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1.
Cell Mol Immunol ; 17(10): 1092-1094, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32917983
3.
Front Immunol ; 11: 2160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983180

RESUMO

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading worldwide. Measuring the prevention and control of the disease has become a matter requiring urgent focus. Objective: Based on coronavirus disease 2019 (COVID-19) clinical data from Wuhan, we conducted an in-depth analysis to clarify some of the pathological mechanisms of the disease and identify simple measures to predict its severity early on. Methods: A total of 230 patients with non-mild COVID-19 were recruited, and information on their clinical characteristics, inflammatory cytokines, and T lymphocyte subsets was collected. Risk factors for severity were analyzed by binary logistic regression, and the associations of neutrophil-to-lymphocyte ratios (N/LRs) with illness severity, disease course, CT grading, inflammatory cytokines, and T lymphocyte subsets were evaluated. Results: Our results showed that the N/LRs were closely related to interleukin (IL)-6 and IL-10 (P < 0.001, P = 0.024) and to CD3+ and CD8+ T lymphocytes (P < 0.001, P = 0.046). In particular, the N/LRs were positively correlated with the severity and course of the disease (P = 0.021, P < 0.001). Compared to the values at the first test after admission, IL-6 and IL-10 were significantly decreased and increased, respectively, as of the last test before discharge (P = 0.006, P < 0.001). More importantly, through binary logistic regression, we found that male sex, underlying diseases (such as cardiovascular disease), pulse, and N/LRs were all closely related to the severity of the disease (P = 0.004, P = 0.012, P = 0.013, P = 0.028). Conclusions: As a quick and convenient marker of inflammation, N/LRs may predict the disease course and severity level of non-mild COVID-19; male sex, cardiovascular disease, and pulse are also risk factors for the severity of non-mild COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Índice de Gravidade de Doença , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Biomarcadores , Doenças Cardiovasculares , Infecções por Coronavirus/virologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Pulso Arterial , Fatores de Risco , Fatores Sexuais
4.
PLoS One ; 15(8): e0238160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822430

RESUMO

OBJECTIVE: Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers. METHODS: Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to the Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease. RESULTS: Cohorts with elevated levels of white blood cells (WBCs) (OR = 1.75), neutrophil count (OR = 2.62), D-dimer (OR = 3.97), prolonged prothrombin time (PT) (OR = 1.82), fibrinogen (OR = 3.14), erythrocyte sedimentation rate (OR = 1.60), procalcitonin (OR = 4.76), IL-6 (OR = 2.10), and IL-10 (OR = 4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity = 100%, specificity = 81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74x109/L for identifying patients at high risk of severe COVID-19. Likewise, ICU admission was associated with higher levels of WBCs (OR = 5.21), neutrophils (OR = 6.25), D-dimer (OR = 4.19), and prolonged PT (OR = 2.18). Patients with high IL-6 (OR = 13.87), CRP (OR = 7.09), D-dimer (OR = 6.36), and neutrophils (OR = 6.25) had the highest likelihood of mortality. CONCLUSIONS: Several hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Criança , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pró-Calcitonina/sangue , Prognóstico , Tempo de Protrombina , Adulto Jovem
5.
BMC Infect Dis ; 20(1): 553, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736606

RESUMO

BACKGROUND: We examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis. METHODS: We prospectively enrolled 1272 contacts of culture-confirmed pulmonary tuberculosis patients at 9 United States and Canadian sites. Epidemiologic characteristics were recorded. Blood was collected and stimulated with Mycobacterium tuberculosis culture filtrate protein, and tumor necrosis factor (TNF-α), interferon gamma (IFN-γ), and interleukin 10 (IL-10) concentrations were determined using immunoassays. RESULTS: Of 1272 contacts, 41 (3.2%) were diagnosed with tuberculosis before or < 30 days after blood collection (co-prevalent tuberculosis) and 19 (1.5%) during subsequent four-year follow-up (incident tuberculosis). Compared with contacts without tuberculosis, those with co-prevalent tuberculosis had higher median baseline TNF-α and IFN-γ concentrations (in pg/mL, TNF-α 129 versus 71, P < .01; IFN-γ 231 versus 27, P < .001), and those who subsequently developed incident tuberculosis had higher median baseline TNF-α concentrations (in pg/mL, 257 vs. 71, P < .05). In multivariate analysis, contact age < 15 years, US/Canadian birth, and IFN or TNF concentrations > the median were associated with co-prevalent tuberculosis (P < .01 for each); female sex (P = .03) and smoking (P < .01) were associated with incident tuberculosis. In algorithms combining young age, positive skin test results, and elevated CFPS TNF-α, IFN-γ, and IL-10 responses, the positive predictive values for co-prevalent and incident tuberculosis were 40 and 25%, respectively. CONCLUSIONS: Cytokine concentrations and epidemiologic factors at the time of contact investigation may predict co-prevalent and incident tuberculosis.


