expressão in vitro da quimiocina SDF-1: possível impacto da toxicidade urêmica na lesão endotelial / Uremic serum inhibits in vitro expression of chemokine SDF-1: impact of uremic toxicity on endothelial injury

Introdução: A disfunção endotelial é importante na patogênese da doença cardiovascular (DCV) relacionada à doença renal crônica (DRC). Stromal cell-derived factor-1 (SDF-1) é uma quimiocina que mobiliza células endoteliais progenitoras (EPC) e em conjunto com a interleucina-8 (IL-8) podem ser usadas como marcadores de reparo e lesão tecidual. Objetivo: Neste trabalho, foi investigado o efeito do meio urêmico na expressão de SDF-1 e IL-8 in vivo e in vitro. Métodos: A inflamação sistêmica foi avaliada por meio da proteína C-reativa (PCR) e interleucina-6 (IL-6). IL-8 e SDF-1 foram avaliados por ELISA como marcadores de disfunção endotelial e reparo tecidual, respectivamente. Os estudos in vitro foram realizados em células endoteliais umbilicais humanas (HUVEC) expostas ao meio urêmico ou saudável. Resultados: Foram incluídos nesse estudo 26 pacientes em hemodiálise (HD) (17 ± 3 meses em diálise, 52 ± 2 anos, 38% homens e 11% diabéticos). As concentrações séricas de PCR, IL-6, SDF-1 e IL-8 foram 4,9 ± 4,8 mg/ml, 6,7 ± 8,1 pg/ml, 2625,9 ± 1288,6 pg/ml e 128,2 ± 206,2 pg/ml, respectivamente. Houve correlação positiva entre PCR e IL-6 (ρ = 0,57; p < 0,005) e entre SDF-1 e IL-8 (ρ = 0,45; p < 0,05). Os resultados in vitro demonstraram que a expressão de SDF-1 pelas HUVEC após 6 horas de tratamento com meio urêmico é menor comparada ao tratamento com meio saudável (p < 0,05). Após 12 horas de tratamento, ocorreu aumento de IL-8 quando as HUVECs foram expostas ao meio urêmico (p < 0,005). Conclusão: Sugerimos que SDF-1 e IL-8 nos pacientes em HD podem ser usados para mensurar a extensão do dano e consequente ativação vascular na uremia. .

Introduction: Endothelial dysfunction is important in the pathogenesis of cardiovascular disease (CVD) related to chronic kidney disease (CKD). Stromal cell-derived factor-1 (SDF-1) is a chemokine which mobilizes endothelial progenitor cells (EPC) and together with interleukin-8 (IL-8) may be used as markers of tissue injury and repair. Objective: This study investigated in vivo and in vitro the effect of uremic media on SDF-1 and IL-8 expression. Methods: Systemic inflammation was assessed by C-reactive protein (CRP) and interleukin-6 (IL-6). IL-8 and SDF-1 were measured as markers of endothelial dysfunction and tissue repair, respectively, by ELISA. In vitro studies were performed on human umbilical vein endothelial cells (HUVEC) exposed to healthy or uremic media. Results: The study included 26 hemodialysis (HD) patients (17 ± 3 months on dialysis, 52 ± 2 years, 38% men and 11% diabetic). Serum concentrations of CRP, IL-6, SDF-1 and IL-8 were 4.9 ± 4.8 mg/ml, 6.7 ± 8.1 pg/ml, 2625.9 ± 1288.6 pg/ml and 128.2 ± 206.2 pg/ml, respectively. There was a positive correlation between CRP and IL-6 (ρ = 0.57, p < 0.005) and between SDF-1 and IL-8 (ρ = 0.45, p < 0.05). In vitro results showed that after 6 hours treatment, SDF-1 expression by HUVEC treated with uremic media is lower compared to cells treated with healthy media (p < 0.05). After 12 hours of treatment there was an increase in IL-8 when HUVECs were exposed to uremic media (p < 0.005). Conclusion: We suggest that SDF-1 and IL-8 in HD patients can be used to measure the extent of damage and subsequent vascular activation in uremia. .

