52-Week Mid-term Efficacy of Tildrakizumab in Moderate-to-severe Psoriasis: A Real-life Multicenter Experience. / [Artículo traducido] Eficacia a medio plazo (52 semanas) de tildrakizumab en el tratamiento de la psoriasis moderada a severa: un estudio multicéntrico de práctica clínica.

Tildrakizumab is an IL-23-inhibitor that has been approved to treat plaque psoriasis. However, few reports have become available on its efficacy profile in the real-world. Our objective was to study the mid-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the Spanish routine clinical practice setting. This was a retrospective multicenter study that included a total of 91 psoriatic patients on tildrakizumab. The mean Psoriasis Area and Severity Index (PASI) was 9.09 (SD, 5.30). The overall tildrakizumab survival rate was 93.47% for a mean treatment exposure of 30.18 weeks (SD, 16.57). No drug discontinuation was associated with drug tolerability, or adverse reactions. Absolute PASI ≤3 was reached by 91.3% and 96.5% of the patients on weeks 28 and 52, respectively. Response was not impacted by weight, age (>65), metabolic syndrome, presence of arthritis, or previous number of biological therapies used. Based on our own experience tildrakizumab is an effective strategy to treat plaque psoriasis and difficult-to-treat-areas.

52-Week Mid-term Efficacy of Tildrakizumab in Moderate-to-severe Psoriasis: A Real-life Multicenter Experience.

Tildrakizumab is an IL-23-inhibitor that has been approved to treat plaque psoriasis. However, few reports have become available on its efficacy profile in the real-world. Our objective was to study the mid-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the Spanish routine clinical practice setting. This was a retrospective multicenter study that included a total of 91 psoriatic patients on tildrakizumab. The mean Psoriasis Area and Severity Index (PASI) was 9.09 (SD, 5.30). The overall tildrakizumab survival rate was 93.47% for a mean treatment exposure of 30.18 weeks (SD, 16.57). No drug discontinuation was associated with drug tolerability, or adverse reactions. Absolute PASI ≤3 was reached by 91.3% and 96.5% of the patients on weeks 28 and 52, respectively. Response was not impacted by weight, age (>65), metabolic syndrome, presence of arthritis, or previous number of biological therapies used. Based on our own experience tildrakizumab is an effective strategy to treat plaque psoriasis and difficult-to-treat-areas.

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

BACKGROUND: Interleukin-1ß (IL-1ß) increases necrotic neuronal cell death in the CA1 area after induced status epilepticus (SE) in developing rats. However, it remains uncertain whether IL-1ß has a similar effect on the hippocampal dentate gyrus (DG). In this study, we analysed the effects of IL-1ß 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-1ß (at 0, 0.3, 3, 30, or 300ng/µL) in the right ventricle; another group was injected with IL-1ß receptor (IL-1R1) antagonist (IL-1Ra, at 30ng/µL) of IL-1RI antagonist (IL-1Ra) alone, and additional group with 30ng/µL of IL-1Ra plus 3ng/µL of IL-1ß. 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 300ng/µL of IL-1ß in comparison with the vehicle group. A similar effect was observed in the hippocampal DG contralateral to the site of injection of 3ng/µL of IL-1ß. Administration of both of IL-1ß and IL-1Ra failed to prevent an increase in the number of eosinophilic cells. CONCLUSION: Our data suggest that IL-1ß increases apoptotic neuronal cell death caused by SE in the hippocampal GD, which is a mechanism independent of IL-1RI activation.

Clinical Efficacy and Safety of Ixekizumab for Treatment of Psoriasis.

Psoriasis is a common, chronic, inflammatory skin disorder with a physical and emotional burden. Emerging evidence suggests that IL17-A is a key cytokine in the immunopathogenesis of psoriasis. Ixekizumab is a humanized IgG4 monoclonal antibody that acts by neutralizing IL-17A. Data from Phase I-III studies reveal that ixekizumab is highly effective in treating patients with moderate-to-severe plaque psoriasis. A large proportion of patients receiving ixekizumab achieved or maintained complete or near complete resolution of psoriatic lesions with an acceptable safety profile through week 60. These remarkable results introduce a paradigm shift in the medically management of psoriasis, where complete or almost completely clear skin becomes the new therapeutic goal.

[Castleman's disease, pathophysiology, advances in diagnosis and treatment]. / 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.

The effect of interleukin-33 expression on prognosis in patients with nasopharyngeal carcinoma.

