Evaluation of the immunomodulatory effect of Bougainvillea xbuttiana (Var. Orange) on the cytokine production induced by Botrhops jararaca venom in macrophages / Evaluación del efecto inmunomodulador de Bougainvillea xbuttiana (var. naranja) sobre la producción de citoquinas de macrófagos inducida pelo veneno de Bothrops jararaca

To study the effect of 50% ethanol extract of Bougainvillea xbuttiana on the enzymatic activity, cell via bility and cytokine production provoked by the venom of Bothrops jararaca in macro - phages. Three assays were used to study the effects of B. xbuttiana extract on the damage pro - duced by B. jararaca : Enzymatic activity was detected by measuring the proteoly tic and phos - pholipase A2; macrophages cytotoxicity was determined by the MTT method; levels of cytokine were evaluated using ELISA and a biological assay. After treatment with 300 µg/mL B. xbuttiana extract for 30 min, the proteolytic and phospholipase A2 activities of the venom were reduced to 95 and 61%, respectively. In macrophages cultures treated with B. xbuttiana extract combined with venom, the production of TNF - α, IL - 6 and IFN - γ was reduced, whereas IL - 10 was potenti - ated. Our results support the potential effect of the B. xbuttiana extract as a complementary therapy against the toxicity caused by the venom of B . jararaca snakes

Estudiar el efecto del extracto etanólico al 50% de Bougainvillea xbuttiana sobre la actividad enzimática viabilidad celular y producci ón de citoquinas provocada por el veneno de Bothrops jararaca en macrófagos Se utilizaron tres ensayos para estudiar los efectos del extracto de B. xbuttiana sobre el daño producido por B. jararaca : Se detectó actividad enzimática mediante la medición del proteolítico y fosfolipasa A2; la citotoxicidad de los macrófagos se determinó por el método MTT; Los niveles de citoquinas se evaluaron utilizando ELISA y un ensayo biológico. Después del tratamiento con 300 µg/mL de extracto de B. xbuttiana durante 30 mi n, las actividades proteolíticas y de fosfolipasa A2 del veneno se redujeron a 95 y 61%, respectivamente. En cultivos de macrófagos tratados con extracto de B. xbuttiana combinado con veneno, la producción de TNF - α, IL - 6 e IFN - γ se redujeron, mientras que IL - 10 se potenció. Nuestros resultados apoyan el efecto potencial del extracto de B. xbuttiana como terapia complementaria frente a la toxicidad provocada por el veneno de B. jararaca .

Evaluation of serum placenta-specific gene 8 protein, total antioxidant capacity, interleukin-10, interleukin-17A, interleukin-21 and interleukin-33 levels in Turkish women with gestational diabetes mellitus.

PURPOSE: Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that begins or is diagnosed during pregnancy. Our study aimed to establish a correlation between proinflammatory and anti-inflammatory response in order to be able to develop treatment strategies and determine early diagnosis biomarkers in the sera of cases diagnosed with GDM. Moreover, we aimed to investigate interleukin (IL), placenta-specific gene 8 protein (PLAC8) and total antioxidant capacity (TAC) in patients with GDM. METHODS: A total of 121 patients were included in the study. These were divided into four patient groups: pregnant and diagnosed with DM (P-GDM, n=30); pregnant and not diagnosed with DM (P-NGDM, n=32); non-pregnant diagnosed with DM (NP-DM, n=29) and non-pregnant and not diagnosed with DM (NPNDM, n=30). IL-10, IL-17A, IL-21, IL-33, PLAC8 and TAC determinations from patients were evaluated by ELISA (Enzyme-Linked ImmunoSorbent Assay) method. RESULTS: IL-10 and IL-33 concentrations were found to be significantly higher in P-GDM and NP-DM patient groups compared to P-NGDM and NP-NDM groups (p<0.001). The PLAC8 level in the P-GDM patient group (20.38±5.37) was determined to be significantly higher than in the P-NGDM patient group (3.41±2.17, p<0.001). TAC in the P-NGDM and NP-NDM groups (12.42±2.31 vs. 12.96±3.78, p<0.001) was determined to be significantly higher than in the P-GDM and NP-DM groups (4.8±0.52 vs. 2.21±0.71, p<0.001). DISCUSSION: The fact that the importance of PLAC8 level and TAC in the diagnosis and follow-up of GDM in pregnancy is demonstrated for the first time in this study shows that it is unique.

INFLAMMATORY IMMUNOPATHOLOGY OF COVID-19 AND ITS CORRELATION WITH THE SEVERITY OF THE DISEASE / IMUNOPATOLOGIA INFLAMATÓRIA DA COVID-19 E SUA CORRELAÇÃO COM A GRAVIDADE DA DOENÇA

SARS-CoV-2, which caused the coronavirus pandemic in 2019 (COVID-19), is a beta-coronavirus, and its infection in host cells can activate innate and adaptive immune responses through the activation of several pro-inflammatory cytokines. Thus, in this study we established the relationship between the severity and immunopathology of COVID-19 through the main inflammatory cytokines. Results show that tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) and interleukins (IL), such as IL-6, are stimulated by the activation of T cell subsets, which results in immune-mediated cellular destruction. Several cytokines reduce the immune response and predispose to a pro-inflammatory and auto-reactive state, including IL-1ß, IL-1RA, IL-7, IL-8, IL-9, IL-10, and associated inflammatory markers (LDH, GM-CSF and VEGF). These higher cytokine levels end up favoring tissue damage in multiple systems, including lungs, heart, gastrointestinal, brain, kidneys and other organs. Increasingly, a greater impact of the markers IL-6, ferritin, pro-calcitonin, lactic dehydrogenase, D-dimer and hypoalbuminemia was observed in patients with severe infection of the disease. In general, the data analyzed confirmed that COVID-19 severity is not caused simply by the viral infection, but rather by immune response and aberrant inflammation. In this way, this study allows a contribution to clinical practice, and it shows that it is essential to carry out in-depth studies about the immunopathology of COVID-19, in order to determine the severity markers involved in the pathogenesis of the viral infection.

O SARS-CoV-2, causador da doença coronavírus 2019 (COVID-19), é um beta-coronavírus, e sua infecção nas células do hospedeiro pode ativar respostas imunes inata e adaptativa, por meio da secreção de várias citocinas pró-inflamatórias. Assim, estabelecemos neste estudo a correlação da gravidade e imunopatologia da COVID-19 com as principais citocinas inflamatórias. Resultados mostram que o fator de necrose tumoral alfa (TNF-α), interferon-gama (IFN-γ) e interleucinas (IL), como a IL-6, são estimulados pela ativação de subconjuntos de células T, o que resulta em destruição celular imunomediada. Sendo que, diversas citocinas deprimem a resposta imune sadia, e predispõem a um estado pró-inflamatório e auto-reativo, dentre elas, IL-1ß, IL-1RA, IL-7, IL-8, IL-9, IL-10, e os marcadores inflamatórios associados (LDH, GM-CSF e VEGF). Isso acaba por favorecer danos teciduais em múltiplos sistemas, como no pulmonar, cardíaco, gastrointestinal, cerebral, renal, dentre outros. Acrescenta-se que foi observado um impacto maior dos marcadores IL-6, ferritina, pró-calcitonina, desidrogenase láctica, D-dímero e hipoalbuminemia em pacientes com infecção grave da doença. De forma geral, pela análise de dados, verificou-se que a gravidade da doença COVID-19 parece ser modulada não apenas pela infecção viral, mas também por respostas imunes e inflamatórias aberrantes no hospedeiro. Dessa forma, este estudo permite contribuir para o auxílio da prática clínica, sendo imprescindível a realização de estudos aprofundados acerca da imunopatologia da COVID-19, a fim de que se determine os marcadores de gravidade envolvidos na patogênese da infecção viral.