Expresión del fenotipo Duffy negativo en mujeres afrodescendientes y su relación con la preeclampsia / Expression of the Duffy negative phenotype in women of African descent and their relation to pre-eclampsia

La preeclampsia (PE) es una complicación del embarazo que trae consigo algunas consecuencias negativas para la madre y el feto: en la madre provoca principalmente hipertensión y proteinuria, mientras que en el feto puede presentarse trombocitopenia, alteración en el desarrollo del sistema nervioso central y circulatorio, y restricción del crecimiento intrauterino, lo cual se considera el factor de riesgo principal de muerte fetal en nacimientos producto de una PE severa. En la preeclampsia se presenta una disfunción endotelial relacionada con placentación anormal, estado de estrés oxidativo y proceso inflamatorio sistémico, que lleva a la activación de neutrófilos y monocitos. Se ha considerado a la interleucina-8 (IL-8) como un posible candidato desencadenante por ser quimioatrayente y activador de leucocitos; en la circulación sanguínea, la IL-8 se une a un receptor de quimiocina multiespecífico de alta afinidad denominado DARC, que es idéntico al antígeno del grupo sanguíneo Duffy. Este receptor regula los niveles plasmáticos de IL-8, uniéndose a esta quimiocina, pero cuando hay una mutación en la región promotora del gen se altera la expresión de DARC, lo que conlleva a que la IL-8 de los factores genéticos involucrados en la activación de los neutrófilos y de los monocitos, y por ende, en la disfunción endotelial presentada durante este síndrome hipertensivo, especialmente en la población afrodescendiente.

Preeclampsia (PE) is a complication of pregnancy that brings some negative consequences for both mother and fetus. It specially causes hypertension and proteinuria in mothers; while in fetuses it causes thrombocytopenia, development alterations of the central nervous and circulatory system; also intrauterine growth restriction may occur. This last factor is regarded as the main risk factor for fetal death in births as a result of severe PE. There is endothelial dysfunction in preeclampsia related to abnormal placentation, state of oxidative stress and systemic inflammatory process that leads to the activation of neutrophils and monocytes. Interleukin-8 (IL-8) is considered as a possible trigger candidate, since this chemokine is a chemoattractant and leukocyte activator. In the bloodstream, interleukin-8 binds to a high affinity multispecific-chemokine receptor called DARC, which is identical to the Duffy blood group antigen. This receptor regulates plasma levels of IL-8 by binding to chemokine. But, when there is a mutation in the gene promoter region, DARC expression is altered, and IL-8 inefficiently binds to receptor. This mutation results in Duffy negative phenotype, which is present in most of African descendants. This literature review is intended to address the role of IL-8 as neutrophil chemo-attractant, the importance of Duffy blood system and the possible association between ethnicity and preeclampsia.

Valor prognóstico dos polimorfismos fincionais nos genes da mmp-1, mmp-13 e il-8 no carcinoma epidermóide oral e de orofaringe / Fincionais prognostic value of polymorphisms in the genes of MMP-1, MMP-13 and IL-8 in oral squamous cell carcinoma and oropharyngeal

Tumores malignos têm a habilidade de invadir tecidos normais e de se espalharem para sítios anatômicos distantes, originando a metástase, o maior fator de mortalidade do câncer. As metaloproteinases de matriz (MMP)-l e MMP-13 têm sido associadas à invasão tumoral e à metástase, pois a MMP-1 degrada colágeno tipo I, que é o substrato mais abundante no estroma tumoral e a MMP-13 degrada colágeno tipo IV, dentre outros, que está presente na membrana basal dos vasos. Pesquisas mostram que a IL-8 é um potente fator angiogênico e está associada ao crescimento tumoral, à metástase e ao pobre prognóstico do câncer. O presente trabalho se propõe a verificar a existência e a frequência dos polimorfismos nos genes das MMPs-1 (rs2071230 e rs470558), -13 (rs2252070) e da IL-8 (rs4073 e rs2227532) e investigar o possível valor prognóstico dos mesmos em uma série de casos de carcinoma epidermóide oral e de orofaringe (CEOO). Foram genotipados por meio de PCR em tempo real 98 amostras de pacientes com carcinoma epidermóide e 134 amostras controle. Todos os polimorfismos estavam em equilíbrio de Hardy-Weinberg, exceto o SNP IL-8 (rs2227532). O genótipo homozigoto polimórfico GG da MMP-1 (rs2071230) revelou ser um fator de risco pouco mais de 8 vezes para o desenvolvimento do carcinoma epidermóide, enquanto o genótipo polimórfico GG da MMP-13 (rs2252070) diminuiu o risco de desenvolver CEOO em aproximado de 3 vezes. Verificou-se diferença na distribuição dos genótipos em relação à localização da lesão, sendo o genótipo CC da MMP-1 (rs470558) mais frequente em lesões intraorais e o CT em orofaringe e o genótipo TT da IL-8 (rs4073) mais comum em lesões intraorais e com estadiamento clínico III e IV. Os indivíduos portadores do genótipo GG da MMP-13 (rs2252070) apresentaram menor tempo de sobrevida livre de doença e sobrevida global. Conclui-se que o SNP (rs2252070) da MMP-13 possui valor prognóstico em pacientes com carcinoma epidermóide oral e de orofaringe.

