Enfermedad de Castleman, fisiopatología, avances en el diagnóstico y tratamiento / Castleman's disease, pathophysiology, advances in diagnosis and treatment

La enfermedad de Castleman (EC) engloba a un conjunto heterogéneo de procesos linfoproliferativos que comparten rasgos histológicos bien definidos. Se considera una enfermedad rara o minoritaria u su incidencia no es del todo conocida, aunque se estima en menos de uno por cada 100.000 habitantes. Tiene una distribución bimodal (30-40 años y luego los 60-80 años). Su incidencia es similar en ambos sexos, aunque la variante unicéntrica parece tener ligero predominio en mujeres con proporción 2:1. La EC se clasifica en una forma hialinovascular (siendo esta la más frecuente) y otra plasmocelular, relacionadas con el virus de la inmunodeficiencia humana (VIH) y el virus herpes humano tipo 8 (VHH-8), que junto a otros mecanismos autoinmunitarios desarrollan la hiperproducción de interleucina-6 (IL-6) por parte de los linfocitos B. Existen diferentes líneas de tratamiento, donde destaca el uso de anti IL-6, siendo el siltuximab el más utilizado y catalogado como el fármaco huérfano de esta patología.(AU)

Castleman's disease (CD) encompasses a heterogeneous set of reactive lymphoproliferative processes that share well-defined histologic features. CD is considered a rare or minority disease. The incidence of CD is not fully known, although it is estimated at less than 1 per 100,000 inhabitants. It has a bimodal distribution (30–40 years and then 60–80 years). The incidence is similar in both sexes, although the unicentric variant seems to have a slight predominance in women with a 2:1 ratio. CD is classified into a hyalinovascular form (this being the most frequent) and a plasmocellular form, related to the HIV and VHH-8 viruses, which together with other autoimmune mechanisms develop hyperproduction of interleukin-6 (IL-6) by B lymphocytes. There are different lines of treatment, where the use of anti IL-6 stands out, being siltuximab the most used as orphan drug in this pathology.(AU)

Castleman's disease review, pathophysiology, advances in diagnosis and treatment. / Revisión de enfermedad de Castleman, fisiopatología, avances en el diagnóstico y tratamiento.

Castleman's disease (CD) encompasses a heterogeneous set of reactive lymphoproliferative processes that share well-defined histologic features. CD is considered a rare or minority disease. The incidence of CD is not fully known, although it is estimated at less than 1 per 100,000 inhabitants. It has a bimodal distribution (30-40 years and then 60-80 years). The incidence is similar in both sexes, although the unicentric variant seems to have a slight predominance in women with a 2:1 ratio. CD is classified into a hyalinovascular form (this being the most frequent) and a plasmocellular form, related to the HIV and VHH-8 viruses, which together with other autoimmune mechanisms develop hyperproduction of interleukin-6 (IL-6) by B lymphocytes. There are different lines of treatment, where the use of anti IL-6 stands out, being siltuximab the most used as orphan drug in this pathology.

Expert consensus on the integrated diagnosis of idiopathic multicentric Castleman disease / Consenso de expertos sobre el diagnóstico integrado de la enfermedad de Castleman idiopática multicéntrica

Idiopathic multicentric Castleman disease (iMCD) is rare. The differential diagnosis includes inflammatory, autoimmune and neoplastic disease. The identification of the histopathological features of Castleman disease in the lymph node is the main diagnostic criterion.Fifty-three experts from three medical societies (SEMI, SEHH and SEAP) have created a multi-disciplinary consensus document in order to standardise the diagnosis of Castleman disease. Using the Delphi method, specific recommendations for the initial clinical, laboratory and imaging studies have been made for an integrated diagnosis of iMCD as well as for the best way to obtain samples for histopathological confirmation, correct laboratory procedure and interpretation and reporting of results.(AU)

La enfermedad de Castleman multicéntrica idiopática (ECMi) es una patología infrecuente. El diagnóstico diferencial incluye patología inflamatoria, autoinmune y neoplásica. El estudio anatomopatológico del ganglio linfático y la identificación de las características histopatológicas de la enfermedad de Castleman constituyen un criterio principal para el diagnóstico.Con el objetivo de estandarizar el proceso diagnóstico de esta patología, se ha desarrollado un documento de consenso multidisciplinario con la participación de 53 expertos de tres sociedades médicas (Sociedad Española de Medicina Interna [SEMI], Sociedad Española de Hematología y Hemoterapia [SEHH] y Sociedad Española de Anatomía Patológica [SEAP]). Mediante el método Delphi se han validado las recomendaciones específicas para el diagnóstico integrado de la ECMi con respecto a los estudios clínicos, de laboratorio y de imagen necesarios en el abordaje inicial del paciente y las recomendaciones acerca de la mejor obtención de muestras para confirmación histopatológica, así como procedimientos de laboratorio para el estudio de las muestras, interpretación de resultados y emisión de un informe anatomopatológico.(AU)

Expert consensus on the integrated diagnosis of idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is rare. The differential diagnosis includes inflammatory, autoimmune and neoplastic disease. The identification of the histopathological features of Castleman disease in the lymph node is the main diagnostic criterion. Fifty-three experts from three medical societies (SEMI, SEHH and SEAP) have created a multi-disciplinary consensus document in order to standardise the diagnosis of Castleman disease. Using the Delphi method, specific recommendations for the initial clinical, laboratory and imaging studies have been made for an integrated diagnosis of iMCD as well as for the best way to obtain samples for histopathological confirmation, correct laboratory procedure and interpretation and reporting of results.