Evaluación del efecto inmunomodulador de Bougainvillea xbuttiana (var. naranja) sobre la producción de citoquinas de macrófagos inducida pelo veneno de Bothrops jararaca

To study the effect of 50% ethanol extract of Bougainvillea xbuttianaon the enzymatic activity, cell viability and cytokine production provoked by the venom of Bothrops jararacain macro-phages. Three assays were used to study the effects of B. xbuttianaextract on the damage pro-duced by B. jararaca: Enzymatic activity was detected by measuring the proteolytic and phos-pholipase A2; macrophages cytotoxicity was determined by the MTT method; levels of cytokine were evaluated using ELISA and a biological assay. After treatment with 300 μg/mL B. xbuttianaextract for 30 min, the proteolytic and phospholipase A2activities of the venom were reduced to 95 and 61%, respectively. In macrophages cultures treated with B. xbuttianaextract combined with venom, the production of TNF-α, IL-6 and IFN-γ was reduced, whereas IL-10 was potenti-ated. Our results support the potential effect of the B. xbuttianaextract as a complementary therapy against the toxicity caused by the venom of B. jararacasnakes.

Use of probiotics and similar in pediatric patients with Type 1 Diabetes Mellitus: a systematic review / Uso de probióticos e similares em pacientes pediátricos com Diabetes Mellitus tipo 1: uma revisão sistemática

ABSTRACT Objective: To perform a systematic review of randomized controlled trials, evaluating the effect of probiotics, prebiotics or symbiotics supplementation on glycemic and inflammatory control in children with Type 1 Diabetes Mellitus (T1DM). Data source: The Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Clinical Trials, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Electronic Library Online (SciELO) databases were searched. Randomized clinical trials of pediatric patients with DM1 using probiotics, prebiotics or symbiotics were included, regardless of year or language of publication. Studies that did not evaluate glycated hemoglobin (HbA1c) were excluded. Metabolic results (HbA1c, total insulin dose and C-peptide) and inflammatory control [interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)] during probiotic supplementation or similar, related to modification of the intestinal microbiota, were analyzed. PROSPERO ID: CRD42022384485. Data synthesis: Five studies were selected for a systematic review. Regarding metabolic markers, only one of the articles that analyzed HbA1c showed a significant decrease (p=0.03) in the intervention group. One study identified a reduction in the total dose of insulin and increased C-peptide levels. Regarding the evaluation of inflammatory parameters (IL-10, TNF-α, INF-γ), there were no statistical relevant modifications. Conclusions: Current data from the literature were not conclusive in identifying an improvement in glycemic control and did not observe changes in inflammatory parameters with the use of probiotics, prebiotics or symbiotics in pediatric patients with T1DM.

RESUMO Objetivo: Realizar uma revisão sistemática de ensaios clínicos randomizados controlados avaliando o efeito da suplementação de probióticos, prebióticos ou simbióticos no controle glicêmico e inflamatório em crianças com diabetes mellitus tipo 1 (DM1). Fontes de dados: As bases Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Clinical Trials, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Scientific Electronic Library Online (SciELO) foram pesquisadas. Foram incluídos ensaios clínicos randomizados de pacientes pediátricos com DM1 em uso de probióticos, prebióticos ou simbióticos, independentemente de ano ou idioma de publicação. Foram excluídos os trabalhos que não avaliaram hemoglobina glicada (HbA1c). Os resultados metabólicos (HbA1c, dose de insulina total e peptídeo C) e o controle inflamatório [interleucina-10 — IL-10), fator de necrose tumoral-alfa (TNF-α) e interferon-gama (IFN-γ)] durante a suplementação de probióticos ou similares, relacionados à modificação da microbiota intestinal, foram analisados. ID PROSPERO: CRD42022384485. Síntese dos dados: Cinco estudos foram selecionados para revisão sistemática. Com relação aos marcadores metabólicos, apenas um dos artigos que analisaram a HbA1c apresentou diminuição significativa (p=0,03) no grupo intervenção. Um estudo identificou redução da dose total de insulina e aumento dos níveis de peptídeo C. Quanto à avaliação dos parâmetros inflamatórios (IL-10, TNF-α, INF-γ), não houve modificações de relevância estatística. Conclusões: Os dados atuais da literatura não foram conclusivos em identificar melhora no controle glicêmico e não observaram mudanças nos parâmetros inflamatórios com o uso de probióticos, prebióticos ou simbióticos em pacientes pediátricos com DM1.

Hidrogel associado a biovidro funcionalizado com ranelato de estrôncio: análise do sobrenadante in vitro / Hydrogel associated with bioglass functionalized with strontium ranelate: in vitro supernatant analysis

A utilização de sistemas de liberação de fármacos para evitar complicações sistêmicas foi o enfoque do trabalho apresentado. O fármaco utilizado foi o ranelato de estrôncio (SrR), medicamento indicado para osteoporose que auxilia na prevenção de fraturas ósseas. Incorporou-se ao sistema biomateriais que estimulam a formação de tecido ósseo, como o hidrogel e o biovidro. O hidrogel é um material polimérico que possui alta capacidade de retenção de água e pode ser injetado no local da lesão, preenchendo o defeito ósseo. O biovidro é um material cerâmico que possui propriedades osteocondutoras e osteoindutoras, ou seja, favorece a adesão e a diferenciação de células ósseas. O biovidro foi funcionalizado com o fármaco por meio da rota sonoquímica e incorporado aos hidrogéis produzidos. O objetivo deste trabalho foi avaliar a presença de citocinas, pró e anti-inflamatórias que participam da remodelação óssea, utilizando hidrogéis incorporados com partículas de biovidro funcionalizadas com medicamento sobre células mesenquimais in vitro. Foram preparados três tipos de materiais: hidrogel puro (HP), hidrogel com biovidro (HB) e hidrogel com biovidro funcionalizado com ranelato de estrôncio (HBR). Os materiais foram caracterizados por técnicas físico-químicas e biológicas, ensaio de viabilidade celular, ensaio de intumescimento e degradação. Foram realizados testes de cultura celular, utilizando células mesenquimais diferenciadas em osteoblastos, isoladas de fêmures de ratas ovariectomizadas. Os dados quantitativos foram submetidos ao teste de normalidade para a seleção do teste estatístico apropriado, com nível de significância de 5%. Os resultados mostraram que os materiais apresentaram boa interação entre os componentes, formando uma rede tridimensional porosa e homogênea. O ensaio de intumescimento e degradação mostrou a compatibilidade do hidrogel proposto para sistemas de ação local, curva de crescimento compatível com tempo de resposta celular. No teste ELISA evidenciou-se a presença das citocinas IL1ß, IL-6, IL-10 e IL-17, sua expressão nas células mesenquimais analisadas e sua possível influência na remodelação óssea (AU)

