RESUMO
BACKGROUND: Micronutrients are known to modulate host immunity, and there is limited literature on this association in the context of dengue virus infection (DENV). METHODS: Using a nested case-control design in a surveillance program, we measured the following: anthropometry; nutritional biomarkers including serum ferritin, soluble transferrin receptor, retinol-binding protein (RBP), 25-hydroxy vitamin D, folate, and vitamin B12; and a panel of immune response markers. We then compared these measures across 4 illness categories: healthy control, nonfebrile DENV, other febrile illness (OFI), and apparent DENV using multivariate polytomous logistic regression models. RESULTS: Among 142 participants, serum ferritin (ng/mL) was associated with apparent DENV compared to healthy controls (odds ratio [OR], 2.66; confidence interval [CI], 1.53-4.62; P = .001), and RBP concentrations (µmol/L) were associated with apparent DENV (OR, 0.03; CI, 0.00-0.30; P = .003) and OFI (OR, 0.02; CI, 0.00-0.24; P = .003). In a subset of 71 participants, interleukin-15 levels (median fluorescent intensity) were positively associated with apparent DENV (OR, 1.09; CI, 1.03-1.14; P = .001) and negatively associated with nonfebrile DENV (OR, 0.89; CI, 0.80-0.99; P = .03) compared to healthy controls. CONCLUSIONS: After adjusting for the acute-phase response, serum ferritin and RBP concentrations were associated with apparent DENV and may represent biomarkers of clinical importance in the context of dengue illness.
Assuntos
Dengue/sangue , Dengue/imunologia , Interleucina-15/sangue , Vigilância da População , Adolescente , Biomarcadores/sangue , Índice de Massa Corporal , Tamanho Corporal , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Equador , Feminino , Ferritinas/sangue , Febre/sangue , Febre/virologia , Humanos , Masculino , Micronutrientes , Estado Nutricional , Orosomucoide/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Vitamina D/sangue , Adulto JovemRESUMO
This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes. Analysis of 30 immune mediators was carried out by multiplex or enzymatic immunoassays. Sustained virological response rate was 98.9%. Serum levels of cytokines were increased in HCV-infected patients when compared to control group. CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IL-1ß, IL-15, IFN-γ, IL-4, IL-10, TGF-ß, FGFb, and PAI-1 decreased significantly after antiviral therapy, reaching values similar to noninfected controls. TGF-ß and suPAR levels were associated with fibrosis/cirrhosis. Also, we observed amelioration in hepatic parameters after DAA treatment. Together, our results suggest that viral control induced by IFN-free DAA therapy restores inflammatory mediators in association with improvement in liver function.
Assuntos
Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Mediadores da Inflamação/sangue , Inflamação/imunologia , Sofosbuvir/uso terapêutico , Quimiocina CCL2/sangue , Citocinas/sangue , Hepatite C Crônica/sangue , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Interleucina-10/sangue , Interleucina-15/sangue , Interleucina-1beta/sangue , Interleucina-4/sangue , Inibidor 1 de Ativador de Plasminogênio/sangueRESUMO
IL-15 is part of the immune response in pulmonary tuberculosis (PTB) but amazingly, it may also induce physiological effects similar to those of insulin. We evaluated the IL-15 and insulin plasmatic levels in adults with PTB and with or without type 2 diabetes mellitus (DM2), who received previous antituberculosis therapy for at least 2 months. We analyzed the concentrations of glucose, glycated hemoglobin, insulin, as well as levels of IL-15, IL-2, IFN-γ, and TNF-α in patients with PTB, patients with PTB-DM2, household contacts with DM2 (C-DM2), and healthy household contacts (H-C). Our results showed unexpected high levels of glucose, insulin, and IL-15 in the PTB and C-DM2 groups. In comparison, low levels of these same indicators were observed in the PTB-DM2 and H-C groups. Interestingly, our analysis showed a positive correlation of IL-15 with insulin in the PTB group (râ¯=â¯0.73) and in the C-DM2 group (râ¯=â¯0.66). In comparison, a weak correlation between IL-15 and insulin was observed in the PTB-DM group (râ¯=â¯0.10) and in the H-C group (ρâ¯=â¯0.26). Our results suggest an association between IL-15 and insulin levels in the patient with PTB. Intriguingly, this association was weaker in the patient with PTB-DM2.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Insulina/sangue , Interleucina-15/sangue , Tuberculose Pulmonar/sangue , Adulto , Idoso , Antituberculosos/uso terapêutico , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
PURPOSE: We investigated the effects of 24 wk of combined training on proinflammatory and anti-inflammatory markers associated with obesity in obese middle-age men. METHODS: Thirty obese men (48.73 ± 1.04 yr; body mass index, 31.00 ± 0.29 kg·m) underwent 24 wk of combined training [CT (N = 17), aerobic (50%-85% of VËO2peak) and resistance (6-10 maximum repetition [RM]) training)] three times per week, 60 min per session, or a control group (N = 13). Anthropometric measures, maximal strength for leg press and bench press, peak oxygen uptake (VËO2peak) and serum concentrations of C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), IL-10, IL-15, resistin, leptin, and adiponectin were determined before (M1) and after 8 (M2), 16 (M3), and 24 (M4) wk of the experimental design. RESULTS: Significant increases were observed in the maximal strength for bench press and leg press, VËO2peak, and serum concentrations of adiponectin and IL-15 for CT. Concomitantly, significant decreases were observed in percentage body fat and serum concentrations of CRP, resistin, and leptin for CT after the experimental period. CONCLUSION: Twenty-four weeks of moderate- to high-intensity CT reduced markers of subclinical inflammation associated with obesity and improved insulin resistance and functional capabilities of obese middle-age men, regardless of dietary intervention and weight loss.
Assuntos
Terapia por Exercício/métodos , Inflamação/prevenção & controle , Obesidade/patologia , Obesidade/terapia , Adiponectina/sangue , Biomarcadores/sangue , Glicemia/metabolismo , Distribuição da Gordura Corporal , Proteína C-Reativa/metabolismo , Humanos , Resistência à Insulina , Interleucina-15/sangue , Perna (Membro)/fisiologia , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Obesidade/fisiopatologia , Consumo de Oxigênio , Aptidão Física , Treinamento Resistido , Resistina/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Epstein-Barr virus (EBV) plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV) on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC), group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3⺠cells, helper CD4⺠cells and CD19⺠B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ) and interleukin (IL)-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3⺠and CD4⺠cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL) compared to CHC patients (6.76 pg/mL) and normal controls (4.69 pg/mL). A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL) compared to EBV patients (29.3 pg/mL). Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.
Assuntos
Anticorpos Antivirais/sangue , Coinfecção/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Hepatite C Crônica/imunologia , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Doença Crônica , Coinfecção/virologia , DNA Viral/isolamento & purificação , Egito , Ensaio de Imunoadsorção Enzimática , Infecções por Vírus Epstein-Barr/complicações , Feminino , Citometria de Fluxo , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C Crônica/complicações , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Interferon gama/sangue , Interleucina-15/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Viral/isolamento & purificação , Adulto JovemRESUMO
During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3-) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3-, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease.