P2X and P2Y Receptor Antagonists Reduce Inflammation in ATPinduced Microglia

Background: P2 receptors have been implicated in the release of neurotransmitter and pro-inflammatory cytokines due to their response to neuroexcitatory substances in the microglia. The P2X4, P2X7 and P2Y12 receptors are involved in the development of pain behavior induced by peripheral nerve injury. However, it is not known if blocking P2X4, P2X7 and P2Y12 receptors is associated with the expression and the release of interleukin-1B (IL-1β), interleukin-6 (IL-6), or tumor necrosis factor-α (TNF-α) in cultured neonatal spinal cord microglia. Objective: For this reason, we examined the effects of P2X4, P2X7 and P2Y12 antagonists on the expression and the release of IL-1β, IL-6, and TNF-α in ATP-stimulated microglia. Methods: In this study, we observed the effect of A-740003, PSB-12062 and MRS 2395 (P2X4, P2X7 and P2Y12 receptors antagonist, respectively), on the expression and release of IL-1β, IL-6 and TNF-α by using real-time fluorescence quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results: ATP induced the increased expression of IL-1β, IL-6 and TNF-α at the level of messenger RNA (mRNA). ATP-evoked increase in IL-1β, IL-6 and TNF-α mRNA expression was inhibited by the P2X4 receptor antagonist A-740003 or P2X7 receptor antagonist PSB-12062, respectively. Similarly, ATP-evoked release of IL-1β, IL-6 and TNF-α was inhibited by A-740003 and PSB-12062. Furthermore, ATP-evoked increased expression of Iba-1, IL-1β, IL-6 and TNF-α mRNA, and release of IL-1β, IL-6 and TNF-α were nearly all blocked after co-administration of A-740003 plus PSB-12062. Finally, ATP-evoked increased gene expression and release of IL-1β, IL-6 and TNF-α were also inhibited by MRS 2395 (P2Y12 antagonist). Conclusion: These observations suggest a new clue for therapeutic strategies to treat the neuro-inflammation. (AU)

Anethole ameliorates inflammation induced by monosodium urate in an acute gouty arthritis model via inhibiting TLRs/MyD88 pathway

Objective To assess the effects of anethole on monosodium urate (MSU)-induced inflammatory response, investigate its role in acute gouty arthritis (AGA), and verify its molecular mechanism. Methods Hematoxylin and eosin staining assay and time-dependent detection of degree of ankle swelling were performed to assess the effects of anethole on joint injury in MSU-induced AGA mice. Enzyme-linked-immunosorbent serologic assay was performed to demonstrate the production levels of inflammatory factors (interleukin 1β [IL-1β], interleukin 6 [IL-6], interleukin 8 [IL-8], tumor necrosis factor α [TNF-α], and monocyte chemo-attractant protein-1 [MCP-1]) in MSU-induced AGA mice. Western blot assays were used to confirm the effects of anethole on oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activity and the activation of toll-like receptors (TLRs)–myeloid differentiation factor 88 (MyD88) pathway in MSU-induced AGA mice. Results We observed that a significant joint injury occurred in MSU-induced AGA mice. Anethole could alleviate the pathological injury of the synovium in MSU-induced AGA mice and suppressed ankle swelling. In addition, we observed that anethole could inhibit MSU-induced inflammatory response and inflammasome activation in MSU-induced AGA mice. Moreover, we discovered that anethole enabled to inhibit the activation of TLRs/MyD88 pathway in MSU-induced AGA mice. Our findings further confirmed that anethole contributed to the inhibitory effects on progression in MSU-induced AGA mice. Conclusion It confirmed that anethole ameliorated the MSU-induced inflammatory response in AGA mice in vivo via inhibiting TLRs–MyD88 pathway (AU)

Knockdown of DAPK1 attenuates IL-1B-induced extracellular matrix degradation and inflammatory response in osteoarthritis chondrocytes via regulating the p38 MAPK-signaling pathway

Objective To reveal the possible effects of death-associated protein kinase 1 (DAPK1) on the progression of osteoarthritis (OA) and the potential underlying mechanism. Methods : The expression of DAPK1 in OA and normal samples and interleukin (IL)-1β-stimulated chondrocytes was analyzed by quantitative real-time polymerase chain reaction and Immunoblot assay. Cell viability, proliferation, and apoptosis in DAPK1-knockdown cells stimulated with IL-1β were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution, 5-ethynyl-2β-deoxyuridine staining and flow cytometry. The chondrocyte degradation and inflammatory response in IL-1β-induced chondrocytes were investigated by Immunoblot analysis and enzyme-linked-immunosorbent serologic assay. In addition, the effect of DAPK1 on p38 mitogen-activated protein kinase (MAPK) activation was analyzed by immunoblot assay. Results : This study revealed that DAPK1 was highly expressed in OA patients and IL-1β-induced chondrocytes. Down-regulation of DAPK1 enhanced IL-1β-induced chondrocyte proliferation. DAPK1 knockdown inhibited IL-1β-induced chondrocyte degradation. In addition, DAPK1 depletion inhibited IL-1β-induced chondrocyte inflammation. Mechanically, it was revealed that down--regulation of DAPK1 could inhibit the p38 MAPK pathway, and therefore affected progression of OA. Conclusion : DAPK1 knockdown attenuates IL-1β-induced extracellular matrix degradation and inflammatory response in OA chondrocytes by regulating the p38 MAPK pathway (AU)