The use of drug delivery systems to avoid systemic complications was the focus of the work presented. The drug used was strontium ranelate (SrR), a medication indicated for osteoporosis that helps prevent bone fractures. Biomaterials that stimulate the formation of bone tissue, such as hydrogel and bioglass, were incorporated into the system. The hydrogel is a polymeric material that has a high-water retention capacity and can be injected into the injury site, filling the bone defect. Bioglass is a ceramic material that has osteoconductive and osteoinductive properties, that is, it favors the adhesion and differentiation of bone cells. The bioglass was functionalized with the drug through the sonochemical route and incorporated into the hydrogels produced. The objective of this work was to evaluate the presence of pro- and anti-inflammatory cytokines that participate in bone remodeling, using hydrogels incorporated with bioglass particles functionalized with medication on mesenchymal cells in vitro. Three types of materials were prepared: pure hydrogel (HP), hydrogel with bioglass (HB) and hydrogel with bioglass functionalized with strontium ranelate (HBR). The materials were characterized by physicochemical and biological techniques, cell viability testing, swelling and degradation testing. Cell culture tests were carried out using mesenchymal cells differentiated into osteoblasts, isolated from the femurs of ovariectomized rats. Quantitative data were subjected to the normality test to select the appropriate statistical test, with a significance level of 5%. The results showed that the materials showed good interaction between the components, forming a porous and homogeneous three-dimensional network. The swelling and degradation test showed the compatibility of the proposed hydrogel for local action systems, a growth curve compatible with cellular response time. The ELISA test revealed the presence of the cytokines IL-1ß, IL-6, IL-10 and IL-17, their lower expression in cells from ovariectomized animals and their possible influence on bone remodeling. (AU)

Strength and endurance training in cytokine and body composition of people with hiv/aids / Entrenamiento de fuerza y resistencia en citoquinas y composición corporal de personas con vih/sida / Treinamento de força e resistência em citocinas e composição corporal de pessoas com hiv/aids

ABSTRACT Introduction: HIV/AIDS is considered one of the great cases of public health, but it is seen that patients who use antiretroviral therapy (ART) and practice strength training promote a promotion of their health. Objectives: Assess the impact of strength and resistance training on cytokines and body composition in people living with HIV/AIDS. Methods: Randomized clinical trial, the sample consisted of 12 patients, 7 from the Strength Group (GF) and 5 from Group 2, Muscular Resistance (MGR). We compared the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α cytokines and body composition in the first and last sessions. The patients completed 36 strength and resistance training sessions over 12 weeks. Results: After 36 sessions of GRM resistance training, there was a significant increase from 4,734 pg/mL to 5,050 pg/mL of IL-10 (p=0.002). Regarding the GFR, no significant results were found. For body composition, there were significant differences in GFR due to the increase in lean mass of the arms from 6,441g to 7,014g (p=0.04), legs from 16,379g to 17,281g (p=0.02) and whole body of 45,640g to 47,343g (p=0.01). In G2 there was a significant decrease in the percentage of fat in the arms from 23,160% to 20,750% (p = 0.04). To assess quality of life, the WHOQOL-HIV-Bref questionnaire was used, where significant improvement was found in all domains, except for the level of independence domain. Conclusion: We conclude that muscular resistance training is effective in increasing IL-10 and decreasing the percentage of fat in the arms, whereas strength training increases lean mass in arms, legs, and the whole body. Level of Evidence I; Randomized Clinical Trial.

RESUMEN Introducción: El VIH/SIDA es considerado uno de los grandes casos de salud pública, sin embargo, está comprobado que pacientes que hacen uso de la terapia antirretroviral (TARV) y practican entrenamiento de fuerza provoca una promoción de su salud. Objetivos: Evaluar el impacto del entrenamiento de fuerza en la resistencia a las citoquinas y en la composición corporal de las personas que viven con VIH/SIDA. Métodos: Ensayo clínico aleatorizado, la muestra estuvo compuesta por 12 pacientes, siete del Grupo de Fuerza (TFG) y cinco del Grupo de Resistencia Muscular (GRM). Se compararon los niveles de las citocinas IL-2, IL-4, IL-6, IL-10 y TNF-α y la composición corporal en la primera y la última sesión. Los pacientes completaron 36 sesiones de entrenamiento de fuerza y resistencia durante 12 semanas. Resultados: Tras 36 sesiones de entrenamiento de resistencia GRM, se produjo un aumento significativo de 4.734 pg/mL a 5.050 pg/mL de IL-10 (p=0,002). En cuanto a la TFG, no se encontraron resultados significativos. En cuanto a la composición corporal, hubo diferencias significativas en la TFG debido al aumento de la masa magra en brazos de 6.441g a 7.014g (p=0,04), piernas de 16.379g a 17.281g (p=0,02) y cuerpo entero de 45.640g a 47.343g (p=0,01). En el GRM hubo una disminución significativa del porcentaje de grasa en los brazos de 23.160% a 20.750% (p = 0,04). Para la evaluación de la calidad de vida se utilizó el cuestionario WHOQOL-HIV-Bref, donde se encontró una mejoría significativa en todos los dominios, excepto en el dominio nivel de independencia. Conclusión: Concluimos que el entrenamiento de resistencia muscular es eficaz para aumentar la IL-10 y disminuir el porcentaje de grasa en los brazos, mientras que el entrenamiento de fuerza aumenta la masa magra total. Nivel de Evidencia I; Ensayo clínico aleatorizado.

RESUMO Introdução: O HIV/AIDS é considerado um dos grandes casos de saúde pública, porém verifica-se que pacientes que fazem uso de terapia antirretroviral (TARV) e praticam treinamento de força provocam uma promoção de sua saúde. Objetivos: Avaliar o impacto do treinamento de força sobre a resistência nas citocinas e a composição corporal de pessoas vivendo com HIV/AIDS. Métodos: Ensaio clínico randomizado, a amostra foi composta por 12 pacientes, sendo sete do Grupo Força (TFG) e cinco do Grupo Resistência Muscular (GRM). Comparou-se os níveis das citocinas IL-2, IL-4, IL-6, IL-10 e TNF-α e a composição corporal na primeira e na última sessão. Os pacientes completaram 36 sessões de treinamento de força e resistência ao longo de 12 semanas. Resultados: Após 36 sessões de treinamento resistido GRM, houve um aumento significativo de 4.734 pg/mL para 5.050 pg/mL de IL-10 (p=0,002). Em relação à TFG, não foram encontrados resultados significativos. Para composição corporal, houve diferenças significativas na TFG devido ao aumento da massa magra dos braços de 6.441g para 7.014g (p=0,04), pernas de 16.379g para 17.281g (p=0,02) e corpo inteiro de 45.640g para 47.343g (p=0,01). No GRM houve diminuição significativa do percentual de gordura nos braços de 23.160% para 20.750% (p = 0,04). Para avaliação da qualidade de vida foi utilizado o questionário WHOQOL-HIV-Bref, onde foi encontrada uma melhora significativa em todos os domínios, exceto no domínio nível de independência. Conclusão: Conclui-se que o treinamento de resistência muscular é eficaz em aumentar a IL-10 e diminuir o percentual de gordura nos braços, enquanto o treinamento de força aumenta a massa magra geral. Nível de Evidência I; Ensaio Clínico Randomizado.

Systemic Inflammatory Patterns in Ovarian Cancer Patients: Analysis of Cytokines, Chemokines, and Microparticles / Padrões inflamatórios sistêmicos em pacientes com câncer de ovário: Análise de citocinas, quimiocinas e micropartículas

Abstract Objective To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. Materials and Methods We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Results Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. Conclusion The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.