INTRODUCTION: Interleukin-33 (IL-33) is a newly defined inflammatory cytokine that is a member of the interleukin-1 (IL-1) gene family. This cytokine is expressed in structural cells, such as the vascular endothelium, bronchial epithelial cells, keratinocytes, epithelial cells of the stomach, and fibroblastic reticular cells of lymphoid tissues. Several studies suggest that IL-33 plays a role in head-and-neck cancer. The aim of this study was to retrospectively examine IL-33 expression in nasopharyngeal carcinoma (NPC) and to evaluate its relationship between clinicopathological characteristics and prognosis. METHODS: In this monocentric, retrospective analysis, the data of 43 cases diagnosed with primary NPC and 20 cases with normal nasopharyngeal tissue (diagnosed between 2014 and 2020) were evaluated regarding the relationship between the immunohistochemically analyzed IL-33 expression status and corresponding clinicopathological parameters. RESULTS: The mean age was 56.9 years. The majority (67.4%) of the patients had an early tumor stage (T1-T2). IL-33 expression was positive in 56% of the cases. The five-year overall survival rate was 77% for all patients, 90% for the patients with positive IL-33 expression, and 55% for those without IL-33 expression (p = 0.008, univariate analysis). In multivariate analysis, IL-33 expression was shown to be the only independent prognostic marker for nasopharyngeal carcinoma (p = 0.014). CONCLUSION: This retrospective study showed that IL-33 expression could be considered an independent factor affecting positively prognosis in NPC.

Perceived quality of life in patients with psoriasis treated with interleukin 17 and 23 inhibitors. / Calidad de vida percibida por los pacientes con psoriasis tratados con inhibidores de interleucina 17 y 23.

OBJECTIVE: To determine the effectiveness in terms of quality of life perceived by adult patients with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors and to identify associated factors. METHOD: Cross-sectional observational study including adult patients diagnosed with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors for at least 12 or 16 weeks in follow-up, respectively. RESULTS: Forty-one patients were included: 65% male, median age 54 years (SD=13). The included patients were treated with ixekizumab 35%, guselkumab 25%, secukinumab 17.5%, brodalumab 15% and risankizumab 7.5%. Psoariasis area severity index (PASI) reduction was 94.6% (RIC 76.8-100%), DLQI of 1 (RIC 0-2.75), DLQI ≤ 1, 60%. The most affected health dimensions were symptoms and perceptions (57.5%), activities of daily living (27.5%) and discomfort caused with treatment (17.5%). No association was found between DLQI score < 1 and demographic, comorbidities and treatment-related variables. The median PASI reduction in patients with DLQI<1 was superior to patients with DLQI > 1 (100% vs 90.2%, p=0.025). CONCLUSIONS: Patients with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors achieve adequate therapeutic targets achieving the target set according to clinical practice guideline recommendations (score ≤1 on the DLQI questionnaire and 90-100% reduction in the PASI index) and in accordance with the results of recent meta-analyses and real-life studies. A greater reduction of the PASI index is observed in the group reaching the quality of life target, there being the possibility of using patient-reported outcomes in the evaluation of treatment effectiveness.

Perceived quality of life in patients with psoriasis treated with interleukin 17 or 23 inhibitors.

OBJECTIVE: To determine the effectiveness in terms of quality of life perceived by adult patients with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors and to identify associated factors. METHOD: Cross-sectional observational study including adult patients diagnosed with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors for at least 12 or 16 weeks in follow-up, respectively. RESULTS: Forty-one patients were included: 65% male, median age 54 years (SD=13). The included patients were treated with ixekizumab 35%, guselkumab 25%, secukinumab 17.5%, brodalumab 15%, and risankizumab 7.5%. Psoariasis area severity index (PASI) reduction was 94.6% (RIC 76.8-100%), DLQI of 1 (RIC 0-2.75), DLQI≤1 60%. The most affected health dimensions were symptoms and perceptions (57.5%), activities of daily living (27.5%), and discomfort caused with treatment (17.5%). No association was found between DLQI score <1 and demographic, comorbidities, and treatment-related variables. The median PASI reduction in patients with DLQI<1 was superior to patients with DLQI>1 (100% vs 90.2%, p=.025). CONCLUSIONS: Patients with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors achieve adequate therapeutic targets achieving the target set according to clinical practice guideline recommendations (score ≤1 on the DLQI questionnaire and 90-100% reduction in the PASI index) and in accordance with the results of recent meta-analyses and real-life studies. A greater reduction of the PASI index is observed in the group reaching the quality of life target, there being the possibility of using patient-reported outcomes in the evaluation of treatment effectiveness.