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)

Predictive value of C-reactive protein, procalcitonin, and interleukin-6 on 30-day mortality in patients with bloodstream infections / Valor predictivo de la proteína C reactiva, procalcitonina e interleucina-6 en la mortalidad a los 30 días en pacientes con infecciones del torrente sanguíneo

Background We aimed to assess the predictive performance of C-reactive protein (hsCRP), procalcitonin (PCT), and interleukin-6 (IL-6) at different times points of bloodstream infections (BSI) management. Methods The cases were collected from January 2020 to June 2021 in the First Affiliated Hospital of Xinjiang Medical University (n=185). We collected patients’ records of hsCRP, PCT, and IL-6 serum levels and calculated the clearance of these biomarkers on day 1, day 3, and day 5 (hsCRP-1, hsCRP-3, hsCRP-5, so do PCT, and IL-6). We analyzed these predictive performances for 30-day mortality with ROC and Logistic regression. The correlation between biomarkers and their clearance rates was performed by a rank correlation method. Results The 30-day mortality was 11.35% (21/185). Serial serum hsCRP-3, IL-6-3, PCT-1, PCT-3, and PCT-5 were statistically higher in BSI mortality than survivors. Significant predictive ability was found for 30-day mortality with blood culture (BC) reported fungi (OR, 0.033; 95% CI: 0.002–0.535) and PCT-5 (OR, 1.045; 95% CI: 1.013–1.078) levels, respectively. The AUC of PCT-5 levels for 30-day mortality was 0.784 (95% CI 0.678–0.949), and the cut-off value was 5.455ng/mL. Conclusions PCT-5 is more valuable for the prognosis of 30-day mortality in patients with BSI compared to the other inflammatory biomarkers (AU)

Antecedentes Nuestro objetivo fue evaluar el rendimiento predictivo de la proteína C reactiva (hsCRP), procalcitonina (PCT) e interleucina-6 (IL-6) en distintos momentos del tratamiento de pacientes con infecciones del torrente sanguíneo. Métodos Los casos se recogieron entre enero de 2020 y junio de 2021 en el Primer Hospital Afiliado de la Universidad Médica de Xinjiang (n = 185). Los valores de los niveles séricos de hsCRP, PCT e IL-6 se obtuvieron de los registros de los pacientes y calculamos la depuración de estos biomarcadores en el día 1, el día 3 y el día 5 (hsCRP-1, hsCRP-3, hsCRP-5, PCT e IL-6). Analizamos estos rendimientos predictivos para la mortalidad a 30 días con ROC y regresión logística. La correlación entre los biomarcadores y sus tasas de eliminación se realizó mediante un método de correlación de rangos. Resultados La mortalidad a 30 días fue de 11,35% (21/185). Los valores séricos seriados de hsCRP-3, IL-6-3, PCT-1, PCT-3 y PCT-5 fueron estadísticamente más elevados en los pacientes fallecidos de infecciones del torrente sanguíneo que en los supervivientes. Se halló una capacidad predictiva significativa para la mortalidad por hongos (OR, 0,033; IC 95%: 0,002-0,535) y el valor de PCT-5 (OR, 1.045; IC 95%: 1.013-1.078), respectivamente. El AUC de los niveles de PCT-5 para la mortalidad a 30 días fue de 0,784 (IC 95%: 0,678-0,949), y el valor de corte fue de 5.455 ng/mL. Conclusiones La PCT-5 fue un parámetro de más valor para el pronóstico de mortalidad a 30 días en pacientes con infecciones del torrente sanguíneo en comparación con los demás biomarcadores inflamatorios (AU)

Predictive value of C-reactive protein, procalcitonin, and interleukin-6 on 30-day mortality in patients with bloodstream infections.

BACKGROUND: We aimed to assess the predictive performance of C-reactive protein (hsCRP), procalcitonin (PCT), and interleukin-6 (IL-6) at different times points of bloodstream infections (BSI) management. METHODS: The cases were collected from January 2020 to June 2021 in the First Affiliated Hospital of Xinjiang Medical University (n=185). We collected patients' records of hsCRP, PCT, and IL-6 serum levels and calculated the clearance of these biomarkers on day 1, day 3, and day 5 (hsCRP-1, hsCRP-3, hsCRP-5, so do PCT, and IL-6). We analyzed these predictive performances for 30-day mortality with ROC and Logistic regression. The correlation between biomarkers and their clearance rates was performed by a rank correlation method. RESULTS: The 30-day mortality was 11.35% (21/185). Serial serum hsCRP-3, IL-6-3, PCT-1, PCT-3, and PCT-5 were statistically higher in BSI mortality than survivors. Significant predictive ability was found for 30-day mortality with blood culture (BC) reported fungi (OR, 0.033; 95% CI: 0.002-0.535) and PCT-5 (OR, 1.045; 95% CI: 1.013-1.078) levels, respectively. The AUC of PCT-5 levels for 30-day mortality was 0.784 (95% CI 0.678-0.949), and the cut-off value was 5.455ng/mL. CONCLUSIONS: PCT-5 is more valuable for the prognosis of 30-day mortality in patients with BSI compared to the other inflammatory biomarkers.