Resumo Objetivo Comparar os padrões de resposta inflamatória sistêmica em mulheres com câncer epitelial de ovário (CEO) ou sem evidência de doença maligna, bem como avaliar o perfil de respostas inflamatórias sistêmicas em tumores dos tipos 1 e 2. Esta é uma forma não invasiva e indireta de avaliar tanto a atividade tumoral quanto o papel do padrão inflamatório durante as respostas pró- e antitumorais. Métodos Ao todo, 56 pacientes foram avaliados prospectivamente: 30 mulheres sem evidência de doença maligna e 26 mulheres com CEO. A quantificação plasmática de citocinas, quimiocinas e micropartículas (MPs) foi realizada por citometria de fluxo. Resultados Os níveis plasmáticos das citocinas pró-inflamatórias interleucina-12 (IL12), interleucina-6 (IL-6), fator de necrose tumoral alfa (tumor necrosis factor alpha, TNF-α, em inglês), interleucina-1 beta (IL-1β), e interleucina-10 (IL-10), e da quimiocina de motivo C-X-C 9 (CXCL-9) e da quimiocina de motivo C-X-C 10 (CXCL-10) foram significativamente maiores em pacientes com EOC do que nos controles. Os níveis plasmáticos da citocina interleucina-17A (IL17A) e MPs derivados de células endoteliais foram menores em pacientes com CEO do que no grupo de controle. A frequência de leucócitos e de MPs derivadas de células endoteliais foi maior nos tumores de tipo 2 do que naqueles sem malignidade. Observou-se um número expressivo de citocinas e quimiocinas inflamatórias/regulatórias nos casos de CEO, além de correlações negativas e positivas entre elas, o que leva a uma maior complexidade dessas redes. Conclusão Este estudo mostrou que, por meio da construção de redes compostas por citocinas, quimiocinas e MPs, há maior resposta inflamatória sistêmica em pacientes com CEO e correlação mais complexa desses biomarcadores em tumores de tipo 2.

[Síndrome hemofagocítico linfohistiocitario secundario a Dengue en una paciente de 6 años: reporte de caso].

Background: Dengue fever is a mosquito-borne infectious disease endemic in over 100 countries around the world. Among the complications that dengue can cause the Hemophagocytic Lymphohistiocytosis is one of great concern for its severity and complex diagnosis. Case report: Hereby we document a case of this disease expressed on a previously healthy 6-year-old female patient whose dengue infection was so severe that needed intensive care management with vasoactive drugs and diuretics. After a short period of wellness began newly with fever, pancytopenia, hepatitis, and inflammatory response symptoms. Conclusions: A Dengue associated Hemophagocytic Lymphohistiocytosis syndrome was suspected and treated with intravenous corticosteroids on a 3-day scheme at no signs of malignancy with excellent response. The health care professionals must know about this not novel entity in order to reach an efficient diagnosis and treatment mostly, but not only, those in tropical and sub-tropical regions of the word were dengue virus is endemic.

Antecedentes: La fiebre por dengue es una enfermedad infecciosa transmitida por mosquitos, endémica en más de 100 países alrededor del mundo. La Linfohistiocitosis Hemofagocítica, dentro de las complicaciones que puede ocasionar el dengue, es una de las más preocupantes por su complejidad diagnostica y gravedad. Reporte de caso: Femenino de 6 años de edad, previamente sana, cuya infección por dengue fue tan grave que requirió manejo en cuidados intensivos. Después de un breve período de bienestar recrudeció la fiebre, además de pancitopenia, hepatitis y síntomas de respuesta inflamatoria. Conclusiones: Se sospechó síndrome de Linfohistiocitosis Hemofagocítica asociada a Dengue y se trató con corticoides intravenosos en un esquema de 3 días con excelente respuesta. Los profesionales de la salud deben conocer esta entidad no novedosa para poder llegar a un diagnóstico y tratamiento eficaz en su mayoría, pero no solo, en las regiones tropicales y subtropicales del mundo donde el virus del dengue es endémico.

Increased circulating interleukin-23 level in patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a Th1-mediated chronic inflammatory disease characterized by non-caseating granulomas. Its pathogenesis is not yet clear, but the possible role of various proinflammatory cytokines is being discussed. AIM: This study aims to determine serum cytokine (IL-6, IL-12, IL-17, and IL-23) levels in patients with sarcoidosis, and to determine a possible correlation with clinical and laboratory findings of the disease. MATERIAL AND METHOD: Forty-four biopsy-proven sarcoidosis patients followed up at a single centre and 41 healthy volunteers were included in the study. Demographic, clinical, laboratory, and radiological data of all patients were recorded. Serum samples from the patients and the control group were taken and IL-6, IL-12, IL-17, IL-23 were measured by ELISA method. RESULTS: Of the 44 sarcoidosis patients, 13(29.5%) were male and 31(70.5%) were female. Average patient age was 47.4 years, mean disease duration was 3.2 years. Twenty-one (47.7%) patients had erythema nodosum, three (6.8%) had uveitis, 40(90.9%) had arthralgia, 23(52.3%) had ankle arthritis, 15(34.1%) had enthesitis. Laboratory evaluation showed increased serum ACE levels in 24(54.5%) patients, increased serum calcium levels in 11 (25%) patients, increased serum D3 levels in 5(11.4%) patients, increased ESR and CRP levels in 22(50%) and 23(52.3%) patients, respectively. Compared with the control group higher serum IL-23 levels were found in the patients with sarcoidosis (p=.01). Serum IL-23 was associated with ankle arthritis (p=.02). Serum IL-6, IL-12, and IL-17 levels were similar in the sarcoidosis patients and the control group (p=.128, p=.212, p=.521 respectively). CONCLUSION: In our study, we found increased serum IL-23 in patients with sarcoidosis, while serum IL-6, IL-12, and IL-17 were detected as normal. Although our results are somewhat contradictory to other studies in the literature, the question should still be whether sarcoidosis is a Th1/Th17 disease. Multicentre studies are needed in this regard.

Correlation between inflammatory mediators and biochemical markers in patients with active pulmonary tuberculosis / Correlação entre mediadores inflamatórios e marcadores bioquímicos em pacientes com tuberculose pulmonar ativa

Objective: Correlate inflammatory mediators and biochemical parameters in patients with active pulmonary tuberculosis (TB) treated at a public hospital in São Luís, MA. Methods: This is a case-control study of patients with a positive diagnosis of active pulmonary TB. Serum samples from patients and the control group were collected for the clinical trials, and epidemiological data were collected through medical records and interviews. The control group consisted of healthy volunteers with no previous contact with TB cases, matched by age and sex to the clinical group. To measure inflammatory cytokines, we used the Human IL-6 ELISA Set and Human IFN-γ ELISA Set kits. Oxidative stress was measured by quantification of thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO). In biochemistry, the levels of uric acid, antistreptolysin "O" (AEO), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), calcium, total cholesterol, gamma-glutamyl transferase (Gamma GT), glucose, alkaline phosphatase, high-density lipoprotein (HDL), C-reactive protein (CRP) and triglycerides were measured. Results: The clinical group consisted of 53 patients. There was a substantial decrease in IFN-γ (p<0.0001) and a significant increase in IL-6 (p<0.0001). TBARS production increased significantly (p= 0.0414). There was no significant difference in NO production (p= 0.3194). In biochemistry, there was a significant increase in ALT (p= 0.0072), AST (p= 0.0016), Gamma GT (p= 0.0011), alkaline phosphatase (p<0.0001), CRP (p<0. .0001) and triglycerides (p= 0.0343), and a significant decrease in calcium (p<0.0001). A significant positive correlation was found between IL-6 and IFN-γ (p= 0.0448), as well as AST and ALT (p<0.0001); CRP and gamma GT (p<0.0001); Gamma GT and ALT (p= 0.0016); Gamma GT and AST (p=0.0004); triglycerides and cholesterol (p= 0.0002); alkaline phosphatase and gamma GT (p<0.0001); CRP and alkaline phosphatase (p<0.0001); triglycerides and calcium (p= 0.0121); cholesterol and calcium (p= 0.0261); glucose and cholesterol (p= 0.0373); and triglycerides and glucose (p= 0.0127) in biochemistry, with a significant negative correlation between glucose and uric acid (p= 0.0092); and CRP and HDL (p=0.0037). The correlation between inflammatory mediators and biochemical markers was positive between IL-6 and gamma GT (p= 0.0011); IL-6 and CRP (p<0.0001); IL-6 and alkaline phosphatase (p=0.0076); and NO and triglycerides (p= 0.0016), and significant negative correlation between IFN-γ and cholesterol (p= 0.0171) and TBARS and cholesterol (p= 0.0138). Conclusion: Immunosuppression of IFN-γ activity was observed. A correlation was found between IL-6 and inflammatory biochemical markers, indicating damage and injury caused by M. tuberculosis (AU).