Assuntos
Interferon gama/sangue , Interleucina-10/sangue , Tuberculose/diagnóstico , Fator de Necrose Tumoral alfa/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Canadá/epidemiologia , Criança , Pré-Escolar , Busca de Comunicante , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tuberculose/sangue , Estados Unidos/epidemiologia , Adulto Jovem
6.
Mikrobiyol Bul ; 54(2): 266-278, 2020 Apr.
Artigo em Turco | MEDLINE | ID: mdl-32723282

RESUMO

Hepatitis B infection is still among the most important public health problems worldwide, even great improvements have been made in the treatment strategies. Hepatitis B virus (HBV) replicates itself by entering the liver cells and simultaneously with the antigen release, many antagonistic immune responses are induced by the regulatory cells including T cell (Treg), T helper 17 (Th17), T helper 1 (Th1) and T helper 2 (Th2) cells. The main function of Treg cells is to develop an appropriate immune response against infection and to suppress the immune response if it is not required. Tregs suppress the effector T cells via secreting immune system supressor cytokines such as Transforming Growth Factor-Beta and interleukin (IL)-10 or contact dependent way. Tregs protect cells from immunopathologic damage of HBV specific T cell immune response and also cause viral persistence, cirrhosis, hepatocellular carsinoma (HCC) and autoimmunity but the mechanisms are not clear, yet. In this study, we aimed to determine whether evaluation of Treg cells and cytokine IL-10 levels together in hepatitis B patients is useful that may indicate the disease survey and response to the treatment. The peripheral blood samples of ninety-one volunteers, including 61 HBV infected patients and 30 healthy controls selected from applicants of Infectious Diseases Outpatient/Clinic Service, were taken. Their CD4+CD25highFOXP3+CD152+CD127lowTreg cell distribution were measured by flow cytometry method, using the recently defined markers. The level of IL-10 cytokine released by immunomodulatory cells was determined by quantitative ELISA method. Treg cell percentages of the patients with acute hepatitis B were below the normal range (2-4%) (median= 1.50%, 0.6-3.5) and the difference was statistically significant (p= 0.005). Treg cell percentages of the patients with chronic hepatitis B were higher than the control group (p< 0.05), and it was found to be related to the parameters used in the diagnosis, staging and follow-up of the disease. IL-10 levels were significantly higher in all hepatitis B clinical stages compared to the healthy controls (median= 11.7, 17.3-44.9) (p< 0.05). Also, in parallel with Treg cells, IL-10 levels were correlated with HBV DNA load and HBsAg levels (r= 0.48, p< 0.02). Treg cells and the related cytokine IL-10 are thought to play an important role in the immunology of HBV infection and therefore, promising to follow up the disease and to develop new therapeutic strategies targeting the Treg cell.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Hepatite B , Interleucina-10 , Linfócitos T Reguladores , Hepatite B/sangue , Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica , Humanos , Interleucina-10/sangue , Neoplasias Hepáticas , Linfócitos T Reguladores/imunologia
7.
Emerg Microbes Infect ; 9(1): 1123-1130, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: covidwho-457402

RESUMO

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.