Efecto del estímulo masticatorio y estrés agudo sobre la interleuquina 6, la memoria y el aprendizaje espacial en ratones Balb/c

Introducción. El estrés agudo altera la memoria y aprendizaje espacial y la expresión de la interleuquina 6 (IL-6), mientras que el estímulo masticatorio evitaría dichos efectos. Objetivo. Determinar el efecto del estímulo masticatorio y el estrés agudo sobre la expresión de interleuquina 6, la memoria y el aprendizaje espacial en ratones. Métodos. Experimento con 70 ratones albinos machos de 2 meses de edad de la cepa Balb/c que fueron distribuidos aleatoriamente en grupo A1: estrés agudo 1 hora; grupo A2: estrés agudo 1 hora + estímulo masticatorio 1 hora; grupo B1: estrés agudo 2 horas; grupo B2: estrés agudo 2 horas + estímulo masticatorio 2 horas; grupo C1: estrés agudo 3 horas; grupo C2: estrés agudo 3 horas + estímulo masticatorio 3 horas; y grupo D: sin intervención. Durante 3 días, se evaluó la memoria y el aprendizaje espacial en el laberinto acuático de Morris. La IL-6 fue determinada mediante ELISA. Resultados. La IL-6 fue mayor en el grupo B2 vs los demás grupos (p < 0,001). Además, en el primer día de evaluación, la adquisición de memoria y aprendizaje espacial fue menor en el grupo A1 vs A2 (p = 0,042). Conclusión. Solo en el primer día de evaluación encontramos que el estímulo masticatorio previno la disminución de la adquisición de memoria y aprendizaje espacial en ratones sometidos a estrés agudo de baja intensidad. Los resultados en general no fueron concluyentes sobre el efecto del estímulo masticatorio. Además, la IL-6 fue mayor en el estrés + el estímulo masticatorio (grupo B2) sobre el resto.

Introduction. Acute stress alters memory and spatial learning and the expression of interleukin 6, the chewing stimulus would prevent these effects. Objective. To determine the effect of chewing stimulation and acute stress on the expression of interleukin 6 and memory and spatial learning in mice. Methods. Experiment where 70 male albino mice of the Balb/c of age 2 month were randomly distributed into: Group A1: acute stress 1 hour; Group A2: acute stress 1 hour + chewing stimulus 1 hour; Group B1: acute stress 2 hours; Group B2: acute stress 2 hours + chewing stimulus 2 hours; Group C1: acute stress 3 hours; C2: acute stress 3 hours + chewing stimulus 3 hours; Group D: without intervention. For 3 days, spatial memory and learning were tested in the Morris water maze. Interleukin 6 (IL-6) was analyzed by ELISA test. Results. IL-6 was higher in the B2 group vs the other groups (p<0.0001). In addition, on the first day of evaluation, the acquisition of spatial memory and spatial was lower in the A1 vs. A2 group (p=0.042). Conclusión. Only on the first day of evaluation, we found that the masticatory stimulus prevented the decrease in memory acquisition and spatial learning in mice subjected to low-intensity acute stress. The results were generally inconclusive on the effect of masticatory stimulation. In addition, IL-6 was higher in the stress + masticatory stimulus (group B2) over the rest.

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.

Risk factors for medication-related osteonecrosis of the jaw and salivary IL-6 IN cancer patients / Fatores de risco para osteonecrose dos maxilares relacionada à medicação e níveis salivares de IL-6 em pacientes com câncer

Abstract Introduction Medication-related osteonecrosis of the jaws is a severe complication of the use of antiresorptive and antiangiogenic therapy, with limited treatment options and great impact on patient's quality pf life. Objective The aim of this study was to assess the risk factors associated with medication-related osteonecrosis of the jaws in oncologic patients undergoing bisphosphonate treatment. In addition, salivary levels of interleukin-6, IL-6, were measured to investigate their association with severity and risk of medication-related osteonecrosis of the jaws. Methods Case-control study with 74 patients with bone metastases from solid tumors and multiple myeloma was included. Patients were divided into three groups: 1) those undergoing bisphosphonate treatment with medication-related osteonecrosis of the jaws; 2) those undergoing bisphosphonate without medication-related osteonecrosis of the jaws; and 3) those with bisphosphonate pretreatment. The demographic and medical data of the patients were collected to assess risk. The clinical evaluation was performed to diagnose medication-related osteonecrosis of the jaws and unstimulated saliva was collected for quantification of IL-6. Results As result, it was observed that patients diagnosed with medication-related osteonecrosis of the jaws were submitted to higher number of bisphosphonate doses (p= 0.001) and monthly infusion protocol (p= 0.044; OR = 7.75). Patients who did not have routine followup with specialized dentists during therapy with bisphosphonate and smoking were associated with medication-related osteonecrosis of the jaws (p= 0.019; OR = 8.25 and p= 0.031; OR = 9.37 respectively). Group 1 had a higher frequency of treatment with chemotherapy and corticosteroids concomitant with bisphosphonate, and surgical dental procedures (p= 0.129). Salivary IL-6 levels showed no statistically significant difference between the groups (p= 0.571) or association with medication-related osteonecrosis of the jaws severity (p= 0.923). Conclusion A higher number of bisphosphonate cycles, monthly infusion protocol, no dental follow-up for oral health maintenance and smoking were associated with medication-related osteonecrosis of the jaws. Specialized dental follow up during bisphosphonate treatment has been shown to be an important factor in preventing this complication.

