Effect of intraneural injection of diosmetin combined with lidocaine on sciatic nerve block in retired players

Objective: To investigate the effect and mechanism of intraneural injection of diosmetin combined with lidocaine on sciatic nerve block in retired players. Methods: Thirty two retired players were randomly divided into four groups: Sham group, diosmetin group (100mg·kg-1) and lidocaine group (10% lidocaine (20μL)) and lidocaine+diosmetin group (10% lidocaine (20μL) and 100mg·kg-1 diosmetin). Then the conduction state of sciatic nerve was detected; The sensory and motor function were assessed; the histopathological changes of sciatic nerve were observed by toluidine blue staining; the gene expression of IL-1βand TNF- α on the mRNA level was detected by RT-PCR. Results: Compared with lidocaine group, lidocaine+diosmetin can better enhance sensory and motor nerve block, reduce histopathological damage of sciatic nerve, and decrease the expression of inflammatory factors, such as IL-1 β And TNF- α in transcriptional level. Conclusion: Diosmetin has the effects of enhancing sensory and motor nerve block, anti-inflammatory and protecting nerve injury. (AU)

Correlation analysis of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in refractory chronic rhinosinusitis: A retrospective study

Objective: To investigate the potential correlation of transforming growth factor-β (TGF-β), matrix metalloprotein 9 (MMP-9), tissue inhibitor of metalloproteinases 1 (TIMP-1), Interleukin 1 (IL-1), IL-4, IL-6, IL-17, and tumor necrosis factor alpha (TNF-α) in refractory chronic rhinosinusitis.Methods: A total of 150 participants were retrospectively included in this study from August 2018 to February 2020. The people enrolled were equally allocated into refractory group (patients with refractory chronic rhinosinusitis), chronic group (patients with chronic rhinosi-nusitis), and control group (normal people). The level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α were recorded. The unconditional multivariate binary logistic regression was used to analyze the factors affecting refractory chronic rhinosinusitis.Results: The Davos score, T&T olfactometer threshold test, and Lund-Mackay CT scores in refractory group were significantly higher than the chronic group (P<0.05). The level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in the refractory group were significantly higher than the chronic group and the control group (all P<0.05). Similarly, the level of the above mentioned indexes in the chronic group were significantly higher than the control group (P<0.05). The Davos score, T&T olfactometer threshold test score, Lund-Mackay CT score, and the level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α positively correlated with refractory chronic rhinosinusitis. Moreover, the unconditional multivariate binary logistic regression showed that the influencing factors of refractory chronic rhinosinusitis included TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α.Conclusion: The findings of the present study provide evidence for TGF-β1, MMP-9, TIMP-1, IL-4, IL-6, IL-17, and TNF-α as the influencing factors of refractory chronic rhinosinusitis (AU)

Baseline renal functions predict the effect of canakinumab on regression of proteinuria in patients with familial Mediterranean fever / Las funciones renales iniciales predicen el efecto del canakinumab en la regresión de la proteinuria en pacientes con fiebre mediterránea familiar

Introduction and objectives: Canakinumab, an IL-1 blocking drug, decreases the frequency and severity of the attacks and decreases the proteinuria level in colchicine resistant/intolerant familial Mediterranean fever (FMF) patients. However, it is not known whether patients with impaired or preserved renal functions respond differently to IL-1 blocking therapies in terms of proteinuria reduction and progression of kidney dysfunction which was the aim of this study. Materials and methods: Adult FMF subjects with biopsy proven amyloidosis who had 24-h urine protein excretion>150mg/day before initiation of canakinumab were divided into two groups as patients with preserved renal function (GFR≥60mL/min) and patients with impaired renal function (GFR<60mL/min). The response in proteinuria and renal functions are compared between two groups in this cross-sectional study. Results: A total of 18 patients (11 with preserved and 7 with impaired renal function) were included in this study. Although proteinuria levels of both groups were similar at the baseline and at six months after initiation of canakinumab, proteinuria at 12 months was significantly lower for patients with preserved renal function compared to patients with impaired renal function (2462±1760mg/day vs. 7065±3035mg/day respectively, p=0.02). All of the patients with preserved renal function had more than 50% decrease in proteinuria at 12 months compared to baseline values, while none of the patients with impaired renal function had more than 50% decrease in proteinuria. (AU)