Malignant tumors have the ability to invade normal tissues and spread to distant anatomic sites, leading to metastasis, the whole factor for cancer mortality. Matrix metalloproteinases (MMP)-l and MMP-13 have been associated with tumor invasion and metastasis because MMP-1 degrades type I collagen, which is the most abundant substrate in the tumor stroma and MMP-13 degrades type IV collagen, among others, that is present in the basement membrane of the vessels. Research shows that IL-8 is a potent angiogenic factor and is associated with tumor growth, metastasis and poor prognosis of cancer. This study aims to verify the existence and frequency of polymorphisms in genes of MMP-1 (rs2071230 and rs470558), -13 (rs2252070) and IL-8 (rs4073 and rs2227532) and investigate the possible prognostic value of the same in cases of squamous cell carcinoma. Ninety eight samples from patients with oral and oropharyngeal squamous cell carcinoma and 134 control samples were genotyped by real-time PCR. All polymorphisms were in Hardy-Weinberg equilibrium, except SNP (rs2227532) of IL-8. The polymorphic homozygote genotype GG of MMP-1 (rs2071230) was found to be a risk factor just over 8 times for the development of oral and oropharyngeal squamous cell carcinoma, while the GG genotype polymorphism of MMP-13 (rs2252070) showed a protective effect of approximately 3 times. CC genotype of MMP-1 (rs470558) was most frequent in intraoral and CT in oropharyngeal lesions. TT genotype of the IL-8 (rs4073) was most common in intraoral lesions and III and IV clinical staging. Patients with GG genotype of MMP-13 (rs2252070) had fewer disease-free survival and overall survival. We conclude that the SNP (rs2252070) of MMP-13 has prognostic value in patients with oral and oropharyngeal squamous cell carcinoma.

Valor prognóstico dos polimorfismos funcionais nos genes da mmp-1, mmp-13 e IL-8 no carcinoma epidermóide oral e de orofaringe / Prognostic value of functional polymorphisms in the mmp-1, mmp-13 and IL-8 genes in oral and oropharyngeal squamous cell carcinoma

Tumores malignos tem a habilidade de invadir tecidos normais e de se espalharem para sítios anatômicos distantes, originando, a metástase o maior fator de mortalidade do câncer. As metaloproteinases de matriz (MMP)-1 e MMP-13 tem sido associada a invasão tumoral e a metástase, pois a MMP-1 degrada colágeno tipo I, que é o substrato mais abundante no estroma tumoral e a MMP-13 degrada coágeno tipo IV, dentre outros , que está presente na membrana basal dos vasos. Pesquisas mostram que a IL-8 é um potente fator angiogênico e está associada ao crescimento tumoral, à metástase e ao pobre prognóstico do câncer. O presente trabalho se propõe a verificar a existência e a frequências dos polimorfismos nos genes das MMPs-1(rs2071230 e rs470558), -13(rs2252070) e da IL-8 (rs4073 e rs2227532) e investigar o possivel valor prognósticos dos mesmo em uma serie de casos de carcinoma epidermoide oral e de orofaringe(CEOO). Foram genotipados por meio de PCR em tempo real 98 amostra de pacientes com carcinoma epidermóide e 134 amostras controle (AU).

Abnormal spontaneous interleukin 8 receptor expression: a brief report of two cases / Expressão espontânea anômala do receptor de interleucina 8: um breve relato de dois casos

Interleukin 8 (CXCL8) is an autocrine chemokine specific for the chemoattraction and activation of granulocytes, NKT cells and T lymphocytes. Patients with tuberculosis and latent Mycobacterium tuberculosis infection were assessed for the spontaneous expression of CXCR1 (CD128) and CXCR2 on lymphocytes and monocytes. Compared with ex vivo profiles, increased spontaneous CXCR2 expression and normal CXCR1 expression were found on lymphocytes in two out of 59 individuals. Monocytes showed normal ex vivo profiles for both receptors. After stimulation with purified protein derivative, the in vitro levels of CXCL8 were below the median levels of all patients with prior tuberculosis. Spontaneous CXCR2 modulation did not cause notable variation in the in vitro levels of CXCL8.