The role of the inflammasome and its related pathways in ovarian cancer

Ovarian cancer (OC) is the most lethal tumor of the female reproductive tract and one of the most prevalent causes of death among female cancer patients. The absence of suitable procedures for early diagnosis, chemoresistance, and limited surgical debulking are all contributing to poor survival in patients. Despite aggressive treatments, the majority of patients have a recurrence within 16–22 months. Inflammasomes are multimeric protein complexes that play a major role in the innate immune system and inflammation. The overexpression of inflammasome-related pathways, including NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), Absent in melanoma 2 (AIM2), caspase-1, and Interleukin (IL)-1 have been reported in OC patients and in vitro cell lines. Therefore, inflammasome-related genes and protein might have a role in OC pathogenesis. Considering the potential relationship between inflammasome and OC, this study aimed to provide a literature-based review to explain the role of inflammasome and inflammation in cancer progression in OC. (AU)

Diagnostic value of combined detection of IL-1β, IL-6, and TNF-α for sepsis-induced cardiomyopathy / Valor diagnóstico de la detección combinada de IL-1, IL-6, y TNF-α para la cardiomiopatía inducida por sepsis

Introduction:This study aimed to explore the diagnostic value and the correlation of the combined detection of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) with sepsis-induced cardiomyopathy (SIC).Patients and methods:Admitted to our hospital from January 2017 to January 2019, 96 patients with SIC (a study group) and 90 patients with sepsis (a control group) were enrolled. The three cytokines were determined and the diagnostic value of their combined detection for SIC was analyzed.Results:The cytokines were remarkably higher in the study group (p<.001). The combined detection of the three had a better diagnostic value for SIC (p<.001). The three cytokines were independent risk factors for the death of patients with SIC.Conclusion:IL-1β, IL-6, and TNF-α in SIC patients rise markedly. The combined detection of the three has a better predictive value for patients with SIC and is closely related to the patients’ prognoses, so it may be crucial in diagnosing and treating the disease. (AU)

Introducción:El objetivo de este estudio fue explorar el valor diagnóstico y la correlación de la detección combinada de interleucina-1β (IL-1β), interleucina-6 (IL-6), y factor de necrosis tumoral-α (TNF-α) con la miocardiopatía inducida por sepsis (CIS).Pacientes y métodos:Ingresados en nuestro hospital entre enero de 2017 y enero de 2019, se incluyó en el estudio a 96 pacientes con CIS (grupo de estudio) y 90 pacientes con sepsis (grupo control). Se determinaron las tres citocinas y se analizó el valor diagnóstico de su detección combinada para CIS.Resultados:Las citocinas fueron marcadamente superiores en el grupo de estudio (p<0,001). La detección combinada de las tres tuvo un mejor valor diagnóstico para CIS (p<0,001). Las tres citocinas fueron factores de riesgo independientes de la muerte de los pacientes con CIS.Conclusión:IL-1β, IL-6, y TNF-α se incrementaron considerablemente en los pacientes de CIS. La detección combinada de los tres valores tiene un mejor valor predictivo para los pacientes con CIS, y está estrechamente relacionada con los pronósticos de los pacientes, lo cual puede ser esencial para diagnosticar y tratar la enfermedad. (AU)

Antioxidant effect of p-coumaric acid on interleukin 1-Beta and tumor necrosis factor-alpha in rats with renal ischemic reperfusion / Efecto antioxidante del ácido p-cumárico sobre la interleucina 1-Beta y el factor de necrosis tumoral-alpha en ratas con reperfusión isquémica renal

BACKGROUND AND AIMS: Renal ischemia-reperfusion occurs in some clinical conditions such as kidney surgery that can leads to acute renal failure. The aim of this study was to investigate the effect of p-coumaric acid (CA) on ischemia reperfusion (I/R) injury. METHODS: Thirty rats were randomly divided into five groups; control, CA (100mg/kg), I/R, propylene glycol (10%) + I/R and CA + I/R, (n = 6 each). CA and propylene glycol were administered orally for 2 weeks. Then, the rats were subjected to bilateral renal ischemia for 45min and followed by reperfusion for 24 h. All rats were killed and kidney function tests, tissue malondialdehyde and activity of antioxidant enzymes were determined. Histopathological evaluations were also performed. In addition, renal expression of the tumor necrosis factor-alpha and interleukin-1Beta were determined using enzyme-linked immunosorbent assay and immunohistochemistry. RESULTS: CA significantly improved the Cr and BUN levels in CA + I/R group compared to I/R group (p < 0.005 and p < 0.001, respectively). Reduction of tissue superoxide dismutase, glutathione peroxidase and catalase, were significantly improved by CA (p < 0.01, p < 0.01 and p < 0.05). Treatment with CA also resulted in significant reduction in tissue MDA (p < 0.05), TNF-alpha (p < 0.001) and interleukin-1Beta expression (p < 0.001) that were increased by renal I/R. Also, the rats treated with CA had nearly normal structure of the kidney. CONCLUSIONS: The present findings suggest that, CA protects the kidneys against I/R injury via its antioxidant and anti-inflammatory effects

