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

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

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

Effect of coinfection with influenza virus and bacteria on host damage.

BACKGROUND: Influenza virus infection is often complicated by a bacterial infection, with this coinfection causing severe pneumonia. If not timely treated, the disease can cause death. OBJECTIVE: To demonstrate, in animal models, that coinfection with influenza virus and bacteria that affect the respiratory tract causes multisystemic damage. METHOD: Six groups of mice were formed: a control group, one infected with the influenza virus, two infected with bacteria: Haemophilus influenzae and Streptococcus pneumoniae, respectively; and two co-infected with influenza virus and Haemophilus influenzae or Streptococcus pneumoniae, respectively. RESULTS: Of the six groups of mice, only the group co-infected with influenza virus and Streptococcus pneumoniae showed damage to thoracic and abdominal organs. A decrease in serum cytokine levels was found in all study groups, which was more pronounced in the co-infected mice. CONCLUSIONS: The groups of mice infected with Streptococcus pneumoniae or influenza virus alone showed no damage, which indicates that coexistence of these infections caused the damage in the group of co-infected mice.

ANTECEDENTES: La infección por el virus de la influenza con frecuencia se complica con una infección bacteriana, coinfección que provoca cuadros graves de neumonía, la cual puede ocasionar la muerte si no es tratada en forma oportuna. OBJETIVO: Demostrar en modelos animales que la coinfección por el virus de la influenza y bacterias que afectan el tracto respiratorio ocasiona daño multisistémico. MÉTODO: Se formaron seis grupos de ratones: un grupo control, uno infectado de virus de la influenza, dos infectados de bacterias: Haemophilus influenzae y Streptococcus pneumoniae, respectivamente; y dos coinfectados de virus de la influenza y Haemophilus influenzae y Streptococcus pneumoniae, respectivamente. RESULTADOS: De los seis grupos de ratones, solo en el grupo coinfectado de virus de la influenza y Streptococcus pneumoniae se observó daño en órganos torácicos y abdominales. En todos los grupos se encontró disminución de los niveles séricos de las citocinas, mayor en los ratones coinfectados. CONCLUSIONES: Los grupos de ratones infectados solo de Streptococcus pneumoniae o el virus de la influenza no presentaron daños, lo cual indica que la coexistencia de estas infecciones fue la que ocasionó el daño en el grupo de ratones coinfectados.

[Actualidades en la inmunopatología de la esclerosis múltiple].

Multiple sclerosis is a demyelinating inflammatory disease that affects the central nervous system. Its etiology is the result of a complex interaction between genetic and environmental factors that trigger a deregulated immune response, with the resulting inflammation and neuronal/axonal degeneration. Neuroinflammation is triggered when peripheral leukocytes migrate to the central nervous system and release cytokines such as interleukins 1 and 6 (IL-1 and 6) and tumor necrosis factor (TNF), which act on dwelling cells. The innate immune system plays an important role in the onset and progression of the disease by identifying molecular patterns associated with pathogens and damage, which modulate effector and regulatory functions of the cells where they are expressed, in order to direct the specific immune response. Th17 cells favor the disruption of the blood-brain barrier, which enables the migration of leukocytes to the central nervous system and the triggering of the inflammatory cascade; the Th1 profile (IL-1, IL-6) collaborates to perpetuate it. B-cell function is to produce antibodies and cytokines (IL-6, IL-12 and TFN). Knowledge on multiple sclerosis pathophysiology will enable the development of new therapeutic options that impact on natural history of the disease and its prognosis.

La esclerosis múltiple es una enfermedad inflamatoria desmielinizante que afecta el sistema nervioso central. Su etiología es el resultado de una compleja interacción entre factores genéticos y ambientales que desencadenan una respuesta inmune desregulada, con la consiguiente inflamación y degeneración neuronal/axonal. La neuroinflamación se desencadena cuando los leucocitos periféricos migran al sistema nervioso central y liberan citocinas como interleucinas 1 y 6 (IL-1, IL-6) y factor de necrosis tumoral (TNF), que actúan sobre células residentes del mismo. El sistema inmune innato desempeña un papel importante en el inicio y progresión de la enfermedad, mediante la identificación de patrones moleculares asociados con patógenos y daño, que modulan las funciones efectoras y reguladoras de las células donde se expresan, para dirigir la respuesta inmune específica. Las células Th17 favorecen la disrupción de la barrera hematoencefálica, que permite la migración de leucocitos al sistema nervioso central y desencadena la cascada de la inflamación; el perfil Th1 (IL-1, IL-6) colabora para perpetuarla. La función de las células B es la producción de anticuerpos y citocinas (IL-6, IL-12 y TFN). Conocer la fisiopatología de la esclerosis múltiple permitirá desarrollar nuevas opciones terapéuticas que impacten en la historia natural de la enfermedad y su pronóstico.

Proinflammatory and anti-inflammatory cytokine profile in pediatric patients with irritable bowel syndrome.

BACKGROUND AND OBJECTIVES: There is evidence that patients with irritable bowel syndrome (IBS) have a low degree of inflammation in the intestinal mucosa. The aim of the study was to evaluate the profile of pro- and anti-inflammatory cytokines in plasma in Mexican pediatric patients with IBS. PATIENTS AND METHODS: Fifteen patients with IBS according to Rome III criteria for childhood and 15 healthy children, matched by age and sex, were included in the study. Plasma levels of tumoral necrosis factor alpha (TNF-α), interleukins 10 and 12 (IL-10, IL-12) and transforming growth factor beta (TGF-ß) were quantified and compared between groups. RESULTS: Plasma levels of IL-10 were lower in patients with IBS (86.07+21.3 pg/mL vs. 118.71+58.62 pg/mL: P=.045) and IL-12 levels were higher in patients with IBS compared to the control group of healthy children (1,204.2±585.9 pg/mL vs. 655.04±557.80 pg/mL; P=.011). The IL-10/IL-12 index was lower in patients with IBS (0.097±0.07 vs. 0.295±0.336; P=.025). Plasma concentration of TGF-ß was higher in patients with IBS (545.67±337.69 pg/mL vs. 208.48±142.21 pg/mL; P=.001). There was no difference in plasma levels of TNF-α between groups. CONCLUSIONS: This study suggests that children with IBS have a state of altered immune regulation. This is consistent with the theory of low-grade inflammatory state in these patients. Further studies are needed to elucidate the role played by these cytokines, specifically TGF-ß in the pathogenesis of IBS.

Cardioprotective effect of chelidonic acid against doxorubicin-induced cardiac toxicity in rats.

INTRODUCTION AND OBJECTIVES: The current study evaluates the effect of chelidonic acid on doxorubicin-induced cardiac toxicity. Chelidonic acid (CA) is a natural pyran-skeleton heterocyclic compound found in rhizomes of the perennial plant, celandine (Chelidonium majus). METHODS: Wistar rats were given an intraperitoneal injection of doxorubicin (1.25 mg/kg, cumulative dose of 20 mg/kg) four times per week for a duration of four weeks to induce cardiotoxicity. CA treatment (10, 20, and 40 mg/kg orally for four weeks) was started together with doxorubicin. RESULTS: CA treatment reduced myocardial damage and improved cardiac dysfunction in doxorubicin-treated rats. It improved blood pressure, restored ST wave height and normalized the QTc interval compared to the rats treated only with doxorubicin. Administration of CA for four weeks reduced left ventricular end-diastolic pressure. Moreover, CA treatment decreased the level of cardiac markers such as creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and cardiac troponin-T. Masson's trichrome, hematoxylin, and eosin staining of heart tissue revealed that CA attenuated the deleterious effects of doxorubicin and prevented further damage and fibrosis in rats. CONCLUSION: The study findings confirm that CA treatment can protect the myocardium against doxorubicin-induced cardiotoxicity.

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

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

Catastrophic antiphospholipid syndrome: Lessons from the "CAPS Registry".

The catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening clinical condition that represents the most severe clinical presentation of the antiphospholipid syndrome (APS). It was first described in 1992 in a group of patients that presented with multiorgan involvement and microangiopathic features of APS. Most of the current knowledge of CAPS comes from the analysis of all cases collected at the "CAPS Registry" that was created in 2000 to perform studies on this condition. Most cases are triggered by a prothrombotic situation that leads to a multiorgan thrombosis and a cytokine storm. The analysis of cases included in the "CAPS Registry" has shown that the triple therapy with anticoagulation, glucocorticoids, and plasma exchange and/or intravenous immunoglobulins is associated to a better prognosis of CAPS. The improvement of the knowledge allowed a decrease from the 50% mortality rate reported in the first series to 25-30% in the most recent publications.

Increased circulating interleukin-23 level in patients with sarcoidosis.

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

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

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

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

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.

Association of Fusobacterium nucleatum infection and colorectal cancer: A Mexican study.

INTRODUCTION AND AIMS: Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Many risk factors are involved, and current evidence links the gut microbiota and colorectal carcinogenesis. Fusobacterium nucleatum (F. nucleatum) is proposed as one of the risk factors at the onset and during the progression of CRC, due to immune system and inflammatory modulation. MATERIALS AND METHODS: Ninety samples from three different regions of the colon were collected through colonoscopy in patients with CRC, and qPCR TagMan® was conducted to detect F. nucleatum and cytokines (IL-17, IL-23, and IL-10) in tumor, peritumor, and normal samples. The differences between them were analyzed and correlated. RESULTS: The abundance of F. nucleatum determined through the 2-ΔΔCt method in CRC (7.750 [5.790-10.469]) was significantly higher than in the normal control (0.409 [0.251-0.817]) (p < 0.05). There was no significant association between F. nucleatum and the cytokines (p > 0.05). CONCLUSIONS: CRC is a heterogeneous disease that presents and progresses in a complex microenvironment, partially due to gut microbiome imbalance. F. nucleatum was enriched in CRC tissue, but whether that is a cause of the pathology or a consequence, has not yet been clearly defined.

Inflammation and atherogenic markers in patients with type 2 diabetes mellitus. / Marcadores aterogénicos y de inflamación en pacientes con diabetes mellitus tipo 2.

Type two diabetes mellitus (T2DM) is characterized by a chronic inflammation status. Altered markers such as lipid concentrations are usually found in this disease. Elevated inflammation markers have been described such as cytokines (interleukin 6, tumour necrosis factor-alpha, and IL-8). However, there is a lack of information about the behaviour of the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), lipid coefficients, and atherogenic index in T2DM. OBJECTIVE: To describe the atherogenic and inflammation parameters in a group of patients with T2DM. MATERIALS AND METHODS: 42 patients with T2DM were included, all patients were surveyed on clinic history (disease history, comorbidity, smoking, and other relevant variables), measurements of haematological, biochemical, and anthropometric parameters were taken and atherogenic coefficients and inflammation ratios were calculated. RESULTS: Inflammation markers such as interleukin 6 and 8, necrosis tumour factor, and NLR were elevated. Of the patients, 88% were classified as high risk according to the atherogenic index. Former smokers had lower levels of IL-8 and higher NLR than non-smokers. CONCLUSION: The atherogenic and inflammation markers such as atherogenic index, IL-8, and NLR make it possible to identify a subgroup of patients that are at risk of severe complications and mortality.

Association of Fusobacterium nucleatum infection and colorectal cancer: A Mexican study. / Asociación entre infección por Fusobacterium nucleatum y cáncer colorrectal: un estudio mexicano.

INTRODUCTION AND AIMS: Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Many risk factors are involved, and current evidence links the gut microbiota and colorectal carcinogenesis. Fusobacterium nucleatum is proposed as one of the risk factors at the onset and during the progression of CRC, due to immune system and inflammatory modulation. MATERIALS AND METHODS: Ninety samples from three different regions of the colon were collected through colonoscopy in patients with CRC, and qPCR TagMan® was conducted to detect F. nucleatum and cytokines (IL-17, IL-23, and IL-10) in tumor, peritumor, and normal samples. The differences between them were analyzed and correlated. RESULTS: The abundance of F. nucleatum determined through the 2-ΔΔCt method in CRC (7.750 [5.790-10.469]) was significantly higher than in the normal control (0.409 [0.251-0.817]) (p<0.05). There was no significant association between F. nucleatum and the cytokines (p>0.05). CONCLUSIONS: CRC is a heterogeneous disease that presents and progresses in a complex microenvironment, partially due to gut microbiome imbalance. F. nucleatum was enriched in CRC tissue, but whether that is a cause of the pathology or a consequence, has not yet been clearly defined.

Therapeutic options for the management of severe COVID-19: A rheumatology perspective.

The novel SARS-CoV-2 human coronavirus in Wuhan, China, has triggered a worldwide respiratory disease outbreak (COVID-19). Acute respiratory distress syndrome (ARDS), multiorgan dysfunction and thrombotic events are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a "cytokine storm", also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. In addition to anti-viral therapy and supportive treatment in critically ill patients, unique medications for this condition are also under investigation. Here we reviewed therapeutic options, including the antibody therapy that might be an immediate strategy for SARS-CoV-2 therapy.

Oral administration of n-3 fatty acids positively affect the mucosal lesions after experimental ischemic enteritis in the rat.

AIM: The purpose of the study was to evaluate the effect of oral administration of n-3 polyunsaturated fatty acids in experimental ischemic enteritis in rats. METHODS: Forty Wistar rats were submitted to control narrowing of the superior mesenteric artery and were divided in two groups: N3 polyunsaturated fatty acids, which received a high-molecular polymer solution of artificial total enteral nutrition enriched with n-3 fatty acids and CONTROL which received a high-molecular polymer solution of artificial total enteral nutrition. RESULTS: Reduction of the animals' body weight was observed in both groups, but there was no difference between the two groups. Regarding the level of cytokines interleukin (IL)-1b, IL-6, and tumor necrosis factor a (TNF-a) there was no statistically significant difference between the two groups. Ischemic lesions to the small bowel mucosa were observed in both groups. A statistically significant difference in the extent of intestinal lesions was observed between the two groups with the animals that received enteral nutrition enriched with n-3 fatty acid developing fewer lesions. CONCLUSION: Enteral nutrition enriched with n-3 polyunsaturated fatty acids reduces the mucosal lesions caused by mesenteric ischemia compared to standard enteral nutrition, by modifying the local, but not the systemic, immune, and inflammatory response.

OBJETIVO: El propósito del estudio fue evaluar el efecto de la administración oral de ácidos grasos poliinsaturados n-3 en enteritis isquémica experimental en ratas. MÉTODOS: 40 ratas Wistar fueron sometidas a un estrechamiento controlado de la arteria mesentérica superior y se dividieron en dos grupos: N3PUFA, que recibieron una solución de polímero de alto peso molecular de nutrición enteral total artificial enriquecida con ácidos grasos n-3 y CONTROL que recibió un alto -Solución de polímero molecular de nutrición enteral total artificial. RESULTADOS: Se observó una reducción del peso corporal de los animales en ambos grupos, pero no hubo diferencias entre los dos grupos. Con respecto al nivel de citocinas IL-1b, IL-6 y TNF-a, no hubo diferencia estadísticamente significativa entre los dos grupos. Se observaron lesiones isquémicas de la mucosa del intestino delgado en ambos grupos. Se observó una diferencia estadísticamente significativa en la extensión de las lesiones intestinales entre los dos grupos y los animales que recibieron nutrición enteral enriquecida con ácido graso n-3 desarrollaron menos lesiones. CONCLUSIÓN: La nutrición enteral enriquecida con ácidos grasos poliinsaturados n-3 reduce las lesiones mucosas causadas por isquemia mesentérica en comparación con la nutrición enteral estándar, al modificar la respuesta local, pero no sistémica, inmunitaria e inflamatoria.

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

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).