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

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

[Control de asma grave predominantemente eosinofílica con el uso de anti IL-5].

Background: Asthma is a chronic inflammatory disease of the airways, caused by inflammatory cells and mediators, associated with smooth muscle dysfunction, causing variable airflow obstruction. With high, low and mixed type 2 immunoinflammatory mechanisms (endotypes). Severe asthma is that which requires step 4 or 5 of treatment (GINA 2023). The TH2 High phenotype, non-allergic with eosinophilia and FENO, is the second most common. It affects 300 million people around the world. Objetive: Describe asthma biomarkers after the use of antiinterleukin 5, Benralizumab, in adults with severe asthma. Methods: Case report, descriptive study. Patients with severe eosinophilic asthma and chronic polyposis rhinosinusitis under treatment with anti-IL5 were included, evaluating inflammatory biomarkers. Results: Serum eosinophils, FENO, ACT, spirometry, and exacerbations were measured in 8 patients at baseline and 6 months after treatment. The FEV1-FVC was 51% with improvement up to 95% later. 5 patients had FENO > 45 ppm subsequently only 3 continued to be inflamed. Eosinophilia 150 cells and subsequently only 1 patient persisted with eosinophilia 200 cells. Initial ACT < 19 in 7 patients Final ACT >19 in 7 patients. Exacerbations 8 patients with 2 or more exacerba- tions subsequently only 1 patient presented exacerbation. Conclusion: The use of anti-interleukin 5 (benralizumab) does reduce inflammatory markers, improves control and number of exacerbations in the short term. Monoclonal antibodies (Anti IL-5), if they improve inflammatory biomarkers, if clinical characteristics and inflammatory biomarkers are taken into account, it favors adequate asthma control.

Antecedentes: El asma es una enfermedad inflamatoria crónica de vías respiratorias, provocada por células y mediadores inflamatorios, asociado a disfunción del músculo liso, provocando obstrucción variable del flujo aereo. Con mecanismos inmunoinflamatorios tipo 2 altos, bajos y mixtos (endotipos). Asma grave es aquella que requiere paso 4 o 5 de tratamiento (GINA 2023). El fenotipo TH2 Alto, no alergico con eosinofilia y FENO, es el segundo más común. Afecta a 300 millones de personas alrededor del mundo. Objetivo: Describir biomarcadores de asma, posterior al uso de antiinterleucina 5, Benralizumab, en adultos con asma grave. Métodos: Reporte de casos, estudio descriptivo. Se incluyeron pacientes con asma grave eosinofilica y rinosinusitis crónica poliposica en tratamiento con an- ti-IL5, evaluando biomarcadores inflamatorios Resultados: En 8 pacientes se midieron eosinófilos séricos, FENO, ACT, espirometría y exacerbaciones al inicio y 6 meses después del tratamiento. El FEV1-FVC fue 51% con mejoría hasta 95% después. 5 pacientes tenían FENO >45 ppm posteriormente solo 3 continuron inflamados. Eosinofilia 150 células y posterior- mente solo 1 paciente persistió con eosinofilia 200 células. ACT inicial < 19 en 7 pacientes ACT final > 19 en 7 pacientes. Exacerbaciones 8 pacientes con 2 o más exacerbaciones posteriormente solo 1 paciente presentó exacerbación. Conclusión: El uso de antiinterleucina 5 (Benralizumab) si disminuye marcadores inflamatorios, mejora el control y número de exacerbaciones a corto plazo. Los anticuerpos monoclonales (Anti IL-5), si mejoran biomarcadores inflamatorios si se toman en cuenta caracteristicas clínicas y biomarcadores inflamatorios favorece adecuado control de asma.

[Perfilamiento del paciente con asma grave eosinofílica para el tratamiento biológico con Mepolizumab y su efectividad en el control de la enfermedad].

Background: Management of severe eosinophilic asthma includes typing to identify allergic, eosinophilic and non-HT2 phenotypes. Elevated eosinophil levels are associated with higher IL-5 levels. Eosinophils during their migration to target tissues secrete proteins that damage the activated bronchial epithelium and correlate with asthma severity. Mepolizumab, a humanized monoclonal antibody that binds and neutralizes IL-5. Objectives: To describe experience with the use of biological anti interleukin 5 Mepolizumab. Methods: Case report, descriptive study. We included patients with severe uncontrolled asthma, a history of rhinosinusitis with nasal polyposis and/or EREA. Eosinophils 150 cells/µL, FeNO 25 ppb and spirometry with obstructive pattern. Results: 6 women with a diagnosis of severe asthma were included. Initial eosinophil values of 180 - 630 cél/µL, IgE 176 - 2500 Ui/ml, FENO 23 -39, ACT at 2, 4 and 6 months of use, minimum of 9 and maximum end of 25. Significant improvement in the ACT test from the first two months of use, decreased inhaled steroid and 0 to 2 exacerbations in 6 months. Conclusions: There are multiple studies, there are no statistically significant reports to demonstrate superiority with the use of a specific biological, together with the different economic limitations that exist in the country. It is necessary to identify target populations with phenotypes In Mexico there are few hospitals with these therapies, it is necessary to continue with the constant evaluation and contribution of information to find the right treatment for the Mexican population. that will respond to a specific therapy and direct treatment.