ANTECEDENTES Y OBJETIVOS: La isquemia-reperfusión renal se produce en algunas situaciones clínicas como la cirugía renal, y puede conducir a insuficiencia renal aguda. El objetivo de este estudio fue investigar el efecto del ácido p-cumárico (AC) en el daño por isquemia-reperfusión (I/R). MÉTODOS: Se dividió aleatoriamente a 30 ratas en 5 grupos; control, AC (100mg/kg), I/R, propilenglicol, (10%) + I/R y AC + I/R, (n = 6 cada uno). El AC y el propilenglicol se administraron por vía oral durante 2 semanas. A continuación, las ratas se sometieron a isquemia renal bilateral durante 45min, seguido de reperfusión durante 24h. Se sacrificó a todas las ratas y se determinaron los valores de la función renal, el malondialdehído tisular y la actividad de las enzimas antioxidantes. También se llevaron a cabo evaluaciones histopatológicas. Además, se determinó la expresión renal del factor de necrosis tumoral-alfa y la interleucina-1Beta mediante enzimoinmunoanálisis de adsorción e inmunohistoquímica. RESULTADOS: El AC mejoró significativamente los niveles de Cr y BUN en el grupo de AC + I/R en comparación con el grupo de I/R (p < 0,005 y p < 0,001, respectivamente). La reducción de la superóxido-dismutasa tisular, la glutatión-peroxidasa y la catalasa mejoró significativamente con el AC (p < 0,01, p < 0,01 y p <0,05, respectivamente). El tratamiento con AC también provocó una reducción significativa de la expresión del malondialdehído (MDA) tisular (p < 0,05), el TNF-alfa (p < 0,001) y la interleucina-1Beta (p < 0,001) que habían aumentada por la I/R renal. Además, las ratas tratadas con AC presentaron una estructura renal casi normal. CONCLUSIONES: Estos hallazgos sugieren que el AC protege los riñones frente al daño por I/R a través de sus efectos antioxidantes y antinflamatorios

Efecto de la suplementación con soja sobre la inflamación y ácido láctico inducido por ejercicio físico exhaustivo en ratas / Effect of supplementation with soy on inflammation and lactic acid induced by exhaustive physical exercise in rats

INTRODUCCIÓN: El ejercicio físico exhaustivo genera marcadores inflamatorios y de ácido láctico. La suplementación con sustancias naturales es motivo de análisis debido a sus escasos efectos secundarios. OBJETIVO: Determinar la respuesta inflamatoria y el nivel de ácido láctico inducidos por ejercicio físico exhaustivo después de la ingesta de soja en modelo animal. MATERIALES Y MÉTODO: Se emplearon treinta ratas macho de raza Sprawley dawley de 180 a 200 g, sanos divididos en tres grupos: sedentario (C), con ingesta de soja a prueba (E+TP) y sin ingesta de soja a prueba (E). Los grupos E+TP y E, realizaron la prueba Morris Water Maze Test. Se determinaron marcadores inflamatorios como factor de necrosis tumoral alfa (TNF-a), interleuquina 1 beta (IL-1Beta), interleuquina 6 (IL-6) en plasma mediante técnica ELISA, enzima ciclooxigenasa 2 (COX-2), óxido nítrico sintaza (iNOS) y como marcador antiinflamatorio Receptor gamma activado por proliferador de peroxisoma (PPAR-γ), el cual, se midió en músculos cuádriceps mediante técnica de Western-blot y se midió el ácido láctico en sangre. RESULTADOS: Se obtuvo una disminución significativa en plasma de los niveles inflamatorios de TNF-alfa (600 vs 350 pg/ml), IL-1Beta (450 vs 150 pg/ml), e IL-6 (480 vs 100 pg/ml), COX-2 (52 vs 25 RDU) e iNOS (58 vs 8 RDU) en el grupo E+TP en comparación con el grupo E. Además se observó un aumento de la expresión de la proteína PPAR-γ (18 vs 65 RDU) en el grupo E+TP en comparación con el grupo E. Respecto a las mediciones de ácido láctico los grupos obtuvieron valores máximos de: E:35, C:22 y E+TP:28 Mmol/Lactato, lo cual, indica que el grupo E y E+TP a pesar que se sometieron a la misma prueba, los niveles de ácido láctico son heterogéneos. CONCLUSIÓN: La ingesta de soja mitiga los niveles de ácido láctico y de marcadores inflamatorios inducidos por el ejercicio fisico exhautivo en modelo animal

INTRODUCTION: Exhautive physical exercise generates inflammatory and lactic acid markers. The supplementation with natural substances is reason for analysis due to its limited side effects. OBJECTIVE: To determine the inflammatory response and the level of lactic acid induced by exhaustive physical exercise after the ingestion of soybean in animal model. MATERIALS AND METHOD: Thirty male Sprawley dawley rats from 180 to 200 g were used, healthy divided into three groups: sedentary (C), with soybean intake tested (E+TP) and without soybean intake tested (E). The E + TP and E groups performed the Morris Water Maze Test. Inflammatory markers were determined as tumor necrosis factor alpha (TNF-a), interleukin 1 beta (IL-1β), interleukin 6 (IL-6) in plasma by ELISA technique, enzyme cyclooxygenase 2 (COX-2), nitric oxide synthase (iNOS) and as anti-inflammatory marker Peroxisome proliferator-activated receptor gamma (PPAR-γ), which was measured in quadriceps muscles by Western-blot technique and measured lactic acid in blood. RESULTS: A significant decrease in plasma was obtained in the inflammatory levels of TNF-alpha (600 vs 350 pg/ml), IL-1Beta (450 vs 150 pg/ml), and IL-6 (480 vs 100 pg/ml), COX-2 (52 vs. 25 RDU) and iNOS (58 vs. 8 RDU) in the E+TP group compared to the E group. In addition an increase in the expression of the PPAR-γ protein was observed (18 vs 65 RDU) in the group E+TP compared to group E. Regarding the measurements of lactic acid, the groups obtained maximum values of: E: 35, C: 22 and E+TP: 28 Mmol/Lactate, which indicates that Group E and E+TP although they underwent the same test, lactic acid levels are heterogeneous. CONCLUSION: The intake of soy mitigates the levels of lactic acid and inflammatory markers induced by exhautive physical exercise in animal models

Propuesta de uso de Anakinra en el distress respiratorio agudo secundario a COVID-19 / Proposal for the use of Anakinra in acute respiratory distress secondary to COVID-19