Introducción y objetivos: El canakinumab, un fármaco bloqueante de la IL-1, disminuye la frecuencia y la gravedad de los ataques y reduce el nivel de proteinuria en pacientes con fiebre mediterránea familiar (FMF) resistentes o intolerantes a la colchicina. Sin embargo, se desconoce si los pacientes con función renal deteriorada o preservada responden de forma diferente a los tratamientos de bloqueo de la IL-1 en cuanto a la reducción de la proteinuria y la progresión de la disfunción renal, que era el objetivo de este estudio. Materiales y métodos: Los sujetos adultos con FMF y amiloidosis demostrada por biopsia que tenían una excreción de proteínas en orina de 24 h > 150 mg/día antes de iniciar el tratamiento con canakinumab, se dividieron en dos grupos: pacientes con función renal preservada (TFG ≥ 60 mL/min) y pacientes con función renal deteriorada (TFG < 60 mL/min). En este estudio transversal se comparan la respuesta en la proteinuria y las funciones renales entre dos grupos. Resultados: En este estudio se incluyeron 18 pacientes (11 con función renal preservada y siete con función renal deteriorada). Aunque los niveles de proteinuria de ambos grupos fueron similares al inicio y a los seis meses de iniciar el tratamiento con canakinumab, la proteinuria a los 12 meses fue significativamente menor en los pacientes con función renal preservada, en comparación con los pacientes con función renal deteriorada (2.462 ± 1.760 mg/día vs. 7.065 ± 3.035 mg/día, respectivamente, p = 0,02). Todos los pacientes con función renal preservada presentaron una disminución de la proteinuria superior al 50% a los 12 meses, en comparación con los valores iniciales, mientras que ninguno de los pacientes con función renal deteriorada presentó una disminución de la proteinuria de más del 50%. (AU)

Utilidad del bloqueo de interleucina 1 con anakinra en el síndrome pospericardiotomía refractario / Usefulness of interleukin 1 receptor antagonist (anakinra) in refractory post-pericardiotomy syndrome

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High expression level of interleukin-1β is correlated with poor prognosis and PD-1 expression in patients with lung adenocarcinoma

Purpose Cytokines are vital pro-inflammatory factors and involved in tumor immune infiltration, and immune infiltration is closely related to PD-1/PD-L1 blockades immunotherapy. This study aims to explore the associations between cytokines and prognosis and also PD-1/PD-L1 expression in early lung adenocarcinoma, which is seldom reported. Methods 324 early lung adenocarcinoma patients with prior surgical resection were included and the associations between overall survival time and clinical factors and also cytokines including IL-1β, IL-6 and TNF-α were analyzed by multivariate cox regression and Kaplan–Meier curve (log-rank test). Resected tumor samples were randomly obtained to detect the PD-1/PD-L1 expression by immunohistochemistry, and Chi square test was used for relations between cytokines and PD-1/PD-L1 expression. Results In this study group, 26.2% patients showed a high level of IL-1β and patients with high IL-1β level showed 19 months shortened mOS than those with normal IL-1 β expression (mOS: 24.00, 95%CI 11.98–36.02 vs 43.00, 95% CI 37.37–48.63, p = 0.017). Among detected samples, the positive rate of PD-1 was 25.0% (13/52), and the positive rate of PD-L1 was 37.3% (19/52). The positive rate of PD-1 was 36.1% higher in high-IL-1 β-level group as compared to normal-IL-1β-level group (50.0% vs 13.9%, p = 0.012). No significant association was found between IL-1 β and PD-L1 expression. Conclusion High expression level of IL-1β was correlated with poor prognosis and higher positive rate of PD-1 expression, which gave us insights into biomarkers of survival prediction and immunotherapy in lung adenocarcinoma. Further studies were still needed (AU)

A propósito de un caso de neumonía por SARS-CoV-2 tratado con inhibidor de IL-1 / About a case of of SARS-CoV-2 pneumonia treated with IL-1 inhibitor

En la ciudad de Wuhan (provincia de Hubei, China), a finales de diciembre de 2019 se notificaron los primeros casos de una infección respiratoria causada que posteriormente se identificó como un nuevo coronavirus (SARS-CoV-2). Este cuadro se presenta como un síndrome respiratorio leve, en la mayoría de los casos, o una enfermedad más grave, con la aparición de opacidades pulmonares, con dificultad respiratoria y necesidad de ventilación mecánica no invasiva o ingreso en Unidades de Cuidados Intensivos. Estos pacientes con una enfermedad más grave debutan con una tormenta de citoquinas y activación de monocitos/macrófagos. Esta respuesta se observa igualmente en pacientes con linfohistiocitosis hemofagocítica secundaria, infecciones virales o síndrome de activación de macrófagos, enfermedades autoinmunitarias sistémicas y autoinflamatorias. Lo cual constituye una justificación para utilizar medicamentos específicamente dirigidos a reducir la tormenta de citoquinas. En cuanto al tratamiento, la evidencia es muy limitada, no pudiéndose establecer unas recomendaciones consistentes. En este caso clínico vamos a presentar un paciente con evolución satisfactoria tras el uso de inhibidores de la interleucina 1

The first cases of a respiratory infection caused by what was later identified as a new coronavirus (SARS-CoV-2) were reported in Wuhan City, Hubei Province, China in late December 2019. This picture presents as a mild respiratory syndrome, in most cases, or a more serious disease, with the appearance of pulmonary opacities, with respiratory distress and the need for non-invasive mechanical ventilation or admission to intensive care units. These more severely ill patients debut with a cytokine storm and monocyte / macrophage activation. This response is also seen in patients with secondary hemophagocytic lymphohistiocytosis, viral infections, or macrophage activation syndrome, systemic autoimmune, and autoinflammatory diseases. This constitutes a justification for using drugs specifically aimed at reducing the cytokine storm. Regarding treatment, the evidence is very limited, and consistent recommendations cannot be established. In this clinical case, we are going to present a patient with a satisfactory evolution after the use of interleukin inhibitors 1

Anakinra, una alternativa potencial en el tratamiento de la infección respiratoria grave por SARS-CoV-2 refractaria a tocilizumab / Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab

El virus SARS-CoV-2 es un nuevo virus RNA causante de la enfermedad COVID-19, declarada como pandemia por la Organización Mundial de la Salud (OMS). Produce un cuadro de neumonía atípica que puede desembocar en un fallo multiorgánico. La desregulación del sistema inmune secundaria a la infección produce un cuadro similar al síndrome de linfohistiocitosis hemofagocítica (SLHH). Varios estudios han definido la importancia que los inhibidores de la IL-6 (tocilizumab) tienen en el tratamiento de la infección por SARS-CoV-2, sin embargo, la indicación de tratamiento con inhibidores de IL-1 (anakinra) no se encuentra establecida de forma clara. Presentamos el caso de un paciente de 51 años con neumonía bilateral secundaria a infección por SARS-CoV-2 refractaria al tratamiento antiviral y anti-IL-6 que presentó mejoría clínica y analítica tras el tratamiento con anti-IL-1 (anakinra)

SARS-CoV-2 is a new RNA virus which causes coronavirus disease 2019 (COVID-19), declared a pandemic by the World Health Organization (WHO). It triggers an atypical pneumonia that can progress to multiorgan failure. COVID-19 can cause dysregulation of the immune system, triggering an inflammatory response, and simulate haemophagocytic lymphohistiocytosis. Several studies have proposed that anti-IL-6 receptor antibodies, such as tocilizumab, play an important role in the treatment of severe acute respiratory infection associated with SARS-CoV-2. However, the role of anti-IL-1 receptor antibodies, such as anakinra, in the treatment of COVID-19 has not been established. We present a case report of a 51-year-old man diagnosed with severe respiratory infection associated with SARS-CoV-2 that was refractory to antiviral and anti-IL-6 treatment, with a favourable clinical outcome and analytical improvement after treatment with anti-IL-1 (anakinra)