Assuntos
Infecções por Coronavirus/diagnóstico , Interleucina-10/sangue , Interleucina-6/sangue , Pneumonia Viral/diagnóstico , Betacoronavirus , Biomarcadores/sangue , Proteína C-Reativa/análise , China , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Estado Terminal , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Citocinas/sangue , Humanos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia
8.
BMC Neurol ; 20(1): 241, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532251

RESUMO

BACKGROUND: Increasing evidence supports the role of soluble inflammatory mediators in the pathogenesis of refractory temporal lobe epilepsy (TLE). Hippocampal sclerosis (HS) is a well-described pathohistological abnormality in TLE. The association of proinflammatory cytokines with epileptic disease profiles is well established; however, the potential significance of circulating interleukin 10 (IL-10), particularly in TLE-associated HS, is still poorly understood. Therefore, taking into consideration the neuroprotective and anticonvulsive effects of IL-10, we performed this study to examine the role of the plasma levels of IL-10 in patients with TLE with HS (TLE + HS), TLE without HS (TLE-HS) and with other types of epilepsy. METHODS: This study included 270 patients with refractory epilepsy who were classified into four groups: i) 34 patients with TLE + HS, ii) 105 patients with TLE-HS, iii) 95 patients with extra-TLE (XLE) and iv) 36 patients with idiopathic generalized epilepsy (IGE). The plasma IL-10 levels were quantified using a commercially available enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-10 levels were significantly lower in TLE + HS than in TLE-HS (p = 0.013). In a subgroup of TLE-HS patients who had seizures 1 month before sampling, patients with seizures had significantly higher IL-10 levels than patients who were seizure-free (p = 0.039). Among a small group (n = 15) of non-refractory TLE-HS patients, IL-10 levels showed a moderate negative correlation with the duration of epilepsy (r = - 0.585, p = 0.023). CONCLUSIONS: This study demonstrated that chronically reduced levels of plasma IL-10 were associated with HS in TLE patients, suggesting that there was an inadequate systemic anti-inflammatory immune response. These results could provide new biological insights into the pathophysiology of HS in TLE. We also found that the production of IL-10 could be affected by the seizure frequency and declined concomitantly with increased disease durations. Therefore, the measurement of plasma IL-10 may have diagnostic value as a biomarker for stratifying TLE + HS from other epilepsy types or as a marker of disease progression towards a progressive form of epilepsy.


Assuntos
Epilepsia do Lobo Temporal/sangue , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Interleucina-10/sangue , Adulto , Epilepsia Resistente a Medicamentos/sangue , Epilepsia Resistente a Medicamentos/imunologia , Epilepsia Resistente a Medicamentos/patologia , Epilepsia do Lobo Temporal/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose/sangue , Esclerose/complicações , Esclerose/patologia
9.
Emerg Microbes Infect ; 9(1): 1123-1130, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32475230

RESUMO

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.


Assuntos
Infecções por Coronavirus/diagnóstico , Interleucina-10/sangue , Interleucina-6/sangue , Pneumonia Viral/diagnóstico , Betacoronavirus , Biomarcadores/sangue , Proteína C-Reativa/análise , China , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Estado Terminal , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Citocinas/sangue , Humanos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia
10.
Clin Exp Immunol ; 201(1): 76-84, 2020 07.
Artigo em Inglês | MEDLINE | ID: covidwho-184034

RESUMO

Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Subunidade alfa de Receptor de Interleucina-2/sangue , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Linfócitos T/virologia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , Biomarcadores/sangue , Proteína C-Reativa/imunologia , Proteína C-Reativa/metabolismo , China/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Progressão da Doença , Feminino , Ferritinas/sangue , Ferritinas/imunologia , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Interleucina-8/sangue , Interleucina-8/imunologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pró-Calcitonina/sangue , Pró-Calcitonina/imunologia , Prognóstico , Índice de Gravidade de Doença , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
11.
Medicine (Baltimore) ; 99(18): e20044, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358386

RESUMO

Colorectal cancer (CRC) patients have been shown to express a cytokine signature that is detectable in serum and contributes to cancer pathogenesis. The objective of this study was to evaluate the potential clinical significance of preoperative circulating cytokine levels in CRC patients.The expression of serum B7-H1 and IL-10 was assessed by ELISA in 89 patients and 64 health volunteers. As a control marker, CEA serum levels were measured by electrochemical luminescence detection. The receiver operating characteristic (ROC) curve was used to analysis to demonstrate the potential diagnostic value of these biomarkers.The expression of serum B7-H1 was significantly increased in CRC patients (P = .001) and associated with the progression of TNM stage and a positive association with serum IL-10 levels was also evident. Furthermore, serum B7-H1 and IL-10 expression was not influenced by age, gender, tumor location, or mass, whereas a relationship existed with tumor metastasis and TNM stage. The serum levels of B7-H1 and IL-10 on the 7th postoperative day were significantly decreased compared with that of preoperative serum levels (P = .001, P = .003 respectively). The area under the ROC curves (AUC) for B7-H1 and IL-10 were 0.7063 and 0.5706, respectively. The optimal sensitivity and specificity of B7-H1 for discriminating between colon cancer patients and healthy controls were 85.21% and 56.43%, respectively, using a cut-off value of 3.46 ng/mL. However, the combined ROC analysis using B7-H1 and IL-10 revealed an AUC of 0.8791, with a sensitivity of 90.63% and a specificity of 75.18%.The outcomes of the present study demonstrate the clinical significance of serum B7-H1 and IL-10 concentrations. Combined detection of B7-H1 plus IL-10 showed significantly increased sensitivity and specificity for discriminating between colorectal cancer patients and healthy controls compared these markers detection individual. The measurement of B7-H1 or IL-10 in sera following surgery may provide an additional tool for assessing the curative effects of surgery in CRC patients.


Assuntos
Antígeno B7-H1/sangue , Neoplasias Colorretais/sangue , Interleucina-10/sangue , Idoso , Biomarcadores Tumorais , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Curva ROC , Sensibilidade e Especificidade
12.
PLoS Negl Trop Dis ; 14(5): e0008155, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32365058

RESUMO

Plasmodium vivax malaria is a neglected disease, particularly during pregnancy. Severe vivax malaria is associated with inflammatory responses but in pregnancy immune alterations make it uncertain as to what cytokine signatures predominate, and how the type and quantity of blood immune mediators influence delivery outcomes. We measured the plasma concentrations of a set of thirty-one biomarkers, comprising cytokines, chemokines and growth factors, in 987 plasma samples from a cohort of 572 pregnant women from five malaria-endemic tropical countries and related these concentrations to delivery outcomes (birth weight and hemoglobin levels) and malaria infection. Samples were collected at recruitment (first antenatal visit) and at delivery (periphery, cord and placenta). At recruitment, we found that P. vivax-infected pregnant women had higher plasma concentrations of proinflammatory (IL-6, IL-1ß, CCL4, CCL2, CXCL10) and TH1-related cytokines (mainly IL-12) than uninfected women. This biomarker signature was essentially lost at delivery and was not associated with birth weight nor hemoglobin levels. Antiinflammatory cytokines (IL-10) were positively associated with infection and poor delivery outcomes. CCL11 was the only biomarker to show a negative association with P. vivax infection and its concentration at recruitment was positively associated with hemoglobin levels at delivery. Birth weight was negatively associated with peripheral IL-4 levels at delivery. Our multi-biomarker multicenter study is the first comprehensive one to characterize the immunological signature of P. vivax infection in pregnancy thus far. In conclusion, data show that while TH1 and pro-inflammatory responses are dominant during P. vivax infection in pregnancy, antiinflammatory cytokines may compensate excessive inflammation avoiding poor delivery outcomes, and skewness toward a TH2 response may trigger worse delivery outcomes. CCL11, a chemokine largely neglected in the field of malaria, emerges as an important marker of exposure or mediator in this condition.


Assuntos
Citocinas/sangue , Malária Vivax/sangue , Plasmodium vivax/fisiologia , Complicações Parasitárias na Gravidez/sangue , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Interleucina-10/sangue , Interleucina-1beta/sangue , Malária Vivax/imunologia , Malária Vivax/parasitologia , Malária Vivax/fisiopatologia , Masculino , Gravidez , Complicações Parasitárias na Gravidez/imunologia , Complicações Parasitárias na Gravidez/parasitologia , Complicações Parasitárias na Gravidez/fisiopatologia , Resultado da Gravidez , Células Th2/imunologia , Adulto Jovem
13.
Pediatr Infect Dis J ; 39(7): e91-e94, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32384397

RESUMO

BACKGROUND: Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. METHODS: A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children's Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. RESULTS: Eight of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. CONCLUSIONS: More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Adolescente , Betacoronavirus/isolamento & purificação , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Tosse/virologia , Progressão da Doença , Feminino , Febre/virologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Interleucina-10/sangue , Interleucina-6/sangue , Contagem de Leucócitos , Masculino , Análise Multivariada , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
14.
Clin Exp Immunol ; 201(1): 76-84, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32365221

RESUMO

Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Subunidade alfa de Receptor de Interleucina-2/sangue , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Linfócitos T/virologia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , Biomarcadores/sangue , Proteína C-Reativa/imunologia , Proteína C-Reativa/metabolismo , China/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Progressão da Doença , Feminino , Ferritinas/sangue , Ferritinas/imunologia , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Interleucina-8/sangue , Interleucina-8/imunologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pró-Calcitonina/sangue , Pró-Calcitonina/imunologia , Prognóstico , Índice de Gravidade de Doença , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
15.
Pharmacol Res ; 159: 104946, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32450346

RESUMO

Coronavirus Disease 2019 (COVID-19) has sparked a global pandemic, affecting more than 4 million people worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute lung injury (ALI) and even acute respiratory distress syndrome (ARDS); with a fatality of 7.0 %. Accumulating evidence suggested that the progression of COVID-19 is associated with lymphopenia and excessive inflammation, and a subset of severe cases might exhibit cytokine storm triggered by secondary hemophagocytic lymphohistiocytosis (sHLH). Furthermore, secondary bacterial infection may contribute to the exacerbation of COVID-19. We recommend using both IL-10 and IL-6 as the indicators of cytokine storm, and monitoring the elevation of procalcitonin (PCT) as an alert for initiating antibacterial agents. Understanding the dynamic progression of SARS-CoV-2 infection is crucial to determine an effective treatment strategy to reduce the rising mortality of this global pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Pandemias , Pneumonia Viral/sangue , Biomarcadores/sangue , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/imunologia , Citocinas/sangue , Progressão da Doença , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Linfopenia/etiologia , Linfopenia/imunologia , Pneumonia Viral/etiologia , Pneumonia Viral/imunologia , Pró-Calcitonina/sangue
16.
PLoS One ; 15(4): e0231833, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298379

RESUMO

INTRODUCTION: Reflux promotes esophageal adenocarcinomas (EAC) creating a chronic inflammatory environment. EAC show an increasing incidence in the Western World and median survival rates are still low. The main reasons for poor prognosis despite new multimodal therapies are diagnosis of EACs at an already advanced stage and distant metastases. Hence, we wanted to investigate the presence of systemic inflammatory interleukins (IL) and their impact on patient prognosis. MATERIAL AND METHODS: Systemic expression levels of pro- and anti-inflammatory markers (IL-2, IL-4, IL-6, IL-10, IL-17A and IL-22) in the sera of 43 EAC patients without neoadjuvant radiochemotherapy were measured by flow cytometric analysis. A correlation to clinicopathological data was performed. Log-rank and Cox regression analysis were used to investigate the impact on patient survival. 43 sera of age and gender matched healthy volunteers were used as controls. RESULTS: Increased systemic IL-6 (p = 0.044) and lower IL-17A (p = 0.002) levels were found in EAC patients as opposed to controls. A correlation of IL-10 levels with an increased T stage was found (p = 0.020). Also, systemic IL-10 levels were highly elevated in patients with distant metastasis (p<0.001). However, only systemic IL-17A levels had an influence on patient survival in multivariate analysis. CONCLUSION: Systemic IL-6 levels are increased, while IL-17A levels are reduced in EAC patients compared to healthy controls. In addition, circulating IL-10 might help to identify patients with advanced disease and high IL-17A might indicate a limited prognosis.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/mortalidade , Interleucina-10/sangue , Interleucina-17/sangue , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/secundário , Feminino , Humanos , Interleucina-6/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estatísticas não Paramétricas
17.
BMC Infect Dis ; 20(1): 268, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32264832