El desenlace de la infección por SARS-CoV-2 (COVID-19) afecta fundamentalmente al campo pulmonar, ocasionando un cuadro de SÍNDROME DE DISTRÉS RESPIRATORIO AGUDO (SDRA). Este proceso es un cuadro inflamatorio, protagonizado por una cascada de citocinas bajo el amparo del INFLAMOSOMA NLRP3, responsable principal de la destrucción alveolar. De entre todas las citocinas que se desencadenan en este cuadro destaca la IL beta. ANAKINRA es un potente fármaco biológico, capaz de bloquear esta IL 1 beta. Proponemos su uso, de cara a controlar el SDRA secundario a la infección por COVID-19

The outcome of the SARS-CoV-2 (COVID-19) infection fundamentally affects the lung field, causing ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS). This process is an inflammatory picture, involving an NLRP3 INFLAMOSOME-triggered cytokine storm, the main player in alveolar destruction. IL-1 beta stands out among the cytokines that are triggered in this picture. ANAKINRA is a potent biological drug, capable of blocking this IL 1 beta. We propose its use in controlling ARDS secondary to COVID-19 infection

Valor terapéutico potencial de las estrategias dirigidas contra la interleucina 1beta en la enfermedad cardiovascular ateroesclerótica / Potential therapeutic value of interleukin 1Beta-targeted strategies in atherosclerotic cardiovascular disease

Múltiples ensayos clínicos han demostrado de forma inequívoca que los medicamentos hipocolesterolemiantes disminuyen el riesgo de enfermedad cardiovascular ateroesclerótica de una muy amplia variedad de personas. A pesar de esto, muchas personas tratadas de manera óptima según los estándares actuales presentan eventos isquémicos potencialmente letales. Evidencia experimental y clínica reciente indica que la inflamación persistente en la placa ateroesclerótica es uno de los principales mecanismos subyacentes a este riesgo residual, lo que ha abierto la puerta a la aplicación de fármacos antiinflamatorios para la prevención de la enfermedad cardiovascular. En este artículo se repasa el conocimiento actual sobre la biología de la citocina interleucina 1beta, un regulador clave de la respuesta inflamatoria en la placa ateroesclerótica y la diana del primer ensayo clínico que ha demostrado que un fármaco antiinflamatorio puede reducir de forma efectiva el riesgo cardiovascular. Se discuten los importantes retos a los que se enfrentan los inhibidores de la interleucina 1beta y otros compuestos antiinflamatorios en su traslación al ámbito clínico y se identifican otras posibles dianas en esta vía de señalización, prometedoras en el contexto cardiovascular

Clinical trials have unequivocally shown that cholesterol-lowering drugs decrease the risk of atherosclerotic cardiovascular disease in an exceptionally wide range of individuals. Yet, even when treated optimally according to current standards, many individuals still experience life-threatening ischemic events. Emerging experimental and clinical evidence strongly suggests that persistent inflammation is a major driver of this residual risk, which has opened the door to the application of anti-inflammatory drugs for cardiovascular disease prevention. Here, we review our current knowledge of the biology of interleukin-1Beta, a key regulator of inflammation in atherosclerotic plaque and the target of the first clinical trial to demonstrate that an anti-inflammatory drug can effectively reduce cardiovascular risk. We discuss the challenges faced by interleukin-1Beta inhibitors and other anti-inflammatory compounds in their translation to the clinical scenario, and identify other potential targets within this signaling pathway that hold promise in the cardiovascular setting

¿Pueden ser la interleucina-2 y la interleucina-1ß biomarcadores específicos de la sintomatología negativa en la esquizofrenia? / Can interleukin-2 and interleukin-1ß be specific biomarkers of negative symptoms in schizophrenia?

Introducción: Hay evidencias que sugieren la existencia de alteraciones de algunas citocinas en pacientes con esquizofrenia, pero su asociación con la psicopatología aún no está clara. El objetivo de este estudio es determinar si los niveles de citocinas proinflamatorias (factor de necrosis tumoral-alfa, interleucina [IL]-6, IL-2, IL-1ß, IL-1RA) están aumentados en pacientes ambulatorios clínicamente estables en comparación con individuos sanos, y analizar si podrían ser biomarcadores específicos de las diferentes dimensiones clínicas de la esquizofrenia. Métodos: Se evaluaron 73 pacientes con esquizofrenia en sus primeros 10 años de evolución de la enfermedad y 73 controles sanos pareados por edad y sexo. Se realizó una evaluación precisa de las dimensiones clínicas (positiva, negativa, depresiva y cognitiva) en estos pacientes. Resultados: Solo los niveles de IL-6 están significativamente elevados en los pacientes tras controlar por índice de masa corporal, perímetro abdominal, tabaquismo y tratamiento psicofarmacológico en comparación con sus controles sanos. Tras ajustar por varios factores de confusión, los modelos de regresión lineal múltiple identificaron cómo las concentraciones de IL-1ß predicen los síntomas negativos, psicopatología general y gravedad global de la Escala del Síndrome Positivo y Negativo, mientras los niveles de IL-2 predicen el dominio motivación y placer de la Entrevista de Evaluación Clínica para Síntomas Negativos y la puntuación global en la Escala de Funcionamiento Personal y Social. Sin embargo, el rendimiento cognitivo, la gravedad de los síntomas depresivos y positivos no correlacionaron con ninguna de las citocinas. Conclusiones: Nuestros hallazgos sugieren que las concentraciones de IL-6 permanecen elevadas en pacientes estables con esquizofrenia. Mientras que la IL-2 marca específicamente la gravedad en el dominio motivación y placer de la sintomatología negativa, la IL-1ß no es específica para esta dimensión, ya que también predice la gravedad de la sintomatología general y global