Fármacos en investigación / Investigational drugs

La piedra angular del tratamiento de la enfermedad pulmonar obstructiva crónica (EPOC) es la broncodilatación, y en los últimos años se ha desarrollado un importante número de moléculas que han ido cambiando paulatinamente la práctica clínica habitual en estos pacientes. Los fármacos multivalentes con más de un mecanismo de acción broncodilatador representan el próximo paso en materia de relajación del músculo liso bronquial, pero dada la creciente evidencia sobre el estrés oxidativo y estado inflamatorio generalizado de la EPOC, existe una clara tendencia a demostrar el beneficio de formulaciones antiinflamatorias respecto a un potencial control sintomático, y secundariamente la reducción de la importante carga económica que supone el consumo de recursos sanitarios. En este capítulo se pretende dar un resumen esquemático y actualizado sobre los fármacos en investigación en EPOC en las fases previas de su desarrollo clínico

Bronchodilators are the cornerstone of Chronic obstructive pulmonary disease (COPD) treatment, and in the last years an important number of new molecules have changed gradually the clinical practice in these patients. Multivalent drugs with more than one mechanism of action represent the next step in terms of bronchial smooth muscle relaxation, although, giving the growing evidence of oxidative stress and generalized inflammation in COPD, there is a clear tendency to test the potential benefit of new anti-inflammatory drugs for symptoms control in the first place and consequently the reduction of the high economic burden of this disease. This chapter aims to give a schematical and updated review of new drugs for COPD in the preclinical phases of their clinical development

Body mass index is associated with interleukin-1, adiponectin, oxidative stress and ioduria levels in healthy adults / El índice de masa corporal está asociado con los niveles de interleucina-1, adiponectina, estrés oxidativo y yoduria en adultos sanos

Background: iodine contributes to maintain the balance of the reduced and oxidized species and is also required for thyroid hormones synthesis as triiodothyronine (T3), which regulates energy metabolism in adults. Increased body mass index (BMI) is associated with inflammatory markers, oxidative stress, and abnormalities in adipocytokines secretions that are associated with obesity and chronic disease. Objective: the aim of the study is to investigate the association between ioduria, oxidative stress, total antioxidant status, adiponectin and interleukin-1 (IL-1) with BMI in healthy adults. Methods: a cross-sectional study was performed in 114 healthy adult volunteers, aged 25-44 years, divided according to their BMI in three groups: normal weight (BMI < 25), overweight (BMI ≤ 25 to < 30), obesity (BMI ≥ 30). Adiponectin and IL-1 were measured by immune-enzymatic assays; oxidative stress, by determination of malondialdehyde (MDA); and total antioxidant status (TAS) and ioduria were measured by colorimetric assays. Statistical association was done by Spearman’s test. Results: overweight and obese subjects have higher serum levels of MDA, TAS and IL-1 vs normal weight subjects. Moreover, overweight and obese subjects have lower levels of iodine and adiponectin vs normal weight subjects. MDA was positively related only with obese subjects (r = 0.787, p = 0.008) and TAS with overweight (r = 0.398, p = 0.049) and obese subjects (r = 0.448, p = 0.030). In contrast, a reverse correlation with ioduria was found in obese subjects (r = 0.463, p = 0.001). Adiponectin was negatively related only in obese subjects (r = -0.477, p = 0.001), while, IL-1 was positively related with the increase of BMI (overweight r = 0.287, p = 0.050; and obesity r = 0.515, p = 0.006).Conclusion: alteration in IL-1, adiponectin and oxidative stress levels were found to be related to overweight and obesity; also, iodine levels decreased when BMI increased, contributing to loss of redox equilibrium. All this data may play an important role in etiopathogenesis of chronic disease related to the increase of BMI

