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The IGRA (Interferon Gamma Release Assays) test is currently the standard specific test for Mycobacterium tuberculosis infection status. However, a positive test cannot distinguish between active tuberculosis disease (ATBD) and latent tuberculosis infection (LTBI). Developing a test with this characteristic is needed. We conducted longitudinal studies to identify a combination of antigen peptides and cytokines to discriminate between ATBD and LTBI. We studied 54 patients with ATBD disease and 51 with LTBI infection. Cell culture supernatant from cells stimulated with overlapping Mycobacterium tuberculosis novel peptides and 40 cytokines/chemokines were analyzed using the Luminex technology. To summarize longitudinal measurements of analyte levels, we calculated the area under the curve (AUC). Our results indicate that in vitro cell stimulation with a novel combination of peptides (Rv0849-12, Rv2031c-14, Rv2031c-5, and Rv2693-06) and IL-1RA detection in culture supernatants can discriminate between LTBI and ATBD.
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Introducción: El desacondicionamiento físico se asocia con disminución en la capacidad cardiorrespiratoria, aumento en el contenido de grasa corporal, e imbalances en respuesta inflamatoria, todos ellos factor de riesgo frente a la agresión de una intervención quirúrgica mayor. El valor de consumo de oxígeno (VO2max), el índice de masa corporal (IMC) y los valores plasmáticos de citoquinas de pacientes programados para una intervención quirúrgica mayor abdominal a menudo no se tienen en cuenta en la valoración prequirúrgica. Objetivo: Determinar la condición física e inflamatoria de pacientes que se trataron con una intervención quirúrgica mayor abdominal. Métodos: Investigación cuantitativa, descriptiva. Muestra por conveniencia de pacientes que se trataron con una intervención quirúrgica mayor abdominal en dos hospitales de Manizales (Colombia). Previo a la intervención, se midió VO2max, el IMC y valores de citoquinas. Resultados: Participaron en el estudio 6 hombres y 48 mujeres. Los valores promedio del VO2max se categorizaron como bajos. Se encontraron valores altos de IMC, del receptor antagonista de IL-1 (IL-1 Ra) y del factor neutrotrófico derivado del cerebro (BDNF). No se hallaron diferencias significativas en los valores promedio de VO2max, de IL-1Ra y de BDNF entre los grupos. Los pacientes programados para intervención quirúrgica ginecológica y gastrointestinal tuvieron sobrepeso y los programados para intervención quirúrgica bariátrica fueron obesos mórbidos. Conclusión: Pacientes programados para una intervención quirúrgica mayor abdominal presentan valores bajos de VO2max para la edad y altos de IMC. Se hallaron valores altos de IL-1Ra y de BDNF asociadas a obesidad y a posible antiinflamación(AU)
Introduction: Physical deconditioning is associated with, a decrease in cardiorespiratory capacity, an increase in body fat content and imbalances in the inflammatory response, all of which are risk factors for the aggression of a major surgical intervention. The oxygen consumption value (VO2max), body mass index (BMI), and plasma cytokine values of patients scheduled for major abdominal surgery are often not taken into account in the presurgical evaluation. Objective: To determine the physical and inflammatory condition of patients who were treated with a major abdominal surgery. Methods: Quantitative, descriptive research. Convenience sample of patients who underwent major abdominal surgery in two hospitals in Manizales (Colombia). Prior to the intervention, VO2max, BMI and cytokine values were measured. Results: 6 men and 48 women participated in the study. Average VO2max values were categorized as low. High values of BMI, IL-1 receptor antagonist (IL-1 Ra) and brain derived neutrotrophic factor (BDNF) were found. No significant differences were found in the mean VO2max, IL-1Ra and BDNF values between the groups. Patients scheduled for gynecological and gastrointestinal surgery were overweight and those scheduled for bariatric surgery were morbidly obese. Conclusion: Patients scheduled for major abdominal surgery have low VO2max values for age and high BMI. High IL-1Ra and BDNF values were found associated with obesity and possible anti-inflammation(AU)
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Abdome/cirurgia , Anestesia/efeitos adversosRESUMO
Since distinguishing pulmonary (PTB) from latent tuberculosis (LTBI) in pediatric patients remains a challenge, we aimed to investigate the efficacy of immune mediators in diagnosing PTB and LTBI in this population. In this cross-sectional study performed with children and adolescents, serum levels of 20 biomarkers were assessed and data were analyzed according to age groups. We included 65 participants (PTB, n = 28 and LTBI, n = 37). Overall, levels of TNF-α, IL-1Ra, IL-6, IL-17A, VEGF, MMP-1, and procalcitonin were significantly higher (P < 0.05) in adolescents and children <10 years-old with PTB. Also, principal component analysis (PCA) showed that immune mediators were able to distinguish PTB from LTBI. VEGF and IL-1Ra presented the highest area under the curve (AUC) values, both separately (AUC 0.890 and 0.785) and combined (AUC 0.99). Taken together, we showed that VEGF and IL-1Ra are promising biomarkers to distinguish PTB from LTBI in pediatric patients, especially in children <5 years-old.