Introduction: Evidence suggests the existence of cytokine disturbances in patients with schizophrenia but their association with psychopathology is still unclear. The aim of the current study was to determine if pro-inflammatory cytokine levels (tumor necrosis factor-alfa, interleukin (IL)-6, IL-2, IL-1ß, IL-1RA) are increased in stable outpatients compared with healthy subjects, and to analyze if they could be specific biomarkers of clinical dimensions in schizophrenia. Methods: We studied 73 stable outpatients with schizophrenia in their first 10 years of illness and 73 age- and sex-matched healthy controls. An accurate assessment of clinical dimensions (positive, negative, depressive, cognitive) was performed in patients. Results: Only IL-6 levels were significantly increased in patients after controlling for body mass index, waist circumference, smoking, and psychopharmacological treatment, compared with healthy subjects. After adjusting for several confounders, multiple linear regression models identified that Positive and Negative Syndrome Scale negative symptoms, general psychopathology, and global severity are predicted by IL-1ß concentrations, while motivation and pleasure domain of Clinical Assessment Interview for Negative Symptoms and Personal and Social Performance global functioning scores are predicted by IL-2 levels. Cognitive performance, positive, and depressive symptom severity did not correlate with any cytokine. Conclusions: Our findings suggested that IL-6 concentrations are elevated in stable patients with schizophrenia. Whereas IL-2 specifically marks severity of the motivation and pleasure domain of negative symptoms, IL-1ß is not specific to this dimension as it also predicts severity of general and global symptomatology

Effect of anakinra, an interleukin one beta antagonist, on oxidative testicular damage induced in rats with ischemia reperfusion / Efecto de la anakinra, que es un antagonista de la interleucina 1 beta en oxidativo daño testicular, inducida en ratas con isquemia reperfusión

It has been reported in the literature that proinflammatory interleukin-1 beta (IL-1β) is increased in cases of testicular ischemia reperfusion (I/R) damage. This information suggests that anakinra, an IL-1β antagonist, may be effective in testicular I/R damage. Objective: In our study, we investigated the effect of anakinra on testicular I/R damage induced in rats with torsion/detorsion. Methods: The 50mg/kg anakinra+testicular torsion/detorsion (KTD-50) and 100mg/kg anakinra+testicular torsion/detorsion (KTD-100) groups received an intraperitoneal (i.p.) injection of 50mg/kg and 100mg/kg of anakinra, respectively. In turn, the testicular torsion/detorsion (TTD) and sham operation (SOG) groups received a single dose of distilled water as a solvent 1h before ketamine anaesthesia. After the testes of the TTD, KTD-50 and KTD-100 groups were subjected to torsion and detorsion for 4h each, the rats were killed with a high-dose anaesthesia, and their testicles were removed and evaluated through biochemical, gene expression and histopathological examinations. The results were evaluated in comparison with those of the SOG group. Results: The levels of malondialdehyde (MDA), myeloperoxidase (MPO) and IL-1β showed significant increases in the TTD group, which underwent torsion/detorsion, compared to the KTD-50, KTD-100 and SOG groups. Conversely, the levels of glutathione (tGSH), glutathione peroxidase (GPO) and glutathione s-transferase (GST) were found to be significantly higher in the KTD-50, KTD-100 and SOG groups than in the TTD group. Conclusion: Anakinra at a 100mg/kg dose histologically suppressed better oxidative stress and tunica albuginea, germ cell, seminiferous tubule and interstitial damage in the testicular tissue compared to a 50mg/kg dose. Experimental results indicate that anakinra might be beneficial in the attenuation of testicular I/R damage

Antecedentes: Se ha reportado en la literatura que citoquinas interleuquina-1 beta (IL-1β) es mayor en el daño de la isquemia reperfusión testicular (I/R). Esta información sugiere que la anakinra, que es un antagonista IL-1β puede ser eficaz en daño testicular I/R. Objetivo: En nuestro estudio se investigó el efecto de este medicamento en daño testicular I/R inducida en ratas con detorsion/torsión. Métodos: KTD-50 grupo recibido intraperitonealmente (i.p.) inyección de 50mg/kg y KTD-100 Grupo 100mg/kg de anakinra, mientras TTD (control) y SOG (sham grupo operación) recibieron una dosis única de agua destilada como solvente, una hora antes de ketamina anestesia. Después de que los testículos de TTD, KTD-50 y KTD-100 grupos fueron sometidas a torsión y detorsion para cuatro por cuatro horas, las ratas fueron asesinados con altas dosis de anestesia, sus testículos fueron extraídos y evaluados a través de la expresión génica, bioquímicas e histopatológicas de exámenes. Los resultados fueron evaluado en comparación con la de SCG grupo. Resultados: Los niveles de MDA, MPO y IL- 1β mostraron incrementos significativos en el grupo TTD/torsión detorsion administrados frente a-50, KTD KTD-100 y SOG grupos. Por el contrario, los niveles de tGSH, GPO y GST resultaron significativamente más altas en KTD-50 KTD-100 y grupos SOG de TTD en grupo. Conclusión: La anakinra en 100mg/kg dosis mejor histológicamente suprime el estrés oxidativo y la túnica albuginea, células germinales, túbulos seminíferos apretadamente enrollados intersticial y daño en el tejido testicular en comparación con la dosis de 50mg/kg. Los resultados experimentales indican que la anakinra puede ser beneficiosa en la atenuación de los daños I/R testicular

Eficacia de anakinra como tratamiento de la pericarditis recurrente / Efficacy of anakinra as a treatment for recurrent pericarditis