Antecedentes: el yodo contribuye a mantener el balance de especies reducidas y oxidadas y también es requerido para la síntesis de hormonas tiroideas como la triyodotironina (T3), que regula el metabolismo energético en el adulto. El incremento en el índice de masa corporal esta asociado con marcadores inflamatorios, estrés oxidativo y anormalidades en la secreción de adipocitocinas que están asociadas con la obesidad y enfermedades crónicas degenerativas. Objetivo: el objetivo del estudio es investigar la asociación entre yodaría, estrés oxidativo, estado antioxidante total, adiponectina, e interleucina 1, con el IMC en adultos saludables. Métodos: se realizo un estudio transversal con 114 adultos, 33 hombres y 81 mujeres, de entre 25 y 44 años, a los cuales se les midieron sus características clínicas, antropométricas y parámetros sociodemográficos. Los niveles de adiponectina e interleucina 1 se midieron por inmunoensayo; el estrés oxidativo, el estado antioxidante total y la yodaría, por métodos colorimétricos. Resultados: los sujetos con sobrepeso y obesidad tienen altos niveles de MDA, FRAP e IL-1 vs. los sujetos con peso normal. Sin embargo, los sujetos con sobrepeso y obesidad tienen bajos niveles de yodo y adiponectina vs. los sujetos con normopeso. El estrés oxidativo (MDA) se relacionó positivamente solo en sujetos obesos (r = 0,787, p = 0,008) y el estado antioxidante (FRAP) con sobrepeso (r = 0,398, p = 0,049) y obesidad (r = 0,448, p = 0,030). En contraste, se encontró una asociación entre yoduria y sujetos obesos (r = 0,463, r = 0,001). Los niveles de adiponectina se relacionaron negativamente solo en sujetos obesos (r = -0,477, p = 0,001), mientras que la IL-1 fue positivamente relacionada con el incremento de BMI (sobrepeso r = 0,287, p = 0,050; y obesidad r = 0,515, p = 0,006). Conclusión: La alteración en los niveles de interleucina-1, adiponectina y estrés oxidativo se relacionaron en sujetos con sobrepeso y obesidad; además, los niveles de yodo disminuyeron con el incremento del IMC, contribuyendo a la pérdida del equilibrio redox. Estos datos juegan un papel importante en la etiopatogenesis relacionada con enfermedades crónicas relacionadas con el incremento del IMC

Pericarditis aguda recurrente idiopática: presentación de un caso con respuesta favorable a anakinra / Idiopathic relapsing acute pericarditis: Report of one case with favorable response to anakinra

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Exantema urticarial refractario: síndrome de Schnitzler / Refractory urticaria: Schnitzler síndrome

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Efficacy of treatment with IL-1RA in Majeed syndrome

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Association of interleukin-1 family gene polymorphisms with juvenile idiopathic arthritis in Iranian population

BACKGROUND: Cytokines, including interleukin-1 (IL-1), seem to contribute towards the pathogenesis of juvenile idiopathic arthritis (JIA), so this study was designed to evaluate the associations of IL-1 gene cluster and IL-1 receptor (IL-1R) gene single nucleotide polymorphisms (SNPs) with JIA proneness in Iranian population. MATERIALS AND METHODS: Genomic DNA of 55 Iranian patients with JIA and 140 controls were extracted and typed for IL-1alpha gene at position −889, IL-1beta gene at positions −511 and +3962, IL-1R gene at position Pst-I 1970, and interleikin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100, using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls. RESULTS: The CC genotype of IL-1Ra at Mspa-I 11100 position was found to be more frequent in patients with JIA compared to healthy individuals (P=0.03), although the CT genotype at the same position was significantly higher in the control group in comparison with patients with JIA (P=0.02). No significant differences were observed between the two groups of case and control for IL-1alpha (−889 C/T), IL-1beta (−511 C/T and +3962 C/T) and IL-1R (Pst-1 1970 C/T). CONCLUSION: The results of the present investigation suggest that certain IL-1Ra gene variants are associated with individuals' susceptibility to JIA. Nevertheless, further studies are required to establish the results of the current study

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Amelioration of some immunological disorders caused by the faeces of the dominant true house dust mites in El-Minia Governorate, Egypt

BACKGROUND: House dust mites (HDMs) faeces are the main factor involved in respiratory disorder. The true HDMs,Dermatophagoides pteronyssinus and D. farinae, detected in the samples collected from the house dust are the most important causes of allergic disorders such as asthma. OBJECTIVE: The aim of this investigation was to study the curcuma and karkade amelioration of the allergenic immunological disorder, especially some cytokines, IgE and ROS, caused by the faeces of the dominant true HDM, D. pteronyssinus and D. farinae in valley and desert houses in EL-Minia Governorate, respectively. METHODS: HDM cultures, faeces isolation, plant extraction and ELISA techniques were used. Male albino rats were classified into control, inhaled, and treated groups. RESULTS: The present immunological study on the dominant allergenic true HDMs, D. pteronyssinus and D. farinae, revealed that significantly higher serum levels of TNF-α, IL-1β, IL-4, IL-13 and IgE were found in rats treated with both D. pteronyssinus and D. farinae faeces than the other groups. In addition, statistical analysis of ROS data showed significant difference between the curcuma- and karkade-treated groups and either the control or the faeces-treated groups (P < 0.05). CONCLUSIONS: Some immunological disturbances caused by repeated exposure to the faeces of two dominant allergenic true HDM species (D. pteronyssinus and D. farinae) in the valley and desert houses could be ameliorated by curcuma and karkade

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Clinical significance of interleukin-1 genotype in smoking patients as a predictor of peri-implantitis: a case-control study

BACKGROUND: Interleukin-1 (IL-1) is a proinflammatory cytokine that plays an important role in the pathogenesis of periodontitis, and so it might be useful to detect high-risk cases of peri-implantitis. It has been reported that IL-1 polymorphisms and smoking habit have a synergic effect, increasing the incidence of peri-implantitis. The aim of the present study was to evaluate the relationship between IL-1 gene polymorphisms and peri-implantitis in smoking patients. MATERIAL AND METHODS: A case-control study was performed in 27 patients with peri-implantitis and 27 patients with healthy implants. All patients included were smokers. IL-1A-C889T, IL-1B+C3953T and IL-1RN+T2018C were identified by polymerase chain reaction (PCR) amplification in order to establish a relation between these variables and the presence of peri-implantitis. A bivariate analysis was performed and odds-ratio (OR) were calculated. RESULTS: The incidence of peri-implantitis was significantly higher in patients with previous history of periodontitis (p = 0.024; OR=10.9). Both groups were similar regarding IL-1A-C889T, IL-1B+C3953T and IL-1RN+T2018C genotypes. No increased risk in heavy smokers with IL-1 polymorphism was found. CONCLUSIONS: IL-1 genotypes do not seem to be good predictors of peri-implantitis in the great majority of smoking patients. Furthermore, no synergic effect was found between IL-1 genotypes and heavy smokers. Patients with a previous history of periodontitis were more prone to peri-implantitis

Association of single nucleotide polymorphisms of interleukin-1 family with atopic dermatitis

BACKGROUND: Interleukin-1 (IL-1) seems to have an important role in early reactions towards microbes, while its genetic variability could affect this role in atopic patients who have a distressed immunity towards dermatological infections. METHODS: Eighty-nine patients with atopic dermatitis (AD), who were referred to a main referral paediatric hospital, were enrolled in this study. Single nucleotide polymorphisms (SNP) of the following IL-1 cluster genes were assessed in this group of patients: IL-1α −889, IL-1β −511, IL-1β +3962, IL-1R Pst-I 1970, and IL-1RA Mspa-I 11100. The results were compared with a group of 140 healthy subjects from the same region. RESULTS: Fourteen percent of the controls had TT homozygous genotype in IL-1R at position Pst-I 1970, while only 2% of the patients with AD had this genotype (p = 0.005, OR: 0.14, 95%CI: 0.02-0.64). The CC homozygous genotype was the most common genotype in IL-1α position −889 and IL-1β at position +3962 in both groups of patients with AD and the controls, while the TC heterozygous genotype was the most common genotype in IL-1β at position −511 and IL-1R at position Pst-I 1970, with no significant difference between the two groups. CONCLUSIONS: This study showed a significant negative association in the IL-1R Mspa-I 11100 TT homozygous genotype in the patients with AD

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Single-Nucleotide Polymorphisms of TNFA and IL1 in Allergic Rhinitis

Background: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. Methods: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). Results: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. Conclusions: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity (AU)

Antecedentes: La rinitis alérgica es una alteración poligénica compleja de las vías respiratorias. El TNF y la familia de la IL-1, como citoquinas proinflamatorias, parecen jugar un papel en el desarrollo de la rinitis alérgica. En este estudio de casos y controles, se evalúan las posibles asociaciones de diferentes polimorfismos de nucleótidos simples (SNPs) de los genes que regulan TNF- α e IL1. Métodos: Se estudiaron 19 pacientes con rinitis alérgica, los cuales fueron genotipados mediante PCR para primeras especie-específicos, para dos variantes del promotor del TNF- α (rs1800629 y rs361525), uno en el receptor de IL1 (rs2234650), dos SNPs en el gen de IL1ß (rs16944 y rs1143634), uno en el receptor de IL1 receptor (rs2234650) y IL1RA (rs315952). Resultados: En cuanto a los resultados obtenidos, los pacientes homicigotos para el alelo T de rs16944 en IL1ß mostraron un riesgo 8.1 veces mayor de tener rinitis alérgica que los que presentaban el alelo C. Con respecto al TNF- α, se observó una relación significativa entre los dos SNPs rs1800629 y rs361525 con la presentación de una rinitis alérgica. Excepto rs1800587, en IL1 α, y rs315952 en IL1RA, encuentran una diferencia significativa entre el grupo control y el de pacientes para el resto de los SNPs. Algunos SNPs se asociaron con el curso y con la gravedad de la enfermedad. Conclusiones: En conclusión, encontramos variantes genéticas de TNF-α y IL1 que se asocian con el riesgo de desarrollar una rinitis alérgica, y que también afectan al curso y gravedad de la enfermedad (AU)

Polymorphisms of the IL12B, IL1B, and TNFA Genes and Susceptibility to Asthma

Background: Asthma is one of the most common chronic inflammatory diseases in developed countries. Susceptibility to asthma is associated with interaction between multiple genes and environmental factors. Several cytokines play a major role in the pathophysiology of the disease. Objective: We analyzed the distribution of cytokine gene polymorphisms in a group of patients with asthma and a control group in order to determine the effect of these variants, or their combinations, on the development of clinical phenotypes. Methods: We genotyped 22 single-nucleotide polymorphisms (SNPs) corresponding to 13 cytokine genes (IFNG, IL1A, IL1B, IL1R1, IL1RN, IL2, IL4, IL4R, IL6, IL10, IL12B, TGFB1, and TNFA) in 376 individuals (219 asthmatic patients and 157 controls). Genetic association was evaluated using genotype and allele models for different asthma phenotypes. Gene–gene interactions were explored using multifactor dimensionality reduction. Results: Genotype AC of IL12B -1188 was associated with the presence of asthma. A significant association was detected between 2 SNPs analyzed in TNFA (–308 and –238) and atopic asthma and severe-persistent asthma. The IL1B TT haplotype (3962T and –511T) was also associated with atopy and moderate-persistent asthma. Conclusion: Our data show that the presence of SNPs in IL12B, TNFA, and IL1B was significantly associated with asthma, atopy, and severity of asthma. We also highlight the importance of genetic context, haplotype, and gene–gene interaction analysis in genetic association studies (AU)