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Tuberculose Latente , Mycobacterium tuberculosis , Adolescente , Biomarcadores , Criança , Pré-Escolar , Estudos Transversais , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Receptores de Interleucina-1 , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Many alternative treatments aimed at modulating osteoarthritis (OA) progression have been developed in the past decades, including the use of cytokine inhibitors. IL-1ß is considered one of the most impactful cytokines in OA disease and therefore, its blockage offers a promising approach for the modulation of OA. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory protein belonging to the IL-1 family that competes with IL-1ß for occupancy of its receptors, without triggering the same downstream inflammatory response. Because of its natural anti-inflammatory properties, different methods have been proposed to use IL-1Ra therapeutically in OA. Autologous conditioned serum (ACS) and autologous protein solution (APS) are blood-derived products produced with the use of specialized commercial kits. These processes result in hemoderivatives with high concentrations of IL-1Ra and other cytokines and growth factors with potential modulatory effects on OA progression. Several studies have demonstrated potential anti-inflammatory effect of these therapies with promising clinical results. However, as with any hemoderivatives, clinical outcomes may vary. For optimal therapeutic use, further research is warranted for a more comprehensive understanding of the product's composition and interaction of its components in joint inflammation. Additionally, differences between ACS and APS treatments may not be clear for many clients and clinicians. Thus, the objective of this narrative review is to guide the reader in important aspects of ACS and APS therapies, in vitro and in vivo applications and to compare the use of both treatments in OA.
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PURPOSE: The present study measured 41 soluble mediators in the tear of 19 patients with age-related cataract and 32 healthy adults as controls. MATERIALS AND METHODS: This was a prospective, case-control study in which, using multiple immunoassays, we measured in tear samples the following molecules: EGF, FGF-2, Eotaxin, TGF-α, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFN-α2, IFN-γ, GRO, IL-10, MCP-3, IL-12p40, MDC, IL-12p70, PDGF-AA, IL-13, PDGF-AB/BB, IL-15, sCD40L, IL-17a, IL-1ra, IL-1α, IL-9, IL-1ß, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MIP-1α, MIP-1ß, RANTES, TNFα, TNFß, VEGF. Statistical analyses were done by multiple adjusted models and p values were corrected by the Benjamini and Hochberg method. RESULTS: We did not find significant differences in the amount of the tested molecules in the tear fluid between cataract patients and controls. Correlation analyses relative to age were carried out for both groups. Analysis of MCP-1 tear levels revealed a direct correlation with age for normal healthy controls as well as for cataract patients. But IL-6 tear levels correlated with age only in the group of cataract patients. In addition, IL1-ra tear levels correlated with cataract nuclear grade; higher grades were associated with higher IL-1ra concentrations. CONCLUSIONS: Our results suggest that ocular aging is accompanied by increased production of IL-6 and MCP-1, which can be measured in tear fluid. ABBREVIATIONS: AMD: Age-Related Macular Degeneration; EGF: Epidermal growth factor; Eotaxin: Eosinophil chemotactic proteins; FasL: Fas ligand; FGF-2: Basic fibroblast growth factor 2; Flt-3L: Fms related tyrosine kinase 3 ligand; G-CSF: Granulocyte colony stimulating factor; GM-CSF: Granulocyte macrophage colony stimulating factor; GRO: Growth regulated protein; HGF: Human growth factor; ICAM-1: Intercellular adhesion molecule-1; IFNα2: Interferon alpha 2; IFNγ: Interferon gamma; IL: Interleukin; IL-1ra: Interleukin-1 receptor antagonist; IL-12p40: Interleukin-12 subunit p40; IL-12p70: Interleukin-12 subunit p70; IP-10: Interferon gamma-induced protein 10; MCP-1: Monocyte chemotactic protein 1; MCP-3: Monocyte chemotactic protein 3; MDC: Macrophage derived chemokine; MIG: Monokine induced by gamma interferon; MIP-1α: Macrophage inflammatory proteins 1 alpha; MIP-1ß: Macrophage inflammatory proteins 1 beta; MMPs: Matrix metalloproteinases; MMP-9: Matrix metalloproteinase 9; PAI1: Plasminogen activator inhibitor 1; PDGF-AA: Platelet-derived growth factor subunit AA; PDGF-AB/BB: Platelet-derived growth factor subunit AB and BB; PIGF: Placenta growth factor; RANTES: Regulated on activation, normal T cell expressed and secreted; SAA: Serum amyloid A; sCD40L: Soluble CD40 ligand; sTNF-RII: Soluble tumor necrosis factor receptor; TBUT Tear breakup time; TGF-α: Transforming growth factor alpha; TGF-ß: Transforming growth factor beta; TNFα: Tumor necrosis factor alpha; TNFß: Tumor necrosis factor beta; VCAM: Vascular cell adhesion molecule; VEGF: Vascular endothelium growth factor.
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Catarata/metabolismo , Citocinas/metabolismo , Proteínas do Olho/metabolismo , Lágrimas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Quimiocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: This study compared the effects of 12â¯weeks of high-intensity interval body weight training (HIBWT) with combined training (COMT; aerobic and resistance exercises on body composition, a 6-minute walk test (6MWT; physical performance), insulin resistance (IR) and inflammatory markers in postmenopausal women (PW) at high risk of type 2 diabetes mellitus (TDM2). METHODS: In this randomized controlled clinical study, 16 PW at high risk of TDM2 were randomly allocated into two groups: HIBWT (nâ¯=â¯8) and COMT (nâ¯=â¯8). The HIBWT group performed a training protocol (length time ~28â¯min) consisting of ten sets of 60â¯s of high intensity exercise interspersed by a recovery period of 60â¯s of low intensity exercise. The COMT group performed a training protocol (length time ~60â¯min) consisting of a 30â¯min walk of moderate intensity following by five resistance exercises. All training sessions were performed in the university gym facility three days a week (no consecutive days) for 12â¯weeks. All outcomes (body composition, muscle function, and IR and inflammatory markers) were assessed at the baseline and at the end of the study. RESULTS: Both groups increased (Pâ¯<â¯0.05) muscle mass index (MMI), 6MWT, and interleukin 1 receptor antagonist and decreased fasting glucose, glycated hemoglobin, Insulin, HOMA-IR, and monocyte chemoattractant protein-1 (trend, Pâ¯=â¯0.056). HIBWT effects were indistinguishable (Pâ¯>â¯0.05) from the effects of COMT. There was a significant (Pâ¯<â¯0.05) interaction of time by the group in muscle strength, indicating that only the COMT increased the muscle strength. CONCLUSIONS: This study suggests that changes in HOMA, IL-1ra, 6MWT, and MMI with HITBW are similar when compared to COMT in PW at high risk of TDM2. TRIAL REGISTRATION: The patients were part of a 12-week training study (ClinicalTrials.gov Identifier: NCT03200639).