Objetivo: Correlacionar mediadores inflamatórios e parâmetros bioquímicos em pacientes com tuberculose (TB) pulmonar ativa atendidos em um hospital público, em São Luís, MA. Métodos: Trata-se um caso-controle de pacientes com diagnóstico positivo para TB pulmonar ativa. Amostras de soro dos pacientes e grupo controle foram coletadas para os experimentos clínicos e os dados epidemiológicos foram coletados por meio de prontuários e entrevistas. O grupo controle foi formado por voluntários saudáveis sem contato prévio com casos de TB, pareados com idade e sexo ao grupo clínico. Para dosar citocinas inflamatórias, utilizaram-se os kits Human IL-6 ELISA Set e Human IFN-γ ELISA Set. Mediu-se o estresse oxidativo pela quantificação das espécies reativas do ácido tiobarbitúrico (TBARS) e óxido nítrico (ON). Na bioquímica, mediram-se os níveis de ácido úrico, anti-estreptolisina-O (AEO), alanina aminotransferase (ALT), amilase, aspartato aminotransferase (AST), cálcio, colesterol total, gama glutamil transferase (Gama GT), glicose, fosfatase alcalina, lipoproteína de alta densidade (HDL), proteína C reativa (PCR) e triglicerídeos. A análise estatística foi realizada pelo software Graph Pad Prism 8, com p<0,05 significativo. Re -sultados: O grupo clínico foi formado por 53 pacientes. Houve uma diminuição significativa de IFN-γ (p<0,0001), e aumento significativo de IL-6 (p<0,0001). A produção de TBARS aumentou significativamente (p= 0,0414). Não houve diferença significativa na produção de ON (p= 0,3194). Na bioquímica, houve aumento significativo em ALT (p= 0,0072), AST (p= 0,0016), gama GT (p= 0,0011), fosfatase alcalina (p<0,0001), PCR (p<0,0001) e triglice-rídeos (p= 0,0343), e diminuição significativa de cálcio (p<0,0001). Encontrou-se correlação positiva significativa entre IL-6 e IFN-γ (p= 0,0448), assim como AST e ALT (p<0,0001); PCR e gama GT (p<0,0001); gama GT e ALT (p= 0,0016); gama GT e AST (p= 0,0004); triglicerídeos e colesterol (p= 0,0002); fosfatase alcalina e gama GT (p<0,0001); PCR e fosfatase alcalina (p<0,0001); triglicerídeos e cálcio (p= 0,0121); colesterol e cálcio (p= 0,0261); glicose e colesterol (p= 0,0373); e triglicerídeos e glicose (p= 0,0127) na bioquímica, sendo negativa significativa entre glicose e ácido úrico (p= 0,0092); e PCR e HDL (p= 0,0037). A correlação entre marcadores infla-matório e bioquímicos foi positiva entre IL-6 e gama GT (p= 0,0011); IL-6 e PCR (p<0,0001); IL-6 e fosfatase alcalina (p= 0,0076); e ON e triglicerídeos (p= 0,0016), e negativa significativa entre IFN-γ e colesterol (p= 0,0171) e TBARS e colesterol (p= 0,0138). Conclusões: Observou-se imunossupressão da atividade de IFN-γ. Encontrou-se correlação entre IL-6 e marcadores bioquímicos inflamatórios, indicando dano e lesão causados por M. tuberculosis (AU).

Increased circulating interleukin-23 level in patients with sarcoidosis / Incremento del nivel circulante de interleucina 23 en los pacientes con sarcoidosis

Background: Sarcoidosis is a Th1-mediated chronic inflammatory disease characterized by non-caseating granulomas. Its pathogenesis is not yet clear, but the possible role of various proinflammatory cytokines is being discussed. Aim: This study aims to determine serum cytokine (IL-6, IL-12, IL-17, and IL-23) levels in patients with sarcoidosis, and to determine a possible correlation with clinical and laboratory findings of the disease. Material and method: Forty-four biopsy-proven sarcoidosis patients followed up at a single centre and 41 healthy volunteers were included in the study. Demographic, clinical, laboratory, and radiological data of all patients were recorded. Serum samples from the patients and the control group were taken and IL-6, IL-12, IL-17, IL-23 were measured by ELISA method. Results: Of the 44 sarcoidosis patients, 13(29.5%) were male and 31(70.5%) were female. Average patient age was 47.4 years, mean disease duration was 3.2 years. Twenty-one (47.7%) patients had erythema nodosum, three (6.8%) had uveitis, 40(90.9%) had arthralgia, 23(52.3%) had ankle arthritis, 15(34.1%) had enthesitis. Laboratory evaluation showed increased serum ACE levels in 24(54.5%) patients, increased serum calcium levels in 11 (25%) patients, increased serum D3 levels in 5(11.4%) patients, increased ESR and CRP levels in 22(50%) and 23(52.3%) patients, respectively. Compared with the control group higher serum IL-23 levels were found in the patients with sarcoidosis (p=.01). Serum IL-23 was associated with ankle arthritis (p=.02). Serum IL-6, IL-12, and IL-17 levels were similar in the sarcoidosis patients and the control group (p=.128, p=.212, p=.521 respectively). Conclusion: In our study, we found increased serum IL-23 in patients with sarcoidosis, while serum IL-6, IL-12, and IL-17 were detected as normal.(AU)

Antecedentes: La sarcoidosis es una enfermedad inflamatoria crónica mediada por Th1, caracterizada por granulomas no caseificantes. Su patogenia no está clara todavía, aunque se está debatiendo el posible rol de las diversas citocinas proinflamatorias. Objetivo: El objetivo de este estudio es determinar los niveles de citocinas séricas (IL-6, IL-12, IL-17 e IL-23) en los pacientes con sarcoidosis, así como establecer una posible correlación con los hallazgos clínicos y de laboratorio de la enfermedad. Material y método: Se incluyó en el estudio a 44 pacientes con sarcoidosis verificada mediante biopsia, cuyo seguimiento se realizó en un único centro, y 41 voluntarios sanos. Se registraron los datos demográficos, clínicos, de laboratorio y radiológicos de todos los pacientes. Se tomaron muestras séricas de los pacientes y el grupo control, midiéndose los niveles de IL-6, IL-12, IL-17 e IL-23 mediante el método ELISA. Resultados: De los 44 pacientes con sarcoidosis, 13 (29,5%) fueron varones y 31 (70,5%) fueron mujeres. La edad media de los pacientes fue de 47,4 años, y la duración media de la enfermedad fue de 3,2 años. Veintiún (47,7%) pacientes tenían eritema nudoso, 3 (6,8%) tenían uveítis, 40 (90,9%) tenían artralgia, 23 (52,3%) tenían artritis de tobillo y 15 (34,1%) tenían entesitis. La evaluación de las pruebas de laboratorio reflejó un incremento de los niveles séricos de ECA en 24 (54,5%) pacientes, de los niveles séricos de calcio en 11 (25%) pacientes, de los niveles séricos de D3 en 5 (11,4%) pacientes y de los niveles de ESR y PCR en 22 (50%) y 23 (52,3%) pacientes, respectivamente. En comparación con el grupo control, se encontraron niveles séricos de IL-23 más elevados en los pacientes con sarcoidosis (p=0,01). Los niveles séricos de IL-23 estuvieron asociados a artritis de tobillo (p=0,02)...(AU)

Regulación de la respuesta inflamatoria dependiente de citocinas / Regulation of the inflammatory response dependent on cytokines i: en

Las citocinas son hormonas proteicas que permiten la comunicación intercelular, estimulan la activación de receptores de membrana específicos, poseen funciones de diferenciación celular y proliferación, participan en la quimiotaxis, así como en el crecimiento y la modulación de la secreción de inmunoglobulinas; no obstante, su acción principal está dada por la regulación del mecanismo de la inflamación. Las principales citocinas encargadas de esto son las interleucinas 1, 8, 12 y 16; además del factor de necrosis tumoral alfa e interferones, todas ellas proinflamatorias. Las interleucinas 6 y 12 también actúan en la inmunidad específica.