No disponible

La interleucina-1Beta aumenta la muerte neuronal en el giro dentado del hipocampo asociada al estado epiléptico en la rata en desarrollo / Interleukin-1Beta increases neuronal death in the hippocampal dentate gyrus associated with status epilepticus in the developing rat

Introducción: La interleucina 1β (IL-1Beta) aumenta la muerte neuronal necrótica debido al estado epiléptico (EE) en el área CA1 del hipocampo de ratas en desarrollo; sin embargo, se desconoce si ejerce un efecto similar en el giro dentado (GD) hipocampal. El objetivo de esta investigación fue analizar el efecto de IL-1Beta en la muerte neuronal inducida por el EE en el GD de ratas Wistar de 14 días de edad. Métodos: El EE se indujo con el modelo de litio-pilocarpina. Seis horas después del inicio del EE, la IL-1Beta se inyectó intracerebroventricularmente (0, 0,3, 3, 30 o 300 ng/μl); grupos adicionales se inyectaron con el antagonista natural del receptor tipoi (IL-1RI) de IL-1Beta (IL-1Ra, 30 ng/μl) en ausencia o presencia de IL-1Beta (3 ng/μl). La muerte neuronal se evaluó en la capa granular del GD 24 h después del EE mediante la tinción de hematoxilina-eosina. Las células muertas se caracterizaron por presentar citosol eosinofílico y núcleos condensados y fragmentados. Resultados: Se observó un incremento en el número de células eosinofílicas en el GD ipsilateral a la inyección de 3 y 300 ng/μl de IL-1Beta en comparación con el grupo vehículo; en el GD contralateral se observó un efecto similar únicamente con 3 ng/μl de IL-1Beta. La coadministración de IL-1Beta con el IL-1Ra no evitó el aumento en el número de células eosinofílicas. Conclusión: La IL-1Beta aumenta la muerte neuronal con morfología apoptótica provocada por el EE en el GD del hipocampo, mecanismo independiente de la activación del receptor IL-1RI (AU)

Background: Interleukin-1Beta (IL-1Beta) increases necrotic neuronal cell death in the CA1 area after induced status epilepticus (SE) in developing rats. However, it remains uncertain whether IL-1Beta has a similar effect on the hippocampal dentate gyrus (DG). In this study, we analysed the effects of IL-1Beta on 14-day-old Wistar rats experiencing DG neuronal death induced by SE. Methods: SE was induced with lithium-pilocarpine. Six hours after SE onset, a group of pups was injected with IL-1β (at 0, 0.3, 3, 30, or 300 ng/μL) in the right ventricle; another group was injected with IL-1Beta receptor (IL-1R1) antagonist (IL-1Ra, at 30 ng/μL) of IL-1RI antagonist (IL-1Ra) alone, and additional group with 30 ng/μL of IL-1Ra plus 3 ng/μL of IL-1Beta. Twenty-four hours after SE onset, neuronal cell death in the dentate gyrus of the dorsal hippocampus was assessed using haematoxylin-eosin staining. Dead cells showed eosinophilic cytoplasm and condensed and fragmented nuclei. Results: We observed an increased number of eosinophilic cells in the hippocampal DG ipsilateral to the site of injection of 3ng/μL and 300 ng/μL of IL-1Beta in comparison with the vehicle group. A similar effect was observed in the hippocampal DG contralateral to the site of injection of 3 ng/μL of IL-1Beta. Administration of both of IL-1Beta and IL-1Ra failed to prevent an increase in the number of eosinophilic cells. Conclusion: Our data suggest that IL-1Betaincreases apoptotic neuronal cell death caused by SE in the hippocampal GD, which is a mechanism independent of IL-1RI activation (AU)

Critical role of regulator of calcineurin 1 in spinal cord injury

Spinal cord injury (SCI) is a severe clinical problem worldwide. The pathogenesis of SCI is complicated and much is unknown. The current study was designed to investigate the possible role of regulator of calcineurin 1 (RCAN1) in SCI and to explore the possible molecular mechanisms. Rats were injected with LVshRNAi-RCAN1 and then contusion-induced SCI was established. We found that RCAN1 was significantly increased in spinal cord of rats with SCI. Knockdown of RCAN1 markedly facilitated the structural and functional recovery in the spinal cord, as illustrated by decrease of lesion volume and increase of Basso, Beattie, and Bresnahan (BBB) and combined behavioral score (CBS) scores. Downregulation of RCAN1 suppressed the increase of pro-inflammatory cytokines, including IL-1β and TNF-α, and inhibited the increase of TUNEL-positive cell numbers and caspases 3 and 9 activities. The decrease of oxygen consumption rate and increase of expression of glucose-regulated protein 78 (GRP78) and phosphorylation of protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) in rats with SCI were inhibited by LVshRNAi-RCAN1. Moreover, knockdown of RCAN1 ameliorated oxidative stress in rats with SCI, as evidenced by decrease of TBA reactive substances (TBARS) and GSSG content and increase of glutathione (GSH) level. These results suggested that RCAN1 played an important role in SCI through regulation of various pathological processes. Overall, the data provide novel insights into the role of RCAN1 in SCI and novel therapeutic targets of the treatment of injury in the spinal cord (AU)

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The impact of the IL-1B, IL-1Ra, IL-2, IL-6 and IL-10 gene polymorphisms on the development of Behcet's disease and their association with the phenotype / Impacto de los polimorfismos genéticos de IL-1 beta, IL-1Ra, IL-2, IL-6 e IL-10 en el desarrollo de la enfermedad de Behcet y su asociación con el fenotipo