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Composição Corporal , Diabetes Mellitus Tipo 2/prevenção & controle , Treinamento Intervalado de Alta Intensidade , Músculo Esquelético/fisiologia , Treinamento Resistido/métodos , Idoso , Biomarcadores/metabolismo , Glicemia/análise , Índice de Massa Corporal , Feminino , Hemoglobinas Glicadas/análise , Humanos , Insulina/metabolismo , Pessoa de Meia-Idade , Desempenho Físico Funcional , Pós-MenopausaRESUMO
It has been reported that an increased function of the P2X7 purinergic receptor is associated with an increase in both insulin sensitivity and secretion. Accordingly, we explored the possible effect of the 1068 G>A polymorphism of the gene P2RX7 on glucose homeostasis and the levels of the anti-inflammatory cytokine IL-1Ra in T2D patients. The presence of the 1068 G>A polymorphism in T2D patients (nâ¯=â¯100) and healthy subjects (nâ¯=â¯100) was determined by DNA sequencing, and serum levels of IL-1Ra were measured by ELISA. Pancreatic ß-cell function, insulin resistance, blood glucose levels and glycated hemoglobin (HbA1c) were also analyzed. We detected a significant negative association between T2D and the 1068 G>A SNP (Odds ratio 0.3916, pâ¯=â¯0.0045). In addition, we observed that T2D patients bearing the 1068 G>A variant showed higher serum levels of IL-1Ra compared to both, patients with the GG genotype or healthy individuals (GG or G>A). Moreover, T2D patients bearing the 1068 G>A SNP showed increased insulin levels and a better pancreatic ß-cell function (pâ¯<â¯0.05 in both cases) compared to patients with the wild type genotype. However, the HbA1c levels, fasting glucose levels and the degree of insulin resistance were similar in T2D patients carrying or not the G>A SNP. Our results suggest that although the 1068 G>A polymorphism of the P2RX7 gene is associated with an increased ß-cell function and IL-1Ra release in T2D patients, the glycemic control is not significantly affected by the presence of this SNP.
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Diabetes Mellitus Tipo 2/genética , Células Secretoras de Insulina/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/genética , Polimorfismo de Nucleotídeo Único , Receptores Purinérgicos P2X7/genética , Adulto , Glicemia/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Feminino , Expressão Gênica , Genótipo , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/patologia , Proteína Antagonista do Receptor de Interleucina 1/sangue , Masculino , Pessoa de Meia-Idade , Receptores Purinérgicos P2X7/sangueRESUMO
Dengue virus (DENV) and parvovirus B19 (B19V) infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL)-1 receptor antagonist (Ra), CXCL10/inducible protein-10 (IP-10), CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1) were determined by multiplex immunoassay in serum samples obtained from B19V (37) and DENV-infected (36) patients and from healthy individuals (7). Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1β, while CXCL10/IP-10 was confirmed as a strong pro-inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients.
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Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem , /sangue , /sangue , /sangue , Dengue/sangue , Proteína Antagonista do Receptor de Interleucina 1/sangue , Infecções por Parvoviridae/sangue , Doença Aguda , Biomarcadores/sangue , Estudos de Casos e Controles , /imunologia , /imunologia , /imunologia , Dengue/imunologia , Imunoensaio , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Estudos Prospectivos , Infecções por Parvoviridae/imunologiaRESUMO
OBJETIVO: avaliar a utilidade de citocinas pró-inflamatórias (TNF-±, IL-1² e IL-6) e de citocinas antinflamatórias (IL-10 e IL-1Ra) no diagnóstico da sepse neonatal, e verificar se a homeostase entre estes mediadores poderia ser determinante para a evolução clínica da doença. MÉTODO: coorte prospectiva compreendendo 31 recém-nascidos (RN) com diagnóstico de sepse neonatal, classificados em dois grupos: sepse e sepse grave, com evolução complicada (choque, falência múltipla de órgãos, óbito). Os níveis séricos de TNF-±; IL-1²; IL-6; IL-10 e IL-1Ra foram mensurados nos dias 0 (diagnóstico), 3 e 7 (evolutivos). Foram calculadas as médias, desvios-padrão, medianas, e valores mínimos e máximos para cada um dos mediadores. Foram construídos gráficos dos perfis individuais dos pacientes, e o perfil médio dos dois grupos contendo os erros-padrão. Para o tratamento estatístico dos dados oriundos da avaliação das concentrações de citocinas ao longo do tempo, foi utilizado o teste ANOVA com medidas repetidas. Para todas as análises realizadas foi adotado nível de significância de 5 por cento. RESULTADOS: no grupo de recém-nascidos