Resumo Introdução A osteonecrose dos maxilares relacionada à medicação é uma complicação grave da terapia antirreabsortiva e antiangiogênica, com opção de tratamento limitada e grande impacto na qualidade de vida do paciente. Objetivo Avaliar os fatores de risco associados à osteonecrose dos maxilares relacionada à medicação em pacientes oncológicos em tratamento com bifosfonato Além disso, os níveis salivares de interleucina-6 (IL-6) foram medidos para investigar sua associação com a gravidade e o risco de osteonecrose dos maxilares relacionada à medicação. Método Estudo caso-controle com 74 pacientes com metástases ósseas de tumores sólidos e mieloma múltiplo. Os pacientes foram divididos em três grupos: 1) em tratamento por bifosfonato com osteonecrose dos maxilares relacionada à medicação; 2) submetidos ao bifosfonato sem osteonecrose dos maxilares relacionada à medicação; e 3) pré-tratamento de bifosfonato. Os dados demográficos e médicos dos pacientes foram coletados para avaliar o risco. A avaliação clínica foi feita para diagnosticar osteonecrose dos maxilares relacionada à medicação e a saliva não estimulada foi coletada para quantificação da IL-6. Resultados Observou-se que os pacientes diagnosticados com osteonecrose dos maxilares relacionada à medicação foram submetidos a maior número de doses de bifosfonato (p = 0,001) e protocolo de infusão mensal (p = 0,044; OR = 7,75). Pacientes que não tiveram acompanhamento de rotina com dentistas especializados durante a terapia com bifosfonato e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação (p = 0,019; OR = 8,25 e p = 0,031; OR = 9,37, respectivamente). O grupo 1 apresentou maior frequência de tratamento com quimioterapia e corticosteroides concomitantes ao bifosfonato e procedimentos odontológicos cirúrgicos (p = 0,129). Os níveis salivares de IL-6 não apresentaram diferença estatisticamente significante entre os grupos (p = 0,571) ou associação com a gravidade do osteonecrose dos maxilares relacionada à medicação (p = 0,923). Conclusão Maior número de ciclos de bifosfonato, protocolo de infusão mensal, ausência de acompanhamento odontológico para manutenção da saúde bucal e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação. O acompanhamento odontológico especializado durante o tratamento demonstrou ser importante na prevenção dessa complicação.

Blockade of interleukin-6 as a possible therapeutic target for AA amyloidosis.

INTRODUCTION: AA (secondary) amyloidosis is a severe complication of chronic inflammatory disorders. It is characterized by the systemic deposition of an abnormal protein called amyloid, affecting mainly renal function. IL-6 is a cytokine with a relevant role in this disease development. Interleukin-receptor antagonists, like Tocilizumab (TCZ), have become possible treatment choice for AA amyloidosis. In published reports, TCZ has shown good efficacy for AA amyloidosis, being associated with regression of renal amyloid deposits. METHODS: Retrospective review that included patients with histological diagnosis of AA renal amyloidosis under treatment with TCZ during the years 2018-2019 in our center. We have registered clinical and demographic variables. Renal function was measured by means of CKD-EPI equation to estimate the glomerular filtration rate (FG) and protein/creatinine ratio (IPC) at 3, 6 and 12 months. We define renal response as a decrease by at least 30% of proteinuria and/or stabilization or improvement of FG. We consider that an anti-inflammatory response is a decrease of more than 50% in serum amyloid protein (PSA) and/or C-reactive protein (CRP). RESULTS: We collected 3 cases of patients with histologically proven AA amyloidosis treated with TCZ (2 men; 1 woman; aged 55, 74 and 75 years). The follow-up was 13, 14 and 75 months. FG was stabilized in two patients. The third patient remained on hemodialysis during follow-up, although with excellent control of her underlying inflammatory disease. In all three cases, reduced PSA and CRP were observed. There have been no adverse events. CONCLUSIONS: The TCZ may be an effective and safe option in treatment of AA amyloidosis with renal involvement. Our results position it as an interesting therapeutic option to consider in these cases, although prospective studies would be necessary to evaluate the global role of TCZ in AA amyloidosis.

El polimorfismo de un solo nucleótido rs1800795 en el gen IL6 no está asociado con el glaucoma primario de ángulo abierto en la población mexicana / The rs1800795 single nucleotide polymorphism in the IL6 gene is not associated with primary open angle glaucoma in Mexican population

Objetivo La interleucina 6 (IL-6) es una citoquina proinflamatoria con efectos pleiotrópicos que se ha relacionado con el glaucoma primario de ángulo abierto (GPAA) debido a su efecto particular de protección de las células ganglionares de la retina (CGR) contra la apoptosis. Se han asociado diferentes polimorfismos de un solo nucleótido (PSN) con el GPAA. El objetivo de este estudio fue determinar si existe una asociación entre el PSN de IL-6 rs1800795 (−174 G>C) y un mayor riesgo de padecer GPAA en la población mexicana occidental. Métodos Se incluyeron 165 pacientes mestizos mexicanos no emparentados con GPAA y 108 sujetos de control. Se extrajo el ADN genómico de los leucocitos y se purificó, seguido de la genotipificación y la amplificación por reacción en cadena de la polimerasa (PCR) con sondas TaqMan® Biosystem®. Se evaluó la diversidad alélica y genotípica entre los casos y los sujetos de control. Resultados No hubo asociación estadísticamente significativa entre las frecuencias alélicas y genotípicas, ni con modelos de asociación genética dominante ni recesiva (p>0,05). Conclusiones Aunque existe un papel de la IL6 en la fisiopatología del GPAA, nuestros resultados descartan la asociación entre la IL-6 y el PSN rs1800795 mostrando no ser un índice de mayor riesgo de GPAA en la población mexicana (AU)