Background and objective: This trial was designed to investigate the effects of the interleukin (IL)-1β, IL-1Ra, IL-2, IL-6, IL-10 gene polymorphisms on Behcet's disease (BD) occurrence and the association between the polymorphisms and the phenotype. Materials and method: The study population consisted of 71 patients and 70 age and gender-matched healthy subjects. Each of the participants had 2cc of blood withdrawn, which was placed into a whole blood tube, and the DNA was obtained using the NucleoSpin® Blood DNA Isolation kit. To display the band lengths, the products were amplified using the primary pairs of the interleukins investigated and developed in a 2% agarose gel. Results: There were no significant differences between the groups with respect to the IL-1Ra, IL-1β, IL-2, IL-6 and the IL-10 gene polymorphism distributions. In the patient group the IL-1RN2 gene polymorphism was detected to be statistically correlated with the presence of articular involvement (p = 0.0283) and the IL-1β gene polymorphism was statistically correlated with the presence of an ocular lesion (p = 0.0178). The evaluation of the IL-2 gene polymorphism (p = 0.0065) and IL-10 gene polymorphism (p = 0.0483) distributions with respect to age of BD onset revealed a statistically significant distribution. Conclusion: The statistical correlations between the articular involvement and IL-1RN, the ocular involvement and the IL-1β, and the age of disease onset and the IL-2 and IL-10 gene polymorphisms, detected for the first time in the literature, suggest that these polymorphisms could be statistically associated with the disease symptoms and used as prognostic factors (AU)

Fundamento y objetivo: Este estudio fue designado para investigar los efectos de los polimorfismos genéticos de interleucina (IL)-1β, IL-1Ra, IL-2, IL-6 e IL-10 en la ocurrencia de la enfermedad de Behcet (EB) y la asociación entre los polimorfismos y el fenotipo. Materials y método: La población de estudio consistió en 71 pacientes y 70 sujetos sanos emparejados por edad y sexo. A cada participante se le extrajeron 2cc de sangre y el ADN se obtuvo usando el kit NucleoSpin® Blood DNA Isolation. Para mostrar las longitudes de las bandas, los productos fueron amplificados usando los primeros pares de las IL investigadas y se desarrollaron en un gel de agarosa al 2%. Resultados: No hubo diferencias significativas entre los grupos en relación con las distribuciones de los polimorfismos genéticos de IL-1Ra, IL-1β, IL-2, IL-6 e IL-10. En el grupo de pacientes, el polimorfismo genético de IL-1RN2 detectado se correlacionó estadísticamente con la presencia de afección articular (p = 0,0283), y el polimorfismo genético de IL-1β se correlacionó estadísticamente con la presencia de lesión ocular (p = 0,0178). La evaluación de la distribución del polimorfismo genético de IL-2 (p = 0,0065) e IL-10 (p = 0,0483) en relación con la edad de inicio de la EB reveló una distribución estadísticamente significativa. Conclusión: La correlación estadística entre afección articular e IL-1RN, afección ocular e IL-1β, y la edad de inicio de la enfermedad y los polimorfismos genéticos de IL-2 e IL-10, detectados por primera vez en la literatura médica, evidencian que estos polimorfismos se asociaron estadísticamente a los síntomas de la enfermedad y se podrían usar como factores pronósticos (AU)

Anakinra induce la remisión completa del síndrome nefrótico en un paciente con fiebre mediterránea familiar y amiloidosis / Anakinra induces complete remission of nephrotic syndrome in a patient with familial mediterranean fever and amyloidosis

La amiloidosis renal es una de las complicaciones más graves de la fiebre mediterránea familiar (FMF). La colchicina ha reducido la incidencia de esta complicación, que ahora solo aparece en pacientes no tratados, tratados de manera insuficiente o resistentes al fármaco. No obstante, la colchicina se ha mostrado poco eficaz en pacientes que inician el tratamiento cuando la amiloidosis ya está presente. En este trabajo presentamos el caso de un enfermo con FMF y amiloidosis renal secundaria diagnosticada mediante biopsia renal que desarrolló un síndrome nefrótico completo a pesar del tratamiento con colchicina. Por la mala evolución del cuadro se decidió iniciar tratamiento con anakinra (un inhibidor de la interleucina 1Beta). En los meses posteriores a la instauración del fármaco el enfermo presentó una mejoría progresiva del síndrome nefrótico, hasta alcanzar la remisión completa. La función renal permaneció estable. Los inhibidores de la interleucina 1Beta pueden ser un tratamiento efectivo de la FMF en pacientes con amiloidosis renal secundaria (AU)

Renal amyloidosis is one of the most severe complications of familial Mediterranean fever (FMF). Colchicine has reduced the incidence of this complication, which now only appears in untreated, under-treated and resistant patients, but it is usually ineffective in patients with advanced amyloidosis. Here we report a patient with FMF and biopsy-proven amyloidosis who presented with nephrotic syndrome despite colchicine treatment. Anakinra (an interleukin-1Beta inhibitor) was started and a dramatic complete remission of nephrotic syndrome was observed in the following months. Anakinra can be an effective treatment for FMF patients with severe secondary amyloidosis (AU)

Evaluación del daño tisular producido por la nefrolitotomía percutánea mediante la determinación sérica de mediadores inflamatorios / Assessment of tissue damage due to percutaneous nephrolithotomy using serum concentrations of inflammatory mediators