RESUMO

BACKGROUND: Leptospirosis is a neglected zoonotic disease which is a major challenge for clinicians and public health professionals in tropical countries. The cytokine storm during the second (immune) phase is thought to be a major contributory factor for the leptospirosis disease severity. We aim to summarize evidence for cytokine response in leptospirosis at different clinical outcomes. METHODS: A systematic review was carried out to examine the cytokine response in leptospirosis patients using relevant scientific databases. Reference lists of the selected articles were also screened. Quality of the selected studies was assessed by using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: Of the 239 articles retrieved in the initial search, 18 studies fulfilled the selection criteria. India and Thailand have produced the highest number of studies (17% each, n = 3). The majority were comparative cross-sectional studies (72%, n = 13). Overall the quality of the selected studies was fair regardless of few drawbacks such as reporting of sample size and the lack of adjustment for confounders. Microscopic agglutination test (67% - 12/18) and enzyme-linked immunosorbent assay (50% - 9/18) were commonly used for the confirmation of leptospirosis and the measurement of cytokines respectively. IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10 and TNF-α levels were found to be significantly higher in severe than in mild leptospirosis. There were equivocal findings on the association between IL-1ß, TNF-α and IL-10/TNF-α ratio and disease severity. CONCLUSIONS: Leptospirosis had a wide-range of elevated cytokines. However, prospective studies in-relation to the onset of the symptom are required to better understand the pathophysiology of cytokine response in leptospirosis.


Assuntos
Interleucina-10/sangue , Interleucina-1beta/sangue , Leptospirose/sangue , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Adulto , Testes de Aglutinação , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Índia , Leptospirose/diagnóstico , Leptospirose/imunologia , Masculino , Pessoa de Meia-Idade , Tailândia
18.
Psychopharmacology (Berl) ; 237(6): 1861-1871, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32221694

RESUMO

AIM: To investigate whether circulating T cells including regulatory T cells (Treg) and derived cytokines contribute to the immune imbalance observed in schizophrenia. METHODS: Forty patients with schizophrenia and 40 age, sex, body mass index, education, and smoking status-matched healthy controls (HC) are included in the study. We stained cells with anti-CD14, anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-CD20, and anti-CD16/56. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with the human FoxP3 kit containing anti-CD4/anti-CD25 and intracellular anti-Foxp3. PBMCs were cultured for 72 h and stimulated with anti-CD3/anti-CD28. Cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17A) were measured from the culture supernatant and plasma using the Th1/Th2/Th17 cytokine bead array kit. RESULTS: In comparison with HC, Treg percentages in schizophrenia were higher (1.17 ± 0.63 vs 0.81 ± 0.53, P = 0.005) in unstimulated but lower in the stimulated condition (0.73 ± 0.69 vs 0.97 ± 0.55, P = 0.011). Activated T cell percentages were higher in schizophrenia than HC in unstimulated (2.22 ± 0.78 vs 1.64 ± 0.89, P = 0.001) and stimulated (2.25 ± 1.01 vs 1.72 ± 1.00, P = 0.010) conditions. The culture supernatant levels of IL-6 (7505.17 ± 5170.07 vs 1787.81 ± 1363.32, P < 0.001), IL-17A (191.73 ± 212.49 vs 46.43 ± 23.99, P < 0.001), TNF-α (1557 ± 1059.69 vs 426.57 ± 174.62, P = 0.023), and IFN-γ (3204.13 ± 1397.06 vs 447.79 ± 270.13, P < 0.001); and plasma levels of IL-6 (3.83 ± 3.41vs 1.89 ± 1.14, P = 0.003) and IL-17A (1.20 ± 0.84 vs 0.83 ± 0.53, P = 0.033) were higher in patients with schizophrenia than HC. CONCLUSION: Our explorative study shows reduced level of Foxp3 expressing Treg in a stimulated condition with induced levels of proinflammatory cytokines in patients with schizophrenia.


Assuntos
Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Esquizofrenia/sangue , Esquizofrenia/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Adulto , Estudos Transversais , Feminino , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-17/sangue , Interleucina-17/imunologia , Subunidade alfa de Receptor de Interleucina-2/sangue , Subunidade alfa de Receptor de Interleucina-2/imunologia , Masculino , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
19.
Am J Trop Med Hyg ; 102(5): 943-950, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32124729

RESUMO

Dengue is the most common mosquito-borne flaviviral infection in the world today. Several factors contribute and act synergistically to cause severe infection. One of these is dysregulated host immunological mediators that cause transient pathophysiology during infection. These mediators act on the endothelium to increase vascular permeability, which leads to plasma leakage compromising hemodynamics and coagulopathy. We conducted a prospective study to explore the expression of pro- and anti-inflammatory cytokines and how they relate to clinical dengue manifestations, by assessing their dynamics through acute dengue infection in adults admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. We performed cytokine analysis at three phases of infection for 96 hospitalized adults together with serotyping of confirmed dengue infection during the outbreaks of 2015 and 2016. The serum concentrations of seven cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha, and interferon gamma) were measured in duplicate using a commercial kit (Bio-Plex Human Cytokine Assay). In this study, the cytokine profile was suggestive of a T-helper 2 response. Most patients had secondary infection, and the levels of viremia were higher in patients with plasma leakage than those without plasma leakage. In addition, we observed that bleeding and hepatitis were associated with significantly higher levels of IL-8 during the early phases of infection. Furthermore, IL-6 levels in the early phase of infection were also elevated in bleeding patients with plasma leakage. These results suggest that IL-6 and IL-8 may act in synergy to cause bleeding in patients with plasma leakage.