Cytokines are protein hormones that allow the intercellular communication, stimulate the activation of specific membrane receptors, have cell differentiation functions and proliferation, participate in the chemotaxis, as well as in the growth and modulation of immunoglobulin secretion; nevertheless, their main action is given by the regulation of the inflammation mechanism. The main cytokines in charge of this are interleukins 1, 8, 12 and 16, besides the tumor necrosis factor alpha and interferons, all of them proinflammatory. Interleukins 6 and 12 also act in the specific immunity.

Association between interleukin-6 and lower urinary tract symptoms of benign prostatic hyperplasia / Relación entre la interleucina-6 y los síntomas urinarios de la hiperplasia prostática benigna

Objective: To evaluate the association between IL-6 in prostatic tissue/blood sample and BPH-LUTS, so as to preliminarily discover an indicator of inflammation that could show the severity of LUTS. Patients and methods: The prostatic tissues and blood samples were collected from 56 patients who underwent transurethral plasmakinetic resection of the prostate (TUPKRP). The association between IL-6 detected on prostatic tissues/blood sample and LUTS parameters, including international prostate symptom score (IPSS), peak flow rate (Qmax) and urodynamic parameters were analyzed with SPSS version 18.0, and p-value <0.05 was chosen as the criterion for statistical significance. Results: The TPSA and prostate volume (PV) were found to be higher in the inflammation group (p=0.021, 0.036). There was a positive association between prostate tissue inflammation and LUTS ([IPSS, storage symptoms score (SSS), voiding symptoms score (VSS), p<0.05], [Qmax, p=0.025], [obstruction, p=0.027] and [AUR, p=0.018]). The level of serum IL-6 was significantly higher in inflammatory group (p=0.008). However, no differences were observed in different degrees of inflammation (p=0.393). The level of IL-6 in prostatic tissue significantly increased with the degree of inflammation (p<0.001), and the intensity of IL-6 expression was statistically correlative with the degree of inflammation (p<0.001). The IL-6 expression in prostatic tissue was statistically relevant with IPSS (p=0.018) and SSS (p=0.012). Conclusion: IL-6 expression in prostatic tissue is associated with storage IPSS, suggesting chronic inflammation might contribute to storage LUTS. (AU)

Objetivo: Evaluar la relación entre il-6 y bph-lut en muestras de tejido prostático/sangre, con el fin de identificar indicadores de inflamación que reflejen la gravedad de los lut. Pacientes y métodos: Se recolectaron muestras de tejido prostático y sangre de 56 pacientes sometidos a una plasmatectomía transuretral prostática. Se aplicó la versión 18.0 de SPSS para analizar la correlación entre el il-6 de tejido prostático/muestra de sangre y los parámetros relacionados con los LUTS (puntuación internacional de síntomas prostáticos (IPSS), flujo máximo (Qmax), parámetros urodinámicos), con UN valor p<0,05 como criterio para una diferencia estadísticamente significativa. Resultados: Hubo diferencias estadísticamente significativas (p=0,021, 0,036) entre el grupo con inflamación y el grupo sin inflamación en TPSA y PV. La inflamación del tejido prostático se relacionó positivamente con LUTS ([IPSS, puntuación de síntomas de almacenamiento (SSS), puntuación de síntomas de micción (VSS), p<0,001), y la intensidad de la expresión de il-6 se correlacionó estadísticamente con el grado de inflamación (p<0,001). La expresión de il-6 en el tejido prostático fue estadísticamente significativa con IPSS (p=0,018) y SSS (p=0,012). Conclusiones: La expresión de il-6 en el tejido prostático está relacionada con el almacenamiento de IPSS, lo que sugiere que la inflamación crónica puede estar involucrada en el almacenamiento de LUTS. (AU)

Anti-Ro52/TRIM21 antibodies are associated with aberrant inflammatory circuits in patients with systemic autoimmune rheumatic diseases.

INTRODUCTION: Anti-Ro52/TRIM21 antibodies are markers for several systemic autoimmune rheumatic diseases (SARD). OBJECTIVE: To assess whether anti-Ro52/TRIM21 antibodies are related to abnormalities in inflammatory circuits. METHODS: Cross-sectional study of consecutive outpatients with SARD. Anti-Ro52/TRIM21 antibodies and serum amyloid A protein were measured by ELISA; panels for 18 cytokines and nine chemokines were analyzed on a Luminex reading platform, while high-sensitivity C-reactive protein (hs-CRP) and complement were measured by nephelometry. RESULTS: Among 167 included patients, 143 had systemic lupus erythematosus (SLE), 16 had primary Sjögren's syndrome and eight had systemic sclerosis; 41 (24%) were positive for anti-Ro52/TRIM21 antibodies. Patients with anti-Ro52/TRIM21 antibodies had higher serum levels of IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP and chemokines CCL4, CXCL8, CXCL10 and CXCL12, but lower levels of complement C4. Anti-Ro52/TRIM21 antibody titers were positively correlated with IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10, and hs-CRP, and negatively with complements C3 and C4. When only SLE patients were included, no association was identified between anti-Ro52/TRIM21 antibodies and disease activity or organ-specific involvement. CONCLUSIONS: Anti-Ro52/TRIM21 antibodies are associated with aberrant cytokine circuits and elevated levels of angiogenic molecules and neutrophil and monocyte chemoattractants, which suggests an active role for these antibodies in SARD.

INTRODUCCIÓN: Los anticuerpos anti-Ro52/TRIM21 son marcadores de varias enfermedades reumáticas autoinmunes sistémicas (ERAS). OBJETIVO: Evaluar si los anticuerpos anti-Ro52/TRIM21 están relacionados con anomalías en los circuitos inflamatorios. MÉTODOS: Estudio transversal de pacientes consecutivos y ambulatorios con ERAS. Los anticuerpos anti-Ro52/TRIM21 y la proteína amiloide sérica se midieron mediante ELISA; los paneles para 18 citocinas y nueve quimiocinas se analizaron en una plataforma de lectura Luminex; la proteína C reactiva (hs-CRP) y el complemento se midieron mediante nefelometría. RESULTADOS: Se incluyeron 167 pacientes, 143 con lupus eritematoso sistémico (LES), 16 con síndrome de Sjögren primario y ocho con esclerosis sistémica; 41 fueron positivos para anticuerpos anti-Ro52/TRIM21 (24 %). Los pacientes con anticuerpos anti-Ro52/TRIM21 tuvieron niveles séricos más altos de IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP y quimiocinas CCL4, CXCL8, CXCL10 y CXCL12; y más bajos de complemento C4. Los títulos de anticuerpos anti-Ro52/TRIM21 correlacionaron positivamente con IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10 y hs-CRP; y negativamente con complemento C3 y C4. Al incluir solo LES, no se identificó asociación entre los anticuerpos anti-Ro52/TRIM21 y la actividad de la enfermedad o la afectación específica de órganos. CONCLUSIONES: Los anticuerpos anti-Ro52/TRIM21 se asocian a circuitos aberrantes de citocinas y niveles elevados de moléculas angiogénicas y quimioatrayentes de neutrófilos y monocitos, lo que sugiere un papel activo de esos anticuerpos en las ERAS.

Los anticuerpos anti-Ro52/TRIM21 están asociados a circuitos inflamatorios aberrantes en pacientes con enfermedades reumáticas autoinmunes sistémicas / Anti-Ro52/TRIM21 antibodies are associated with aberrant inflammatory circuits in patients with systemic autoimmune rheumatic diseases

Resumen Introducción: Los anticuerpos anti-Ro52/TRIM21 son marcadores de varias enfermedades reumáticas autoinmunes sistémicas (ERAS). Objetivo: Evaluar si los anticuerpos anti-Ro52/TRIM21 están relacionados con anomalías en los circuitos inflamatorios. Métodos: Estudio transversal de pacientes consecutivos y ambulatorios con ERAS. Los anticuerpos anti-Ro52/TRIM21 y la proteína amiloide sérica se midieron mediante ELISA; los paneles para 18 citocinas y nueve quimiocinas se analizaron en una plataforma de lectura Luminex; la proteína C reactiva (hs-CRP) y el complemento se midieron mediante nefelometría. Resultados: Se incluyeron 167 pacientes, 143 con lupus eritematoso sistémico (LES), 16 con síndrome de Sjögren primario y ocho con esclerosis sistémica; 41 fueron positivos para anticuerpos anti-Ro52/TRIM21 (24 %). Los pacientes con anticuerpos anti-Ro52/TRIM21 tuvieron niveles séricos más altos de IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP y quimiocinas CCL4, CXCL8, CXCL10 y CXCL12; y más bajos de complemento C4. Los títulos de anticuerpos anti-Ro52/TRIM21 correlacionaron positivamente con IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10 y hs-CRP; y negativamente con complemento C3 y C4. Al incluir solo LES, no se identificó asociación entre los anticuerpos anti-Ro52/TRIM21 y la actividad de la enfermedad o la afectación específica de órganos. Conclusiones: Los anticuerpos anti-Ro52/TRIM21 se asocian a circuitos aberrantes de citocinas y niveles elevados de moléculas angiogénicas y quimioatrayentes de neutrófilos y monocitos, lo que sugiere un papel activo de esos anticuerpos en las ERAS.

Abstract Introduction: Anti-Ro52/TRIM21 antibodies are markers for several systemic autoimmune rheumatic diseases (SARD). Objective: To assess whether anti-Ro52/TRIM21 antibodies are related to abnormalities in inflammatory circuits. Methods: Cross-sectional study of consecutive outpatients with SARD. Anti-Ro52/TRIM21 antibodies and serum amyloid A protein were measured by ELISA; panels for 18 cytokines and nine chemokines were analyzed on a Luminex reading platform, while high-sensitivity C-reactive protein (hs-CRP) and complement were measured by nephelometry. Results: Among 167 included patients, 143 had systemic lupus erythematosus (SLE), 16 had primary Sjögren's syndrome and eight had systemic sclerosis; 41 (24%) were positive for anti-Ro52/TRIM21 antibodies. Patients with anti-Ro52/TRIM21 antibodies had higher serum levels of IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP and chemokines CCL4, CXCL8, CXCL10 and CXCL12, but lower levels of complement C4. Anti-Ro52/TRIM21 antibody titers were positively correlated with IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10, and hs-CRP, and negatively with complement C3 and C4. When only SLE patients were included, no association was identified between anti-Ro52/TRIM21 antibodies and disease activity or organ-specific involvement. Conclusions: Anti-Ro52/TRIM21 antibodies are associated with aberrant cytokine circuits and elevated levels of angiogenic molecules and neutrophil and monocyte chemoattractants, which suggests an active role for these antibodies in SARD.

Association between interleukin-6 and lower urinary tract symptoms of benign prostatic hyperplasia.

OBJECTIVE: To evaluate the association between IL-6 in prostatic tissue/blood sample and BPH-LUTS, so as to preliminarily discover an indicator of inflammation that could show the severity of LUTS. PATIENTS AND METHODS: The prostatic tissues and blood samples were collected from 56 patients who underwent transurethral plasmakinetic resection of the prostate (TUPKRP). The association between IL-6 detected on prostatic tissues/blood sample and LUTS parameters, including international prostate symptom score (IPSS), peak flow rate (Qmax) and urodynamic parameters were analyzed with SPSS version 18.0, and p-value <0.05 was chosen as the criterion for statistical significance. RESULTS: The TPSA and prostate volume (PV) were found to be higher in the inflammation group (p=0.021, 0.036). There was a positive association between prostate tissue inflammation and LUTS ([IPSS, storage symptoms score (SSS), voiding symptoms score (VSS), p<0.05], [Qmax, p=0.025], [obstruction, p=0.027] and [AUR, p=0.018]). The level of serum IL-6 was significantly higher in inflammatory group (p=0.008). However, no differences were observed in different degrees of inflammation (p=0.393). The level of IL-6 in prostatic tissue significantly increased with the degree of inflammation (p<0.001), and the intensity of IL-6 expression was statistically correlative with the degree of inflammation (p<0.001). The IL-6 expression in prostatic tissue was statistically relevant with IPSS (p=0.018) and SSS (p=0.012). CONCLUSION: IL-6 expression in prostatic tissue is associated with storage IPSS, suggesting chronic inflammation might contribute to storage LUTS.

Effect of a single resistance exercise session on inflammatory markers and oxidative stress in women living with HIV / Efeito de uma única sessão de exercício resistido sobre marcadores inflamatórios e estresse oxidativo em mulheres vivendo com hiv

ABSTRACT People living with HIV (PLH), who use antiretroviral therapy (ART), are more susceptible to changes in the inflammatory profile and oxidative stress, and women have greater access to ART. Although physical exercise is a complementary strategy to treatment due to its antioxidant and anti-inflammatory effects, it is not clear whether acute responses to exercise can be harmful to PLH. The aim of the study was to investigate the acute effect of resistance exercise (RE) on inflammatory and oxidative stress markers in PLH. Ten women, using ART, performed RE session consisting of seven exercises for the whole body. For biochemical evaluation, blood samples were collected before (pre), 1 hour (1h) and 2 hours (2h) after the RE session. One-way ANOVA followed by Bonferroni's post hoc test was used to compare results between time points. There was an increase only in markers, GSSG of 160% (pre: 0.40 ± 0.11; 1h: 1.18 ± 0.36; 2h: 1.04 ± 0.25 mmol/g), TNF-α of 98 % (pre: 4.60 ± 0.55; 1h: 6.95 ± 0.77; 2h: 9.10 ± 1.03 pg/ml) and 52% IL-6 (pre: 2.47 ± 0 .67; 1h: 3.63 ± 1.26; 2h: 5.38 ± 2.15 pg/ml). The other variables remained unchanged (P > 0.05). It is concluded that a RE session increased the levels of inflammatory markers and oxidative stress in PLH in a non-exacerbated way.