Interleucina 8 (CXCL8) é quimiocina autócrina específica para atração e ativação de granulócitos, assim como NKT e linfócitos T. Pacientes com infecção por Mycobacterium tuberculosis e latentes foram recrutados para comparar expressão espontânea dos receptores CXCR1 (CD128) e CXCR2 nos mononucleares. Comparado com perfis ex vivo dos linfócitos, observou-se aumento em CXCR2; porém, expressão normal de CXCR1 em dois dos 59 indivíduos. Monócitos mostraram perfis ex vivo normais; após estimulação específica in vitro das citocinas estudadas com extrato bruto total, não se encontrou correspondência na anomalia observada ex vivo. Modulação espontânea de CXCR2 não causou grande variação in vitro nos níveis de CXCL8.

Investigação comparativa de dados clínicos e microbiológicos entre indivíduos geneticamente suscetíveis e não suscetíveis à periodontite / Clinical and microbiological data investigation from individuals genetically susceptible and non-susceptible to periodontitis

A Doença Periodontal (DP) tem caráter multifatorial, com influência da presença de microrganismos periodontopatogênicos, suscetibilidade genética do hospedeiro, entre outros. O tecido periodontal inflamado produz dentre outras citocinas, a Interleucina 8 (IL-8). Na literatura científica há informações conflitantes acerca dos níveis de IL-8 em fluido crevicular gengival de pacientes com e sem DP. Estudos prévios realizados por nosso grupo identificaram que pacientes carregando o haplótipo ATC/TTC no gene IL8 foram 2 vezes mais suscetíveis à DP e que esses pacientes mesmo com menor desafio microbiano, pareciam desenvolver a DP mais exacerbadamente comparados aos indivíduos considerados não suscetíveis à DP pela ausência daquele haplótipo. Como esses resultados foram obtidos de um estudo clínico, estudos in vitro se mostraram necessários para investigar a funcionalidade dos haplótipos no gene IL8. O objetivo deste trabalho foi verificar na literatura científica se os níveis de IL-8 estão aumentados ou não mediante a presença da DP e se, por meio de ensaios in vitro controlados, os mencionados haplótipos no gene IL8 podem influenciar a funcionalidade e expressão deste e outros genes importantes para a resposta imune. Realizamos uma criteriosa revisão sistemática da literatura seguida de meta-análise enfocando a quantificação de mRNA e proteína IL-8 em tecido gengival, saliva e fluido crevicular gengival (FCG) de pacientes com DP comparados a indivíduos periodontalmente saudáveis. Verificamos maior expressão gênica de IL8 e da proteína IL-8 nos tecidos gengivais de pacientes com DP, enquanto níveis proteicos de IL-8 mostraram níveis variáveis na saliva e FCG. Também investigamos em células isoladas do sangue periférico de pacientes carregando diferentes haplótipos no gene IL8, a possível influência destes na expressão de genes do sistema imune. A funcionalidade destes haplótipos no gene IL8 foi também investigada após edição genética em linhagem celular por meio do sistema CRISPR-CAS9 seguida de recombinação homóloga. Conjuntamente observamos que perante estímulos microbianos o haplótipo ATC/TCC foi associado à maior expressão gênica e funcionalidade do gene IL8 em comparação ao outro haplótipo ATT/TCC. Como conclusão geral notou-se que em tecido gengival há concordância na literatura sobre maiores níveis de mRNA e proteicos de IL-8 associados à DP, e que o haplótipo no gene IL8 previamente associado com suscetibilidade à DP mostrou-se funcional influenciando a expressão gênica