[Effectiveness of corticoid pulses in patients with cytokine storm syndrome induced by SARS-CoV-2 infection]. / Eficacia de los pulsos de corticoides en pacientes con síndrome de liberación de citocinas inducido por infección por SARS-CoV-2.

INTRODUCTION: Cytokine storm syndrome (CSS) is a serious complication of COVID-19 patients. Treatment is tocilizumab. The use of glucocorticoids (GC) is controversial. In other very similar CSS, such as macrophage activation syndrome (MAS) and hemophagocytic syndrome (HFS), the main treatment are corticosteroids. Our objective is to evaluate the efficacy of GC in the CSS by COVID-19. PATIENTS: We included 92 patients with CSS associated to COVID-19 who received GC, GC, and tocilizumab and only tocilizumab. We determine CSS markers. We evaluated mortality, intubation, and a combined variable. RESULTS: In all cases the percentages of events were lower in the group of patients with GC was administered. The hazard ratio of the final variables with GC versus the group in which only tocilizumab was administered was lower as CGs were considered, with statistical significance for survival. DISCUSSION: The early use of GC pulses could control SLC, with a lower requirement to use tocilizumab and a decrease in events such as intubation and death.

The role of astrocytes in multiple sclerosis pathogenesis. / Participación de los astrocitos en la patogénesis de la esclerosis múltiple.

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS), in which astrocytes play an important role as CNS immune cells. However, the activity of astrocytes as antigen-presenting cells (APC) continues to be subject to debate. DEVELOPMENT: This review analyses the existing evidence on the participation of astrocytes in CNS inflammation in MS and on several mechanisms that modify astrocyte activity in the disease. CONCLUSIONS: Astrocytes play a crucial role in the pathogenesis of MS because they express toll-like receptors (TLR) and major histocompatibility complex (MHC) classI andII. In addition, astrocytes participate in regulating the blood-brain barrier (BBB) and in modulating T cell activity through the production of cytokines. Future studies should focus on the role of astrocytes in order to find new therapeutic targets for the treatment of MS.

Changes in metabolic and inflammatory parameters in a type 1 diabetic patient performing extreme activities.

INTRODUCTION: Background: physical activity in type 1 diabetic patients allows a better control of glycaemia and glycosylated hemoglobin, helps to maintain a residual endocrine pancreatic mass and optimizes subsequent insulin requirements. These improvements might be due in part to increases in anti-inflammatory cytokines that could help to minimize ß-cell destruction. However, type, intensity and frequency of exercise for type 1 diabetic patients remain to be established. Case report: we present the case of a 48-year-old man diagnosed with type 1 diabetes at the age of 23. He is a professional alpinist and recently was recruited in a program of the Yuri Gagarin Cosmonaut Training Center (Russia) to be the first diabetic astronaut. Metabolic and inflammatory responses were assessed after performing two extreme activities. Discussion: well programmed extreme activities accompanied by a correct dietetic intervention can reduce the adverse metabolic and inflammatory processes that appear due to exercise and diabetes.

INTRODUCCIÓN: Introducción: la actividad física en pacientes diabéticos tipo 1 permite un mejor control de la glucemia y hemoglobina glucosilada, ayuda a mantener una masa residual de páncreas endocrino y optimiza las necesidades de insulina. Estas mejoras podrían ser debidas en parte al incremento en citocinas antiinflamatorias que ayudarían a minimizar la destrucción de células ß. Sin embargo, el tipo, la intensidad y la frecuencia de ejercicio para pacientes diabéticos tipo 1 no han sido establecidos. Caso clínico: presentamos el caso de un varón de 48 años de edad diagnosticado de diabetes tipo 1 a los 23. Es alpinista profesional y recientemente ha sido reclutado por el Centro de Entrenamiento para Cosmonautas Yuri Gagarin (Rusia) para ser el primer astronauta diabético. Hemos comparado respuestas metabólicas e inflamatorias tras realizar dos actividades extremas. Discusión: actividades extremas bien programadas y con una correcta intervención dietética pueden reducir la descompensación metabólica e inflamatoria causada por la combinación actividad-enfermedad.

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

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