RESUMO Pessoas vivendo com HIV (PVH), que utilizam a terapia antirretroviral (TARV), são mais suscetíveis a alterações no perfil inflamatório e estresse oxidativo, sendo que as mulheres possuem maior acesso à TARV. Embora o exercício físico seja uma estratégia complementar ao tratamento devido aos seus efeitos antioxidantes e anti-inflamatórios, não está claro se as respostas agudas ao exercício podem ser prejudiciais às PVH. O objetivo do estudo foi investigar o efeito agudo de exercícios com pesos (EP) sobre marcadores inflamatórios e de estresse oxidativo em PVH. Dez mulheres, em uso da TARV, realizaram uma sessão de EP constituída por sete exercícios para o corpo todo. Para avaliação bioquímica, amostras de sangue foram coletadas antes (pré), 1 hora (1h) e 2 horas (2h) após a sessão de EP. A ANOVA one-way seguida do teste post hoc de Bonferroni foi utilizada para comparação dos resultados entre os momentos. Houve aumento apenas nos marcadores, GSSG de 160% (pré: 0,40 ± 0,11; 1h: 1,18 ± 0,36; 2h:1,04 ± 0,25 mmol/g), TNF-α de 98% (pré: 4,60 ± 0,55; 1h: 6,95 ± 0,77; 2h: 9,10 ± 1,03 pg/ml) e IL-6 de 52% (pré: 2,47 ± 0,67; 1h: 3,63 ± 1,26; 2h: 5,38 ± 2,15 pg/ml). As demais variáveis permaneceram sem alterações (P > 0,05). Conclui-se que uma sessão de EP aumentou os níveis de marcadores inflamatórios e estresse oxidativo em PVH de forma não exacerbada.

Cytokine hemoadsorption with CytoSorb® in patients with sepsis: a systematic review and meta-analysis / Hemoadsorção de citocinas com CytoSorb® em pacientes com sepse: revisão sistemática e metanálise

ABSTRACT Objective: To analyze the effect of CytoSorb® on mortality, interleukin levels, vasopressor use and adverse events in patients with sepsis. Methods: We searched MEDLINE®, Embase and the Cochrane Library for randomized controlled trials and cohort studies that reported the use of CytoSorb® among septic patients. The primary outcome was mortality, and secondary outcomes included the use of vasopressors, levels of inflammatory markers, predicted versus observed mortality, length of stay in the intensive care unit, and adverse events. Results: We included 6 studies enrolling 413 patients, and assessment for risk of bias indicated variations in study quality from high to moderate. The overall mortality rate was 45%, and no significant effect on mortality was found at 28 - 30 days (RR 0.98 [0.12 - 8.25] for the randomized clinical trial and RR 0.74 [0.49 - 1.13] for cohort studies). We did not perform a metanalysis for other outcomes due to the small number of studies found or the lack of data. Conclusion: Our study found very low certainty evidence, due to imprecision, risk of bias, and heterogeneity, thereby showing no benefit of CytoSorb® use in terms of mortality at 28 - 30 days. We cannot recommend the use of CytoSorb® in septic or septic shock patients outside clinical trials. Further high-quality randomized trials with a common intervention arm are needed to evaluate the influence of CytoSorb® in this population. PROSPERO register: CRD42021262219

RESUMO Objetivo: Analisar o efeito de CytoSorb® na mortalidade, nos níveis de interleucina, no uso de vasopressores e nos eventos adversos em pacientes com sepse. Métodos: Pesquisamos o MEDLINE®, o Embase e a Biblioteca Cochrane em busca de ensaios clínicos randomizados e estudos de coorte que relatassem o uso de CytoSorb® em pacientes com sepse. O desfecho primário foi a mortalidade, e os desfechos secundários incluíram uso de vasopressores, níveis de marcadores inflamatórios, mortalidade prevista versus observada, tempo de internação na unidade de terapia intensiva e eventos adversos. Resultados: Incluímos 6 estudos com 413 pacientes, e a avaliação do risco de viés indicou variações na qualidade do estudo de alta a moderada. A taxa de mortalidade geral foi de 45%, e não foi encontrado efeito significativo na mortalidade entre 28 e 30 dias (risco relativo de 0,98 [0,12 - 8,25] para o ensaio clínico randomizado e de 0,74 [0,49 - 1,13] para estudos de coorte). Não realizamos metanálise para outros desfechos, devido ao pequeno número de estudos encontrados ou à carência de dados. Conclusão: Nosso estudo encontrou evidências de certeza muito baixa, devido à imprecisão, ao risco de viés e à heterogeneidade, demonstrando nenhum benefício no uso de CytoSorb® em termos de mortalidade em 28 a 30 dias. Não podemos recomendar o uso de CytoSorb® em pacientes com sepse ou choque séptico fora dos estudos clínicos. São necessários mais estudos randomizados de alta qualidade com um braço de intervenção comum para avaliar a influência de CytoSorb® nessa população. Registro PROSPERO: CRD42021262219

Serum lymphocytes and cytokines: diagnostic value and influence on the immune status in patients with pulmonary tuberculosis / Linfócitos e citocinas séricas: valor diagnóstico e influência no estado imunológico de pacientes com tuberculose pulmonar

ABSTRACT Objective: To determine the absolute number of serum T lymphocytes and cytokine levels and the characteristics of patients with active pulmonary tuberculosis and to assess their effect on the immune status of these patients and their diagnostic and predictive value for tuberculosis. Methods: We included 1,069 patients with active tuberculosis, 51 patients with latent tuberculosis infection, and 600 health individuals. Absolute serum T-lymphocyte counts and cytokine levels were quantified. Results: T lymphocytes were significantly reduced in patients with active tuberculosis when compared with healthy individuals. The immune function of patients gradually decreased with age and was stronger in female patients than in males. Th1 cells expressed higher levels of cytokines than did Th2 cells. Logistic regression analysis showed that reduced CD3+ T, CD8+ T, and NK cell counts, as well as reduced IL-4 and IFN-g expression, were independent influencing factors for active tuberculosis. ROC analysis showed that the sensitivity and specificity of absolute CD3+ T and CD8+ T lymphocyte counts and combined factors were significantly higher than were those of IL-4 and IFN-g for diagnosing active tuberculosis. Conclusions: Serum T-lymphocyte counts and cytokine levels can assess the immune status of tuberculosis patients; they are also useful biomarkers for predicting and diagnosing tuberculosis.

RESUMO Objetivo: Determinar o número absoluto de linfócitos T séricos e os níveis de citocinas séricas, bem como as características, de pacientes com tuberculose pulmonar ativa e avaliar o efeito desses no estado imunológico desses pacientes e seu valor diagnóstico e preditivo para tuberculose. Métodos: Foram incluídos 1.069 pacientes com tuberculose ativa, 51 pacientes com tuberculose latente e 600 indivíduos saudáveis. Foram realizadas a contagem absoluta de linfócitos T séricos e a quantificação de citocinas séricas. Resultados: Os linfócitos T estavam significativamente reduzidos nos pacientes com tuberculose ativa em comparação com os indivíduos saudáveis. A função imunológica dos pacientes diminuiu gradativamente com a idade e mostrou-se mais forte nas mulheres do que nos homens. As células Th1 expressaram maiores níveis de citocinas do que as células Th2. A análise de regressão logística mostrou que contagens reduzidas de células T CD3+, T CD8+ e NK e expressão reduzida de IL-4 e IFN-g foram fatores de influência independentes para tuberculose ativa. A análise ROC mostrou que a sensibilidade e especificidade dos valores absolutos de linfócitos T CD3+ e T CD8+ e de fatores combinados foram significativamente maiores do que as da IL-4 e do IFN-g para o diagnóstico da tuberculose ativa. Conclusões: A contagem de linfócitos T séricos e os níveis de citocinas séricas podem avaliar o estado imunológico de pacientes com tuberculose; também são biomarcadores úteis na predição e diagnóstico da tuberculose.