Purpose Interleukin-6 (IL-6) is a proinflammatory cytokine with pleiotropic effects which has been related to primary open angle glaucoma (POAG) due to its particular effect of protecting the retinal ganglion cells (RGc) from the apoptosis. Different single nucleotide polymorphisms (SNP) have been associated with POAG. The aim of this study was to determine whether an association between IL-6 rs1800795 (−174 G>C) SNP and a higher risk for POAG is present in western Mexican population. Methods One hundred and sixty-five unrelated Mexican mestizo patients with POAG and 108 control subjects were included. Genomic DNA was extracted from leukocytes and purified, followed by genotyping and amplification by polymerase chain reaction (PCR) with Taqman Biosystem probes. Allelic and genotypic diversity was evaluated between cases and control subjects. Results There was no statistically significant association between allele and genotype frequencies, neither with dominant nor recessive genetic association models (P>.05). Conclusion Even though there is a role of IL6 in the pathophysiology of POAG, our results ruled out the association between IL-6 and the rs1800795 SNP showing not to be an index of higher risk for POAG in Mexican population (AU)

The rs1800795 single nucleotide polymorphism in the IL6 gene is not associated with primary open angle glaucoma in Mexican population.

PURPOSE: Interleukin-6 (IL-6) is a proinflammatory cytokine with pleiotropic effects which has been related to primary open angle glaucoma (POAG) due to its particular effect of protecting the retinal ganglion cells (RGc) from the apoptosis. Different single nucleotide polymorphisms (SNP) have been associated with POAG. The aim of this study was to determine whether an association between IL-6 rs1800795 (-174 G>C) SNP and a higher risk for POAG is present in western Mexican population. METHODS: One hundred and sixty-five unrelated Mexican mestizo patients with POAG and 108 control subjects were included. Genomic DNA was extracted from leukocytes and purified, followed by genotyping and amplification by polymerase chain reaction (PCR) with Taqman Biosystem probes. Allelic and genotypic diversity was evaluated between cases and control subjects. RESULTS: There was no statistically significant association between allele and genotype frequencies, neither with dominant nor recessive genetic association models (p > 0.05). CONCLUSION: Even though there is a role of IL6 in the pathophysiology of POAG, our results ruled out the association between IL-6 and the rs1800795 SNP showing not to be an index of higher risk for POAG in Mexican population.

Revisión sistemática y metaanálisis de inhibidores de interleucina-6 para reducir la mortalidad en pacientes hospitalizados con COVID-19 / Systematic review and meta-analysis of interleulin-6 inhibitors in reducing mortality for hospitalized patients with COVID-19

Objetivo: Un año después de la declaración de la pandemia porSARS‑CoV-2, solo dexametasona había mostrado claramente una reducciónde la mortalidad en pacientes hospitalizados por COVID-19. Losresultados de los inhibidores de interleucina 6 son diversos y poco claros.El objetivo de este trabajo es revisar y analizar el efecto de tocilizumaby sarilumab sobre la supervivencia de los pacientes en este escenario.Método: La revisión sistemática siguió las recomendaciones de PRISMA.Se realizó una búsqueda sistemática en Medline, Embase y medRxiv paraidentificar ensayos controlados aleatorizados con tocilizumab o sarilumaben pacientes hospitalizados con COVID-19. Se recopilaron los datosde mortalidad de pacientes críticos y no críticos y se llevó a cabo unmetaanálisis de efectos aleatorios (Der Simonian-Laird) para ambos subgruposy para toda la población, usando el software MAVIS v. 1.1.3. Lasimilitud y homogeneidad entre los ensayos fue evaluada.Resultados: Se identificaron 25 y 23 artículos en Medline y Embase,respectivamente; cinco eran ensayos con tocilizumab y/o sarilumab; seidentificaron dos más en medRxiv. En total, siete ensayos clínicos aleatorizadoscumplieron los criterios de inclusión. Posteriormente, se prepublicóotro ensayo que cumplía los criterios de inclusión y se incorporó absoalanálisis. El metaanálisis, con ocho ensayos clínicos aleatorizados y6.340 pacientes, mostró un beneficio sobre la mortalidad para los inhibidoresde interleucina-6 (hazard ratio 0,85; intervalo de confianza al 95%0,74-0,99), con baja heterogeneidad (I2 = 7%), pero reducida similitudentre los estudios. Los resultados no mostraron diferencias entre pacientescríticos y no críticos. Un análisis de sensibilidad excluyendo estudios heterogéneoso no similares mostró resultados diferentes, sin beneficio y conbaja precisión del resultado en pacientes no críticos.