Objetivo: Determinar los efectos producidos por la nefrolitotomía percutánea (NLP) sobre los tejidos mediante la cuantificación de mediadores de respuesta inflamatoria, así como la influencia del desarrollo de complicaciones postoperatorias en el daño tisular. Pacientes y métodos: Estudio observacional, prospectivo, no aleatorizado en 40 pacientes intervenidos mediante NLP. Como grupo control se empleó una cohorte de 50 pacientes con litiasis renal tratada con litotricia extracorpórea por ondas de choque. Determinación previa al tratamiento (T0) y a las 2, 6 y 24 h (T1, T2 y T3) de interleuquina-1beta (IL-1β), factor de necrosis tumoral-alfa (TNF-α), interleuquina-6 (IL-6) y proteína C-reactiva (PCR). Resultados: No se observaron cambios en los niveles de IL-1β y TNF-α. IL-6 presentó un pico sérico entre las 2 y 6 h de la NLP (mediana de 17,8 y 15,8 pg/ml, respectivamente), mientras que el valor pico de PCR fue de 3,4 mg/l a las 24 h. En el grupo tratado con litotricia expracorpórea por ondas de choque no se apreciaron variaciones significativas en ninguno de los marcadores. La concentración sérica de IL-6 y PCR a las 24 horas post-NLP es diferente en función de la aparición de complicaciones (p = 0,001 y p = 0,039, respectivamente). IL-6 presentó una buena capacidad predictiva para el desarrollo de complicaciones (AUC de 0,801). Conclusiones: El daño tisular producido por la NLP es de baja intensidad. Este daño aumenta significativamente en aquellos casos que desarrollan complicaciones en el postoperatorio. La determinación de IL-6 a las 24 h post-NLP parece ser un buen marcador predictivo para el desarrollo de complicaciones (AU)

Objectives: To determine the percutaneous nephrolithotomy (PCNL) effects on the tissues using the quantification of inflammatory mediators, and to assess their impact on the development of postoperative complications. Patients and methods: Prospective observational non-randomized study on 40 patients underwent to PCNL. 50 patients with kidney stone who were treated by extracorporeal shock wave lithotripsy (ESWL) were used as control group. Interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were determined at baseline (T0: before treatment), and at 2, 6 and 24 hours after (T1, T2 and T3). Results: No relevant changes on IL-1β and TNF-α were found. IL-6 showed two peaks at 2 and 6hours post-PCNL (median 17.8 and 15.8 pg/mL, respectively). At 24hours CRP had reached its peak value (3.4mg/L). The group treated with ESWL no showed significant changes in any of the markers. The serum concentration of IL-6 and CRP at 24 hours post-NLP is different depending on the occurrence of complications (P = .001 and P = .039, respectively). IL-6 showed a good predictive power for the development of complications (AUC .801). Conclusions: Tissue damage caused by the PCNL is low. This damage increases significantly in those cases showing postoperative complications. IL-6 at 24 hours has been shown to be a good predictive tool for the development of complications

Effects of glucosamine-chondroitin combination on synovial fluid IL-1beta, IL-6, TNF-alfa and PGE2 levels in internal derangements of temporomandibular joint

BACKGROUND: The aim of the present study was to evaluate the effects of glucosamine-chondroitin sulphate combination on internal derangements of temporomandibular joint in clinical and biochemical manners. MATERIAL AND METHODS: This randomized clinical study included 31 cases reporting joint tenderness, in which disc displacement was detected on MR imaging. In all patients, synovial fluid sampling was performed under local anesthesia. In the study group, the patients were prescribed a combination of 1500 mg glucosamine and 1200 mg chondroitin sulphate, while patients in the control group were only prescribed 50 mg tramadol HCl (twice daily) for pain control. After 8 weeks, synovial fluid sampling was repeated in the same manner. The levels of pain, maximum mouth opening (MMO), synovial fluid IL-1ß, IL-6, TNF-alfa and PGE2 measured before and after pharmacological intervention were compared. RESULTS: The reduction in pain levels was significant in both groups. There was no significant difference between two groups in terms of pain reduction. The improvement in MMO was significant in the study group but it was not in the control group. The MMO improvement was significantly higher in the study group compared to the control group. In the study group, significant decrease was observed in PGE2 level, while the decreases in IL-1beta, IL-6 and TNF-alfa levels were not significant. In the control group, no significant decrease was observed in any of the inflammatory cytokines after 8 weeks, moreover IL-1ß and IL-6 levels were increased. Alterations of IL-1ß and IL-6 levels were significant in study group while TNF-alfa and PGE2 levels were not, compared to control group. CONCLUSIONS: In conclusion, these results might suggest that glucosamine-chondroitin combination significantly increases the MMO and decreases the synovial fluid IL1beta and IL6 levels in internal derangements of TMJ compared to tramadol. The modifications of synovial fluid TNF-α and PGE2 levels do not reach statistical significance. This combination also provides efficient pain relief in similar level with tramadol, a narcotic analgesic

Arterioesclerosis sistemica precoz y enfermedad autoinflamatoria / Early systemic atherosclerosis and autoinflammatory disease

Las enfermedades autoinflamatorias sistémicas (EAS) se caracterizan por la presencia de episodios inflamatorios agudos, recurrentes o persistentes, en los cuales no se evidencian causas autoinmunitarias, infecciosas o neoplásicas. La inflamación a nivel sistémico se ha relacionado con el desarrollo y progresión de la arterioesclerosis. En el caso del síndrome de Muckle Wells (SMW), la inflamación vendría determinada por una hiperactivación de la interleucina-1β (IL-1β). Exponemos un caso clínico en donde se describen las complicaciones vasculares asociadas a arterioesclerosis precoz en el SMW

Systemic autoinflammatory diseases (SAD) are characterized by the presence of acute, recurrent or persistent inflammatory episodes, in which autoimmune, infectious or neoplastic causes are not evidenced. Systemic inflammation has been linked to development and progression of atherosclerosis. In the case of the Muckle Wells Syndrome (MWS), inflammation would be determined by hyperactivation of interleukin 1β (IL-1β). We present a case report in which vascular complications associated with early atherosclerosis in the MWS are described