RESUMO
BACKGROUND: Arboviruses co-circulating within a population that are transmitted by the same vector have the potential to cause coinfections. Coinfections with dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) have been occurring in Brazil, but it is not well-understood how human responses vary during mono- or coinfections and whether they play different roles in pathogenesis. METHODS: We investigated the clinical, virological, and immunological status during patients' acute infections, focusing on the CCL/CXC chemokines, proinflammatory, as well as anti-inflammatory cytokines levels quantified by ELISAs. Viral load was determined by qRT-PCR in serum samples from 116 acute DENV, ZIKV, CHIKV, DENV/ZIKV, and CHIKV/ZIKV-infected adult patients from Brazil. RESULTS: Most of the acute patients displayed fever, headache, prostration, and myalgia, regardless of the type of arbovirus infection. Zika viral load was higher in CHIKV/ZIKV coinfected patients compared with ZIKV or DENV/ZIKV infections. All infected individuals presented increased concentrations of C-X-C motif chemokine ligand 10/interferon protein-10 (CXCL10/IP-10), C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1), and tumor necrosis factor alpha (TNF-α) compared to healthy donors. Interestingly, the ZIKV group separated from CHIKV/ZIKV due to higher levels of interleukin-10 (IL-10) and lower levels of TNF-α. While DENV/ZIKV differentiated from CHIKV due to their higher levels of CCL2/MCP-1, in CHIKV- and CHIKV/ZIKV-infected patients, levels of CXC10/IP-10, CCL2/MCP-1, and migration inhibitory factor (MIF) were associated with CHIKV viral load. By contrast, in DENV/ZIKV- and CHIKV/ZIKV-infected patients, levels of CXCL10/IP-10, CCL2/MCP-1, and TNF-α showed a significant inverse correlation with ZIKV viral load. CONCLUSIONS: From all the circulating mediators measured, we detected differences of IL-10, TNF-α, and CCL2/MCP-1 between arbovirus groups. We hypothesize that CXC10/IP-10, CCL2/MCP-1, and MIF in the CHIKV-infected group could regulate the CHIKV viral load, while CXC10/IP-10, CCL2/MCP-1, and TNF-α in DENV/ZIKV, and CHIKV/ZIKV groups, could regulate ZIKV viral load.
Assuntos
Febre de Chikungunya , Citocinas/sangue , Dengue , Infecção por Zika virus , Adulto , Brasil , Quimiocinas CC/sangue , Quimiocinas CXC/sangue , Febre de Chikungunya/imunologia , Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Coinfecção , Dengue/imunologia , Vírus da Dengue/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto Jovem , Zika virus/fisiologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologiaRESUMO
In this study, we investigated the correlation between serum chemokine (C-C motif) ligand 18 (CCL-18) and the prognosis as well as clinical characteristics of breast cancer. Blood samples from 207 breast cancer patients, 126 individuals with benign breast tumors, and 93 healthy women were collected. Serum CCL-18 expression was detected by enzyme-linked immunosorbent assay. Mann-Whitney's U tests were carried out to analyze the relationship between serum CCL-18 and clinicopathological variables. The Kaplan-Meier method was used to evaluate the overall survival (OS), whereas differences between groups were analyzed by log-rank tests. The COX proportional hazard regression model was used to determine the association between clinicopathological characteristics and survival. We found that serum CCL-18 was significantly higher in breast cancer patients (290.06 ± 89.52 pg/mL) as compared to that in individuals with benign tumors (170.14 ± 26.57 pg/mL) or healthy women (119.36 ± 38.77 pg/mL) (P < 0.05). Serum CCL-18 was correlated with clinical cancer stages (P = 0.007), and was associated with advanced cancer stage (P < 0.05). The 5-year OS rate of breast cancer patients with high serum CCL- 18 was 35.9% (HR = 3.908, 95%CI = 2.546-12.090, P < 0.05), which was significantly lower as compared to that for patients with low serum CCL-18 (85.5%). Based on our results, we conclude that CCL-18 is a prognostic biomarker in patients with advanced breast cancer in Chinese patients.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Carcinoma/sangue , Quimiocinas CC/sangue , Adulto , Neoplasias da Mama/patologia , Carcinoma/patologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