com sepse e boa evolução, os níveis séricos de TNF-±; IL-1² e Il-10 se apresentaram próximos aos valores mínimos detectáveis pelo método, e nos RN com sepse grave, esses níveis foram estatisticamente superiores (p<0,01). As concentrações de IL-6 e IL-1Ra analisadas, de forma evolutiva (dias zero, 3 e 7 após o diagnóstico), revelaram níveis séricos sempre elevados e maiores na sepse grave em relação a sepse com boa evolução (p<0,01). A relação IL-6/IL-1Ra nos RN com sepse mostrou predomínio da ação pró-inflamatória no dia 0 (razão >1) e da resposta antiinflamatória nos dia 3 e 7 de evolução (razão <1), enquanto na sepse grave e evolução complicada, houve predomínio da ação pró-inflamatória no dia zero e no dia 3 (razão >1) e somente no dia 7, houve predomínio da ação antiinflamatória (razão <1). CONCLUSÕES: as concentrações ...(AU)
OBJECTIVES: to evaluate the utility of pro-inflammatory cytokines (TNF-±, IL1-², and IL- 6) and anti-inflammatory cytokines (IL-10 and IL-1Ra) for the diagnosis of neonatal sepsis, and to verify if the homeostasis of these mediators might determine the clinical outcome. METHOD: prospective cohort study including 31 newborns with neonatal sepsis whose diagnosis was made on the basis of clinical signs and positive blood culture, or high C-reactive protein. Newborns were classified in two groups: sepsis and favorable outcome, and severe sepsis with unfavorable outcome (septic shock and/or DIVC and/or FMOS and/or death). On days 0 (diagnosis), 3 and 7 after diagnosis, serum levels of TNF-±, IL-1², IL-6, IL-10, and IL-1Ra were measured. Statistical analysis included mean values, standard deviation, median, and minimum and maximum values of all mediators, as well as the construction of mean profiles for each patient and then for both groups (with standard errors). The ANOVA with repetitive measures was used to compare cytokines variation according to time. The significance level for all statistical analyses was 5 percent. RESULTS: the newborns who evolved favorably presented serum levels of TNF-±, IL-1² and IL-10 very close to the minimum levels detectable by the method, whilst in the newborns with severe sepsis, these cytokine levels were significantly higher (p<0.01). IL-6 and IL-1Ra serum levels were always high irrespective of the day analyzed, and even higher in the group with unfavorable outcome (p<0.01). IL-6/IL-1Ra ratio in the group with sepsis and favorable outcome showed predominance of antiinflammatory response (r >1) on day 0, and inversion on days 3 and 7. On the contrary, IL-6/IL- 1Ra ratio was >1 on day 0 and 3, and <1 only on day 7 in the group of sepsis and unfavorable outcome. CONCLUSIONS: the analyzed mediators were effective to diagnose neonatal sepsis, and also as predictive factors of disease severity, mainly with ...(AU)
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A hanseníase é uma doença infectocontagiosa espectral que acompanha-se por uma série de eventos imunológicos desencadeados pela resposta do hospedeiro frente ao agente etiológico, o Mycobacterium leprae. Evidências sugerem que a indução e manutenção da resposta imune/inflamatória na hanseníase estão vinculadas a interações de múltiplas células e fatores solúveis, particularmente através da ação de citocinas. Nesse estudo, foram mensurados níveis de IL-1β e IL-1Ra de 37 casos novos de hanseníase acompanhados ao longo do tratamento e 30 controles sadios pelo teste ELISA. A coleta de sangue periférico foi realizada em quatro tempos para os casos de hanseníase (pré-tratamento com PQT, 2ª dose, 6ª dose e pós-PQT) e em único momento para os controles. Na comparação dos níveis das moléculas de casos no pré-PQT e controles, houve diferença estatisticamente significativa somente para IL-1β. Nossos resultados sugerem a participação dessa citocina no processo imune/inflamatório.
Leprosy is an infectious and contagious spectral disease accompanied by a series of immunological events triggered by the host's response to the etiologic agent, Mycobacterium leprae. Evidence suggests that the induction and maintenance of the immune/inflammatory response in leprosy are linked to multiple cell interactions and soluble factors, mainly through the action of cytokines. The ELISA test was used to measure the levels of IL-1β and IL-1Ra in 37 new leprosy patients followed-up during treatment and 30 healthy controls. Peripheral blood was collected four times during the treatment of leprosy patients (MDT pretreatment, 2nd dose, 6th dose and post-MDT), and only once from the controls. The comparison of molecular levels in pre-MDT patients and controls showed a statistically significant difference for IL-1β. The results suggest the participation of this cytokine in the genesis of the immune/inflammatory process.