Antecedentes: El manejo del asma grave eosinofílica incluye tipificación para identificar fenotipos alérgicos, eosinofílicos y no TH2. Niveles elevados de eosi- nófilos se asocia a mayor nivel de IL-5. Los eosinófilos durante su migración a los tejidos diana, secretan proteínas que dañan el epitelio bronquial activado y se correlacionan con la gravedad del asma. Mepolizumab, anticuerpo monoclonal humanizado que se une y neutraliza la IL-5. Métodos: Describir experiencia con el uso de biológico anti-interleucina 5 Mepolizumab. Objetivos: Reporte de casos, estudio descriptivo. Se incluyeron pacientes con asma grave descontrolada, antecedente de Rinosinusitis con poliposis nasal y/o EREA. Eosinófilos ≥150 células/µL, FeNO ≥25 ppb y espirometría con patrón obstructivo. Resultados: Se incluyeron 6 pacientes mujeres con diagnóstico de Asma grave. Valores iniciales de eosinófilos de 180 ­ 630 cél/µL, IgE 176 ­ 2500 Ui/ml, FENO 23 -39, ACT a los 2, 4 y 6 meses de uso, mínima de 9 y final máxima de 25. Mejoría considerable en la prueba ACT desde los primeros dos meses de uso, dismi- nucion de esteroide inhalado y 0 a 2 exacerbaciones en 6 meses. Conclusiones: Existen múltiples estudios, no se cuenta con reportes estadísticamente significativos para demostrar superioridad con el uso de algún biológico en específico, aunado a las diferentes limitantes económicas que existen en el país. Es necesario identificar poblaciones objetivo con los fenotipos que responderán a una terapia específica y dirigir el tratamiento. En México hay pocos centros hospitalarios con estas terapias, es necesario continuar con la evaluación constante y aporte de información para poder encontrar el tratamiento idóneo para la población mexicana.

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.

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.

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.

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.

Relation of serum IL-32 levels and gene polymorphism rs45499297 with obesity in Mexican patients: a laboratory and in silico analysis.

Introduction: Background: many genes have been involved in the development of obesity. Interleukin 32 (IL-32) is a proinflammatory cytokine; rs45499297 is a T/C promoter, single-nucleotide polymorphism of the IL32 gene. Objectives: this study aimed to evaluate the rs45499297 polymorphism and its association with obesity. Another objective of this study was to carry out an in silico analysis. Methods: this study was cross-sectional, and included 333 subjects classified by body mass index and fat percentage. The plasma glucose and lipid profile were measured. We measured serum IL-32 protein by ELISA and the rs45499297 polymorphism by PCR-RFLP. We used several databases to build the IL32 gene network and infer transcription factors that bind to this polymorphic site. Results: subjects underweight and with low fat percentages had lower levels of IL-32. CT genotype and allele C were less frequent in the overweight/obesity group than in the normal-weight group. Interestingly, this result remained only in the male gender. We found that the transcription factors Hepatocyte Nuclear Factor and Specificity Protein 1 bind to this polymorphic site. In addition, we infer that IL32 is involved in metabolic pathways related to viral infections. Conclusion: the TC genotype is associated with overweight/obesity. The decrease in levels of IL-32 observed in underweight and low fat percentage groups could be due to an impaired inflammatory profile. The in silico analysis showed that several transcriptional factors bind at this polymorphic site, and that the enrichment of the metabolic pathways is diverse.