Periodontal disease (PD) is a multifactorial disease, influenced by the periodontopathogenic microorganisms' presence, host genetic susceptibility, among others. The inflamed periodontal tissue produces amongst other cytokines the Interleukin8 (IL-8). In the scientific literature there are conflicting information about the IL-8 levels in gingival crevicular fluid of patients with and without DP. Previous studies of our group found that patients carrying the haplotype ATC/TTC in IL8 gene were 2 times more susceptible to PD and these same patients with lower microbial challenge develop PD more exaggeratedly compared to individuals considered not susceptible to PD by absence of that haplotype. As these results were obtained from a clinical study, in vitro studies are necessary to investigate the functionality of the IL8 gene haplotypes. The objective of this study was to investigate whether IL-8 levels are increased or not by the presence of PD and, through controlled in vitro assays, the aforementioned haplotypes in IL8 gene can influence the functionality and expression of this and other important genes to the immune response. We conducted a rigorous literature systematic review followed by meta-analysis focusing on the mRNA and IL-8 protein quantification in gingival tissue, saliva and gingival crevicular fluid (GCF) of patients with PD compared to periodontally healthy individuals. We found a higher IL8 gene expression and IL-8 protein in the gingival tissues of PD patients, whereas protein levels of IL-8 showed varying levels in GCF and saliva. We also investigated cells from the patient's peripheral blood carrying different haplotypes in IL8 gene, their possible influence on the expression genes of the immune system. The functionality of these haplotypes in IL8 gene was also investigated after genetic edition in cell line using CRISPR-CAS9 followed by homologous recombination system. It was observed that against microbial stimuli the ATC/TTC haplotype was associated with increased gene expression and function of the IL8 gene compared to the ATT/TCC haplotype. As a general conclusion it was noted that in gingival tissue there is an agreement in the literature on higher levels of mRNA and protein for IL-8 associated with PD, and that the IL8 haplotype previously associated with susceptibility to chronic periodontitis proved functional, influencing gene expression

Polimorfismo da Interleucina-8 -251T>A e Helicobacter pylori / Interleukin-8 -251T>A polymorphism and Helicobacter pylori

Introdução: o Helicobacter pylori é um importante patógeno associado ao desenvolvimento de gastrite crônica, úlcera péptica e doenças gástricas. Vários autores relataram que a infiltração de células inflamatórias, incluindo neutrófilos, é um traço da patologia da mucosa gástrica associada com a infecção. Há evidências de que a inflamação está associada à gravidade das lesões gástricas. A interleucina 8 (IL-8), um membro da família das citocinas, é um ativador quimiotático de neutrófilos e linfócitos e tem sido descrito que o aumento dos níveis de IL-8 na mucosa gástrica pode estar associado com a infecção por H.pylori. Objetivos: os objetivos deste trabalho foram (i) caracterizar o polimorfismo da Interleucina-8 -251T>A (ii) e verificar a possível relação entre este polimorfismo e infecção por H.pylori. Métodos: cento e sessenta pacientes sintomáticos (com idade média de 48,7 anos) participaram do estudo: 107 pacientes positivos para H.pylori e 53 negativos, previamente diagnosticados por PCR. Os genótipos da IL-8 -251 T>A foram determinados através da reação em cadeia da polimerase (PCR) e utilização de enzimas de restrição (RFLP). Resultados e Conclusões: nossos resultados indicam que não há associação entre o polimorfismo da IL-8 -251 T>A e a infecção por H.pylori ou pelo gênero dos pacientes.

Background: Helicobacter pylori is an important pathogen associated with the development of chronic gastritis, peptic ulcer disease and gastric disease. Several authors reported that the infiltration of inflammatory cells, including neutrophils is the trace of the pathology of gastric mucosa, associated with the infection. There is high evidence that inflammation is associated with severity of gastric lesions. Interleukin-8 (IL-8), a member of cytokines family, is an activator and chemoattractant of neutrophils and lymphocytes. It has been reported that increased gastric mucosal levels of IL-8 is associated with H. pylori infection. Objective: the objectives of this paper were (i) characterize Interleukin-8 -251T>A polymorphism and (ii) to examine the possible relationship between this polymorphism and the H. pylori infection. Methods: one hundred and sixty patients, (with a mean age 48.7 years) presenting recurrent abdominal pain participated in the study: 107 H. pylori positives and 53 H. pylori negatives previously diagnosed by PCR. IL8 -251T>A genotypes were determined using a polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results and Conclusions: our findings indicate that there is no association of IL-8 -251T>A with H. pylori-infected patients or gender of these patients and these conclusions were consistent with other reports from different population samples.

Determination of strains of Helicobacter pylori and of polymorphism in the interleukin-8 gene in patients with stomach cancer / Determinação das cepas do Helicobacter pylori e do polimorfismo do gene da interleucina-8 em pacientes com câncer gástrico