Objective: One year after the declaration of the SARS-CoV-2 pandemic,only dexamethasone has clearly shown a reduction in mortality forCOVID-19 hospitalized patients. For interleukin-6 inhibitors, results arevariable and unclear. The objective was to review and analyze the effectof tocilizumab and sarilumab on survival in this setting.Method: The PRISMA statements were fulfilled for the systematic review.A systematic search in Medline, Embase and medRxiv was conductedto identify randomized controlled trials with tocilizumab or sarilumab inhospitalized patients with COVID-19. Mortality data from non-critical andcritical patients were extracted. A random-effects (DerSimonian-Laird)meta-analysis was performed for both subgroups and the whole populationusing MAVIS software v. 1.1.3. Similarity and homogeneity amongtrials were assessed.Results: Twenty-five and 23 articles were identified in Medline andEmbase, respectively, five were trials with tocilizumab and/or sarilumab;two more were identified at medRxiv. Seven randomized clinical trialsfulfilled the inclusion criteria. Another trial was pre-published and includedpost-hoc. The meta-analysis, with eight randomized clinical trialsand 6,340 patients, showed a benefit on mortality for interleukin-6 inhibitor (hazard ratio 0.85; confidence interval 95% 0.74-0.99), lowheterogeneity (I2 = 7%), but a low similarity among studies. The resultsshowed no differences among critical and non-critical patients. A sensitivityanalysis excluding non-similar or heterogeneous studies showeddifferent results, without benefit and with low precision of the result innon-critical patients.

The influence of macrophage polarisation status and IL-6 in breast carcinoma invasion / La influencia del estado de polarización de los macrófagos y la IL-6 en la invasión del carcinoma de mama

Introduction: Breast cancer metastasis accounts for the majority of deaths from breast cancer. The knowledge on IL-6 affecting cancer cell metatastatic behaviour need to be studied.Objectives: This study aim to examine the association of macrophage polarisation status and IL-6 with clinicopathological criteria and lymphovascular invasion (LVI) of breast carcinoma.Material & Method: 81 cases of FFPE breast carcinoma samples were stained with IL6, CD80 (M1 macrophage), CD204 and CD163 (M2 macrophage) and CD68 (pan-macrophage marker). The macrophages count were evaluated based on 3 hotspots of positively stained cells. IL-6 scoring was done using the H-score method.Result: Significant association was observed between CD68 marker with blood vessel invasion (p-value = 0.014), lymphatic vessel invasion (p-value = 0.005), and metastasis (p-value =0.028). CD68 was also significantly associated with CD204 (p = 0.027). CD80 biomarker also showing significant association with patient tumour grade (p-value = 0.054), ER (0.028) and PR (0.010) in patient clinical data and CD204 is significantly associated with ER (0.053) and PR (0.054) patient clinical data. Meanhile, there is no significant association of IL-6 with the patient clinical data.Conclusion: There is no significant association of IL-6 with the patient clinicopathological data obtained in this study while CD68 showed significant correlation with M2 macrophage biomarker and LVI indicating the influence of M1 and M2 macrophage in breast cancer metastatic pathway through blood and lymphatic vessel invasion. (AU)

Introducción: La metástasis del cáncer de mama representa la mayoría de las muertes por cáncer de mama. Es necesario estudiar el conocimiento sobre la IL-6 que afecta el comportamiento metatastásico de las células cancerosas.Objetivos: Este estudio tiene como objetivo examinar la asociación del estado de polarización de los macrófagos y la IL-6 con los criterios clínico-patológicos y la invasión linfovascular (LVI) del carcinoma de mama.Material y método: 81 casos de muestras de carcinoma de mama FFPE se tiñeron con IL6, CD80 (macrófago M1), CD204 y CD163 (macrófago M2) y CD68 (marcador pan-macrófago). El recuento de macrófagos se evaluó en base a 3 hotspots de células teñidas positivamente. La puntuación de IL-6 se realizó mediante el método de puntuación H.Resultado: Se observó una asociación significativa entre el marcador CD68 con invasión de vasos sanguíneos (valour de p = 0,014), invasión de vasos linfáticos (valour de p = 0,005) y metástasis (valour de p = 0,028). CD68 también se asoció significativamente con CD204 (p = 0.027). El biomarcador CD80 también muestra una asociación significativa con el grado del tumour del paciente (valour p = 0,054), ER (0,028) y PR (0,010) en los datos clínicos del paciente y el CD204 se asocia significativamente con los datos clínicos del paciente ER (0,053) y PR (0,054). Mientras tanto, no existe una asociación significativa de IL-6 con los datos clínicos del paciente.Conclusión: No existe una asociación significativa de IL-6 con los datos clínico-patológicos del paciente obtenidos en este estudio, mientras que CD68 mostró una correlación significativa con el biomarcador de macrófagos M2 y LVI que indica la influencia de los macrófagos M1 y M2 en la vía metastásica del cáncer de mama a través de la invasión de vasos sanguíneos y linfáticos. (AU)

La inhibición de la interleucina-6 como posible diana terapéutica en la amiloidosis AA / Blockade of interleukin-6 as a possible therapeutic target for AA amyloidosis