Introducción: Introducción: la interleucina 32 es una citocina proinflamatoria. El rs45499297 es un polimorfismo de nucleótido simple del gen de IL32, situado en la región promotora y caracterizado por un cambio de T/C. Objetivo: evaluar el polimorfismo rs45499297 y su asociación con la obesidad, y realizar un análisis in silico. Métodos: el estudio fue transversal e incluyó 333 sujetos clasificados por índice de masa corporal y porcentaje de grasa. Se midieron la glucosa y el perfil lipídico, así como los niveles séricos de IL-32 mediante ELISA y el genotipo del polimorfismo rs45499297 mediante PCR-RFLP. Para el análisis in silico se utilizaron varias bases de datos para hacer la red de genes de IL32 e inferir factores de transcripción unidos al sitio polimórfico. Resultados: los sujetos con bajo peso y bajo porcentaje de grasa tienen niveles más bajos de IL-32. El genotipo TC y el alelo C se encontraron con menos frecuencia en los sujetos con sobrepeso/obesidad que en los normopeso, resultado que permaneció solo en el género masculino. Se encontró que el factor nuclear de los hepatocitos y la proteína de especificidad 1 se unen a este sitio polimórfico. Se infiere que IL32 está involucrado en vías metabólicas relacionadas con las infecciones virales. Conclusión: el genotipo TC está asociado al sobrepeso/la obesidad. La disminución de los niveles de IL-32 observada en los sujetos con bajo peso y bajo porcentaje de grasa podría ser por un perfil inflamatorio alterado. El análisis in silico mostró que varios factores de transcripción se unen al sitio polimórfico y que el enriquecimiento de las vías metabólicas es diverso.

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.

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

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.

[Serum cytokines in ANCA-associated vasculitis: Correlation with disease-related clinical and laboratory findings]. / Citocinas séricas en la vasculitis asociada a ANCA: correlación con los hallazgos clínicos y de laboratorio relacionados con la enfermedad.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic, autoimmune disease. Cytokine dysregulation during active disease and clinical remission, reflects significant immunological activity in various disease stages, and might be responsible for the potential relapse of ANCA-vasculitis. OBJECTIVES: This study aimed to screen serological profiles in active granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and to determine their associations with clinical characteristics. MATERIALS AND METHODS: Serum IL-10, IL-12, IL-17, IL-21, IL-23, B cell activating factor (BAFF) concentrations were determined by Quantikine HS ELISA in 71 patients, 47 with GPA and 24 with MPA, and compared with 16 healthy controls. Subsequently, the correlations between serum IL-10, IL-12, IL-17, IL-21, IL-23, BAFF levels, and both laboratory and clinical abnormalities were investigated. RESULTS: BAFF levels were significantly higher in GPA than MPA, and healthy controls. IL-10 and BAFF levels were elevated in GPA patients with pulmonary involvement. Higher BAFF levels might reflect severe GPA. IL-10 and IL-12 levels were higher in MPA than GPA. In MPA, IL-10 levels were highest in patients with short disease duration, and young individuals. IL-12 correlated positively with BVAS and was elevated in patients with cardiovascular involvement and nasal S. aureus carriers. CONCLUSIONS: In MPA, IL-12 correlates positively with disease activity, and is significantly increased in patients with cardiovascular involvement and nasal S. aureus carriers. Increased IL-10 is observed in young MPA patients and in those with short MPA duration. Elevated BAFF and IL-10 levels are associated with pulmonary involvement in GPA. High BAFF levels might reflect severe GPA.

Effect of exposure to low doses of ozone on interleukin 17A expression during progressive neurodegeneration in the rat hippocampus.

INTRODUCTION: Chronic exposure to low doses of ozone causes oxidative stress and loss of regulation of the inflammatory response, leading to progressive neurodegeneration. OBJECTIVE: We studied the effect of chronic exposure to low doses of ozone on IL-17A concentration and expression in neurons, microglia, astrocytes, and T cells in the rat hippocampus. METHODS: We used 72 Wistar rats, divided into 6 groups (n=12): a control group (no ozone exposure) and 5 groups exposed to ozone (0.25ppm, 4h daily) for 7, 15, 30, 60, and 90 days. We processed 6 rats from each group to quantify IL-17A by ELISA; the remaining 6 were processed for immunohistochemistry (against IL-17A and GFAP, Iba1, NeuN, and CD3). RESULTS: The ELISA study data showed a significant increase in IL-17A concentrations in the 7-, 15-, 30-, and 60-day exposure groups, with regard to the control group (P<.05). Furthermore, they indicate that hippocampal neurons were the cells showing greatest immunoreactivity against IL-17A between 60 and 90 days of exposure to ozone; we also observed an increase in activated astrocytes in the 30- and 60-day exposure groups. CONCLUSION: Exposure to ozone in rats induces an increase in IL-17A expression, mainly in hippocampal neurons, accompanied by hippocampal astrocyte activation during chronic neurodegeneration, similar to that observed in Alzheimer disease in humans.