CONTEXT: Gastric neoplasia is the second most common cause of death by cancer in the world and H. pylori is classified as a type I human carcinogen by the World Health Organization. However, despite the high prevalence of infection by H. pylori around the world, less than 3 percent of individuals carrying the bacteria develop gastric neoplasias. Such a fact indicates that evolution towards malignancy may be associated with bacterial factors in the host and the environment. OBJECTIVES: To investigate the association between polymorphism in the region promoting the IL-8 (-251) gene and the H. pylori genotype, based on the vacA alleles and the presence of the cagA gene, using clinical and histopathological data. METHODS: In a prospective study, a total of 102 patients with stomach cancer and 103 healthy volunteers were analysed. Polymorphism in interleukin 8 (-251) was determined by the PCR-restriction fragment length polymorphism reaction and sequencing. PCR was used for genotyping the vacA alleles and the cagA in the bacterial strains PCR. Gastric biopsies were histologically assessed. RESULTS: The H. pylori serology was positive for 101 (99 percent) of all patients analysed, and 98 (97 percent) of them were colonized by only one strain. In patients with monoinfection, 82 (84 percent) of the bacterial strains observed had the s1b/m1 genotype. The cagA gene was detected in 74 (73 percent) of patients infected by H. pylori. The presence of the cagA gene was demonstrated as associated with the presence of the s1b/m1 genotype of the vacA gene (P = 0.002). As for polymorphism in the interleukin 8 (-251) gene we observed that the AA (P = 0.026) and AT (P = 0.005) genotypes were most frequent in the group of patients with gastric adenocarcinoma. By comparing the different types of isolated bacterial strains with the interleukin -8 (-251) and the histopathological data we observed that carriers of the A allele (AT and AA) infected by virulent strains (m1s1 cagA+) demonstrated a greater risk of presenting a degree of inflammation (OR = 24.75 CI 95 percent 2.29-267.20 P = 0.004) and increased neutrophilic activity (OR = 28.71 CI 95 percent 2.62-314 P = 0.002) in the gastric mucosa. CONCLUSION: Our results demonstrate that the interaction between polymorphism in the interleukin -8 (-251) gene, particularly with carriers of the A allele and the infecting type of H. pylori strain (s1m1 cagA positive) performs an important function in development of gastric adenocarcinoma.

CONTEXTO: A neoplasia gástrica é a segunda causa mais comum de morte por câncer no mundo e o H. pylori é classificado como carcinógeno humano tipo I pela Organização Mundial de Saúde. Entretanto, apesar da elevada prevalência da infecção pelo H. pylori em todo mundo, menos de 3 por cento de indivíduos portadores dessa bactéria desenvolvem neoplasias gástricas. Tal fato indica que a evolução para malignização possa estar associada a fatores bacterianos, do hospedeiro e do ambiente. OBJETIVOS: Investigou-se a associação do polimorfismo da região promotora do gene IL-8 (-251) e do genótipo do H. pylori, baseado nos alelos vacA e na presença do gene cagA, com a clínica e os dados histopatológicos. MÉTODOS: Em estudo prospectivo, 102 pacientes com câncer gástrico e 103 voluntários saudáveis foram analisados. O polimorfismo da IL-8 (-251) foi determinado pela reação de PCR-RFLP e sequenciamento. Para genotipagem dos alelos vacA e do gene cagA das cepas bacterianas foi utilizada a PCR. As biopsias gástricas foram avaliadas histologicamente. RESULTADOS: A sorologia para o H. pylori foi positiva em 101 (99 por cento) de todos os pacientes analisados, e 98 (97 por cento) deles foram colonizados por apenas uma cepa bacteriana. Em pacientes com monoinfecção, 82 (84 por cento) das cepas bacterianas observadas apresentavam o genótipo s1b/m1. O gene cagA foi detectado em 74 (73 por cento) dos pacientes infectados pelo H. pylori. A presença do gene cagA demonstrou estar associada com a presença do genótipo s1b/m1 do gene vacA (P = 0,002). Quanto ao polimorfismo do gene da IL-8 (-251), observou-se que os genótipos AA (P = 0,026) e AT (P = 0,005) foram mais frequentes no grupo de pacientes com adenocarcinoma gástrico. Comparando os diferentes tipos de cepas bacterianas isoladas, com o polimorfismo do gene da IL-8-251 e dados histopatológicos, observou-se que, portadores do alelo A (AT e AA) infectados por cepas virulentas (m1s1 cagA+), demonstraram risco aumentado de apresentar maior grau de inflamação (OR = 24,75 IC 95 por cento 2,29-267,20 P = 0,004) e aumento da atividade neutrofílica (OR = 28,71 IC 95 por cento 2.62-314 P = 0,002) na mucosa gástrica. CONCLUSÃO: Os resultados demonstram que a interação entre o polimorfismo do gene da IL-8, particularmente em portadores do alelo A, e o tipo de cepa infectante do H. pylori (s1m1 cagA positiva) desempenha importante função no desenvolvimento do câncer gástrico.