Assuntos
Citocinas/metabolismo , Dengue/metabolismo , Hemorragia/etiologia , Hepatite Viral Humana/etiologia , Dengue Grave/metabolismo , Adulto , Citocinas/sangue , Dengue/complicações , Dengue/patologia , Feminino , Hemorragia/metabolismo , Hemorragia/virologia , Hepatite Viral Humana/metabolismo , Hepatite Viral Humana/virologia , Humanos , Interferon gama/sangue , Interferon gama/metabolismo , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-4/sangue , Interleucina-4/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Interleucina-8/sangue , Interleucina-8/metabolismo , Masculino , Estudos Prospectivos , Dengue Grave/complicações , Dengue Grave/patologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Carga Viral
20.
BMC Neurol ; 20(1): 85, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32151248

RESUMO

BACKGROUND: The search for noninvasive biomarkers of neuroinflammation and neurodegeneration has focused on various neurological disorders, including epilepsy. We sought to determine whether α-synuclein and cytokines are correlated with the degree of neuroinflammation and/or neurodegeneration in children with epilepsy and with acquired demyelinating disorders of the central nervous system (CNS), as a prototype of autoimmune neuroinflammatory disorders. METHODS: We analyzed serum and exosome levels of α-synuclein and serum proinflammatory and anti-inflammatory cytokines among 115 children with epilepsy and 10 acquired demyelinating disorders of the CNS and compared to 146 controls. Patients were enrolled prospectively and blood was obtained from patients within 48 h after acute afebrile seizure attacks or relapse of neurological symptoms. Acquired demyelinating disorders of the CNS include acute disseminated encephalomyelitis, multiple sclerosis, neuromyelitis optica spectrum disorders, and transverse myelitis. The controls were healthy age-matched children. The serum exosomes were extracted with ExoQuick exosome precipitation solution. Serum α-synuclein levels and serum levels of cytokines including IFN-ß, IFN-γ, IL-1ß, IL-6, IL-10 and TNF-α were measured using single and multiplex ELISA kits. Data were analyzed and compared with measures of disease severity, such as age at disease onset, duration of disease, and numbers of antiepileptic drug in use. RESULTS: Serum α-synuclein levels were significantly increased in patients with epilepsy and acquired demyelinating disorders of the CNS compared to controls (both, p < 0.05) and showed correlation with measures of disease severity both in epilepsy (p < 0.05, r = 0.2132) and in acquired demyelinating disorders of the CNS (p < 0.05, r = 0.5892). Exosome α-synuclein showed a significant correlation with serum α-synuclein (p < 0.0001, r = 0.5915). Serum IL-1ß levels were correlated only with the numbers of antiepileptic drug used in children with epilepsy (p < 0.001, r = 0.3428), suggesting drug resistant epilepsy. CONCLUSIONS: This is the first study in children demonstrating that serum α-synuclein levels were significantly increased in children with epilepsy and with acquired demyelinating disorders of the CNS and correlated with measures of disease severity. Serum IL-1ß levels showed significant correlation only with drug resistance in children with epilepsy. Thus, these data support that serum levels of α-synuclein and IL-1ß are potential prognostic biomarkers for disease severity in children with epilepsy. CNS, central nervous system.


Assuntos
Epilepsia/fisiopatologia , Interleucina-1beta/sangue , alfa-Sinucleína/sangue , Adolescente , Biomarcadores/sangue , Criança , Citocinas/sangue , Encefalomielite Aguda Disseminada/imunologia , Feminino , Humanos , Interleucina-10/sangue , Masculino , Esclerose Múltipla/imunologia , Neuromielite Óptica/sangue , Prognóstico , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangue
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