Introducción: El asma es una de las enfermedades inflamatorias crónicas más frecuentes en los países desarrollados. La susceptibilidad al asma viene determinada por la interacción entre múltiples genes y factores ambientales. En la fisiopatología de esta enfermedad las citocinas desempeñan un papel importante. Objetivo: El objetivo de este estudio fue analizar la distribución de varios polimorfismos en genes de citocinas en un grupo de pacientes con asma y en un grupo control para determinar la influencia que estas variantes, o sus combinaciones génicas, desempeñan en los fenotipos clínicos. Métodos: Se analizaron 22 SNP correspondientes a 13 genes codificantes de citocinas (IFNG, IL1A, IL1B, IL1R1, IL1RN, IL2, IL4, IL4R, IL6, IL10, IL12B, TGFB1, y TNFA) en 376 individuos, 219 sujetos asmáticos y 157 controles. Las asociaciones genéticas fueron evaluadas empleando modelos genotípicos y alélicos para los distintos fenotipos de asma. Las interacciones gen-gen se analizaron mediante la plataforma Multifactor Dimensionality Reduction Platform (MDR). Resultados: El genotipo AC de IL12B -1188 se asoció con la presencia de asma. Dos SNP analizados en el gen TNFA (TNFA-308, and TNFA-238) mostraron una asociación significativa con el asma atópica y con la presencia de asma persistente grave. El haplotipo TT de IL1B (3962T y -511T) también se asoció con la presencia de atopia y con asma persistente moderada. Conclusiones: Nuestros datos muestran que la presencia de estos SNP en los genes IL12B, TNFA y IL1B se asocian significativamente con el asma, la atopia y con la gravedad del asma. También recalcamos la importancia del contexto génico, haplotipos e interacciones gen-gen en los estudios de asociación génica (AU)

Polimorfismos de la interleukina 1 (IL-1) en la Periodontitis: Revisión de la literatura / Interleukin 1 (IL-1) polymorfims in periOdontitis: rewiew of the literature

Introducción El objetivo principal de la revisión fue determinar la asociación entre los polimorfismos de la interleukina 1 (IL-1) y la posible repercusión de los mismos en la severidad de la enfermedad periodontal. Material y método Se realizó una búsqueda bibliográfica de revisiones sistemáticas y estudios longitudinales publicados desde 1990 hasta el año2011 sobre los porlimorfismos de la IL-1 en las bases de datos: PubMed, EMBASE y Cochrane. Resultados De los artículos revisados que tratan de establecer correlación entre los polimorfismos de la IL-1 y la enfermedad periodontal,24 fueron estudios longitudinales y 1 un estudio retrospectivo. De los 25 estudios, 9establecen relación entre diferentes variables clínicas y los polimorfismos de la IL-1.Los 16 restantes intentan relacionar la presencia de ciertos polimorfismos de la IL-1con la presencia y/o ausencia de periodontitis. Discusión Existe una relación demostrada entre los polimorfismos de la IL-1 y la severidad de la enfermedad periodontal constada en numerosos estudios por el empeoramiento de las (..) (AU)

The principal aim of the review was to determine the association between interleukin 1(IL-1) and periodontitis, and the possible repercussions of the same for the severity of periodontal disease. Material and method A bibliographic search was conducted, looking for systematic reviews and longitudinal studies published between 1990 and 2011into IL-1 polymorfisms, in the following databases: PubMed, EMBASE and Cochrane. Results Of the articles reviewed that sought to establish a correlation between IL-1polymorphisms and periodontal disease, 24were longitudinal studies and 1 was a retrospective study. Of the 25 studies, 9established a relationship between different clinical variables and the IL-1 polymorphisms. The remaining 16 sought to relate the presence of certain polymorphisms to IL-1 with the presence and/or absence of (..) (AU)