Introducción: La amiloidosis secundaria (AA) es una complicación grave asociada a enfermedades inflamatorias. Se caracteriza por el depósito sistémico de proteína fibrilar AA, con especial repercusión renal. La participación de la interleucina 6 en su mecanismo patogénico ha supuesto que tocilizumab (TCZ) sea considerado una opción terapéutica en estos pacientes. Varias series publicadas muestran su eficacia en el tratamiento de la amiloidosis AA, permitiendo incluso la regresión de depósitos renales ya presentes.Material y métodoRevisión retrospectiva que incluyó pacientes con diagnóstico histológico de amiloidosis renal AA en tratamiento con TCZ durante los años 2018-2019 en nuestro centro. Registramos variables clínicas y demográficas; evaluamos la función renal mediante filtrado glomerular (FG) calculado por CKD-EPI e índice proteína/creatinina a los 3, 6 y 12 meses de seguimiento. Definimos «respuesta renal» como la disminución >30% de la proteinuria y/o estabilización o mejoría del FG. Consideramos «respuesta antiinflamatoria» la disminución >50% de las cifras de proteína sérica amiloide (PSA) y/o proteína C reactiva (PCR).ResultadosPresentamos una serie de 3 pacientes (2 varones y una mujer; 55, 74 y 75 años, respectivamente), con un tiempo de seguimiento de 13, 14 y 75 meses, respectivamente. Con la terapia con TCZ, el FG se estabilizó en 2 pacientes; el tercero permaneció en hemodiálisis durante el seguimiento, aunque con excelente control de su enfermedad inflamatoria de base; a los 12 meses recibió un trasplante renal. En los 3 casos se objetivó reducción de proteína PSA y PCR. No se han producido eventos adversos. (AU)

Introduction: AA (secondary) amyloidosis is a severe complication of chronic inflammatory disorders. It is characterized by the systemic deposition of an abnormal protein called amyloid, affecting mainly renal function. IL-6 is a cytokine with a relevant role in this disease development. Interleukin-receptor antagonists, like Tocilizumab (TCZ), have become possible treatment choice for AA amyloidosis. In published reports, TCZ has shown good efficacy for AA amyloidosis, being associated with regression of renal amyloid deposits.MethodsRetrospective review that included patients with histological diagnosis of AA renal amyloidosis under treatment with TCZ during the years 2018-2019 in our center. We have registered clinical and demographic variables. Renal function was measured by means of CKD-EPI equation to estimate the glomerular filtration rate (FG) and protein/creatinine ratio (IPC) at 3, 6 and 12 months. We define renal response as a decrease by at least 30% of proteinuria and/or stabilization or improvement of FG. We consider that an anti-inflammatory response is a decrease of more than 50% in serum amyloid protein (PSA) and/or C-reactive protein (CRP).ResultsWe collected 3 cases of patients with histologically proven AA amyloidosis treated with TCZ (2 men; 1 woman; aged 55, 74 and 75 years). The follow-up was 13, 14 and 75 months. FG was stabilized in two patients. The third patient remained on hemodialysis during follow-up, although with excellent control of her underlying inflammatory disease. In all three cases, reduced PSA and CRP were observed. There have been no adverse events.ConclusionsThe TCZ may be an effective and safe option in treatment of AA amyloidosis with renal involvement. Our results position it as an interesting therapeutic option to consider in these cases, although prospective studies would be necessary to evaluate the global role of TCZ in AA amyloidosis. (AU)

IL-6 levels are associated with clinical status in patients with Myasthenia Gravis / Os níveis de IL-6 estão associados com o status clínico de pacientes com Miastenia Gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. OBJECTIVES: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. METHODS: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. RESULTS: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. CONCLUSION: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MGC.

INTRODUÇÃO: A Miastenia Gravis (MG) é uma doença autoimune caracterizada por fraqueza muscular flutuante. OBJETIVOS: avaliar os níveis plasmáticos de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, e IL-17A) em pacientes com MG e controles e investigar se essas citocinas estão associadas com parâmetros clínicos. Este estudo foi conduzido no ambulatório de doenças neuromusculares do Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brasil. MÉTODOS: Foi coletado sangue periféricos e os níveis plasmáticos das citocinas foram medidos por citometria em 80 pacientes com MG tratados e em 50 controles. O MG composite (MGC) foi utilizado para avaliar a fraqueza muscular e a gravidade dos sintomas motores típicos da MG. RESULTADOS: Os pacientes com MG em tratamento apresentaram menores níveis de todas as citocinas avaliadas comparados ao controle. Houve uma correlação negativa entre os níveis de IL-6 e o MGC, indicando que altos níveis de IL-6 estão associados com melhor controle da doença. CONCLUSÃO: este estudo exploratório sugere que a IL-6 está associada com o status clínico da MG, quando avaliado pelo MGC.

The association between interleukin-6 promoter polymorphisms and rheumatoid arthritis by ethnicity: A meta-analysis of 33 studies.

OBJECTIVE: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. MATERIAL AND METHODS: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. RESULTS: From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28-25.14, ORhomozygous=5.84, 95%CI: 2.06-16.56, ORdominant=7.21, 95%CI: 2.30-22.63, ORrecessive=5.04, 95%CI: 1.78-14.28, ORallelic=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10-4.81, ORdominant=2.27, 95%CI: 1.22-4.22, ORallelic=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08-.82, ORrecessive=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16-2.09, ORrecessive=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed. CONCLUSIONS: Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.

The association between interleukin-6 promoter polymorphisms and rheumatoid arthritis by ethnicity: A meta-analysis of 33 studies / Asociación entre los polimorfismos del promotor de la interleucina-6 y la artritis reumatoide analizado por etnicidad: un metaanálisis de 33 estudios

Objective: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (−174 G>C, −572 G>C, and −597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. Material and methods: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. Results: From 708 identified publications, 33 were used in this analysis. For the −174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28–25.14, ORhomozygous=5.84, 95%CI: 2.06–16.56, ORdominant=7.21, 95%CI: 2.30–22.63, ORrecessive=5.04, 95%CI: 1.78–14.28, ORallelic=6.60, 95%CI: 2.26–19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10–4.81, ORdominant=2.27, 95%CI: 1.22–4.22, ORallelic=2.29, 95%CI: 1.24–4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08–.82, ORrecessive=.25, 95%CI: .08–.80, p<.05). For the −572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16–2.09, ORrecessive=1.63, 95%CI: 1.08–2.45, p<.05). For the −597 polymorphism, no association was observed. Conclusions: Here, the −174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the −572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.(AU)

Objetivos: Realizamos un meta-análisis para determinar el efecto de los polimorfismos del promotor de interleucina-6 (IL-6) (-174 G>C, -572 G>C, y -597 G>A) sobre el desarrollo de artritis reumatoide (RA) analizado por etnicidad. Materiales y métodos: En las bases de datos PubMed, EBSCO, LILACS y Scopus se buscaron estudios con la asociación entre polimorfismo de IL-6 y RA publicados hasta noviembre 2018. se obtuvieron las distribuciones de genotipo y de acuerdo al nivel de heterogeneidad el efecto fijo o aleatorio fueron utilizados para calcular los Odds Ratio (OR) con intervalos de confianza del 95% para los modelos genéticos heterocigoto, homocigoto, dominante, recesivo y alélico. Resultados: De 708 estudios identificados, 33 fueron utilizados para este análisis. Para el polimorfismo -174, los países Asiáticos (ORheterocigoto=7,57, 95%CI: 2,28–25,14, ORhomocigoto=5,84, 95%CI: 2,06-16,56, ORdominante=7,21, 95%CI: 2,30-22,63, ORrecesivo=5,04, 95%CI: 1,78-14,28, ORalélico=6,60, 95%CI: 2,26-19,28, p<0,05) y del Medio Oriente (ORheterocigoto=2,30, 95%CI: 1,10-4,81, ORdominante=2,27, 95%CI: 1,22-4,22, ORalélico=2,29, 95%CI: 1,24-4,23, p<0,05) están asociados con el riesgo de desarrollar RA significativamente. Mientras que, para los Latinos, el alelo-C está asociado con un beneficio (ORhomocigoto=0,26, 95%CI: 0,08-0,82, ORrecesivo=0,25, 95%CI: 0,08-0,80, p<0,05). Para el polimorfismo -572, los Asiáticos están asociados significativamente con los modelos genéticos homocigoto y recesivo (8 estudios, ORhomocigoto=1,56, 95%CI: 1,16-2,09, ORrecesivo=1,63, 95%CI: 1,08-2,45, p<0,05). Para el polimorfismo -597, no se observó asociación. Conclusiones: El polimorfismo -174 G>C aumenta el riesgo de desarrollar RA en población Asiática y Medio Oriente. Curiosamente, para los Latinos el polimorfismo está asociado con un beneficio. Para el polimorfismo -572, solo la población Asiática demuestra una aumento en el riesgo de desarrollar RA con el genotipo CC.(AU)

Niveles séricos de interleucina-6 en pacientes con diabetes tipo 2 y su correlación con el perfil lipídico / Serum levels of interleukin-6 in patients with type 2 diabetes and its correlation with the lipid profile

La diabetes mellitus es una enfermedad metabólica caracterizada por hiperglucemia, a consecuencia de defectos en la producción, secreción y/o acción de la insulina, produciendo alteraciones en el metabolismo de los hidratos de carbono, lípidos y proteínas; asociado a un proceso inflamatorio crónica en un plazo variable, que provocara lesiones macro y microvasculares. Objetivo: Evaluar los niveles séricos de interleucina-6 (IL-6) en pacientes diabéticos tipo 2 y su correlación con el perfil lipídico. Métodos: Se realizó estudio descriptivo analítico y transversal, comprendido por 60 adultos de ambos sexos entre 30 a 60 años, con diabetes mellitus tipo 2 que acudieron a consulta de Endocrinología del Hospital Militar Universitario Dr. Carlos Arvelo. Se les determino glucemia basal, interleucina-6, perfil lipídico, resultados relacionados con parámetros antropométricos, composición corporal, la edad y tiempo de evolución de la diabetes. Resultados: La edad promedio de 51,60 años ± 6,51, donde el 71,6% correspondieron al sexo femenino y el 28,3% al masculino, tiempo de evolución de la diabetes entre 1 mes y 37 años, con un promedio de 10,97 años. Se presentó correlación positiva baja y estadísticamente significativa entre interleucina 6 y los parámetros de triglicéridos, VLDL y no-HDL Conclusión: Se encontró valores elevados de IL-6 en todos los pacientes diabéticos tipo 2, así como una correlación positiva entre IL-6 y las lipoproteínas ricas en triglicéridos. Esto respalda la idea de que la hipertrigliceridemia puede causar cambios inflamatorios en pacientes diabéticos y esto elevaría el riesgo cardiovascular de estos pacientes(AU)