A defective chemokine motif in the HIV-1 Tat protein has been hypothesized to alter central nervous system cellular trafficking and inflammation, rendering HIV-1 subtype C less neuropathogenic than B. To evaluate this hypothesis, we compared biomarkers of cellular chemotaxis and inflammation in cerebrospinal fluid (CSF) and serum in individuals infected with HIV-1 subtypes B (n = 27) and C (n = 25) from Curitiba, Brazil. None had opportunistic infections. Chemokines (MCP-1, MIP-1α, MIP-1ß, RANTES, IP-10) and cytokines (TNF-α, IFN-γ, IL-1ß, IL-2, IL-4, IL-6, IL-7, IL-10) were measured using the multiplex bead suspension array immunoassays or ELISA HD. CSF and serum biomarker concentrations were compared between subtype B and C groups and HIV-positive and HIV-negative subjects (N = 19) using an independent group t test (unadjusted analysis) and linear regression (adjusted analysis), controlling for nadir CD4 and CSF and plasma HIV RNA suppression. CSF levels of cytokines and chemokines were significantly (p < 0.05) elevated in HIV-positive versus HIV-negative participants for 7/13 biomarkers measured, but levels did not differ for subtypes B and C. Serum levels were significantly elevated for 4/13 markers, with no significant differences between subtypes B and C. Although pleocytosis was much more frequent in HIV-positive than in HIV-negative individuals (27 vs. 0 %), subtypes B and C did not differ (32 and 22 %; p = 0.23). We did not find molecular evidence to support the hypothesis that intrathecal chemotaxis and inflammation is less in HIV-1 subtype C than in subtype B. Biomarker changes in CSF were more robust than in serum, suggesting compartmentalization of the immunological response to HIV.
Assuntos
Quimiocinas CC/líquido cefalorraquidiano , Quimiotaxia/imunologia , Infecções por HIV/líquido cefalorraquidiano , Interferon gama/líquido cefalorraquidiano , Interleucinas/líquido cefalorraquidiano , Leucocitose/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Adulto , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Estudos de Casos e Controles , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/virologia , Quimiocinas CC/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Interferon gama/sangue , Interleucinas/sangue , Leucocitose/sangue , Leucocitose/imunologia , Leucocitose/virologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , RNA Viral/imunologia , Fator de Necrose Tumoral alfa/sangue , Carga Viral/imunologiaAssuntos
Envelhecimento , Quimiocinas CC/sangue , Esquizofrenia/sangue , Adulto , Quimiocina CCL26 , Doença Crônica , Feminino , Humanos , Masculino , Adulto JovemRESUMO
The role of Th2 cytokines and Th2-associated chemokines in tuberculosis (TB) remains controversial, though in Mexico a polymorphism causing increased production of CCL2 is a risk factor. We studied levels of the Th2-associated chemokines CCL2 and CCL18, circulating soluble IL-4 receptors (sIL-4R), IL-4 and the inhibitory splice variant of IL-4 (IL-4δ2) in a cohort of patients with pulmonary TB and their healthy contacts. These were followed for 2 years during which time 10 contacts developed pulmonary TB. Results were compared with measurements made in renal and meningeal TB, and in disease controls with bacterial pneumonias or Dengue fever that have large Th2 components. In these disease controls both chemokines were significantly raised. They were also very significantly raised in all forms of TB, irrespective of age or disease site. Levels of CCL18 were raised least in meningeal TB, and most in pulmonary patients with long histories, when levels were similar to those in disease controls. Levels of CCL2, although also raised in all three forms of TB, were negatively correlated with CCL18. We found that levels of sIL-4R were strikingly reduced in all forms of TB, particularly meningeal. Contacts who progressed could not be distinguished from contacts who remained healthy at 2 years in terms of IL-4, sIL-4R, CCL2 or CCL18. However contacts had raised expression of IL-4δ2 as previously found. These results indicate vigorous and previously unrecorded activity within the Th2 axis, and further investigation is warranted.
Assuntos
Quimiocinas/sangue , Receptores de Interleucina-4/sangue , Tuberculose/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiocina CCL2/sangue , Quimiocinas CC/sangue , Criança , Pré-Escolar , Progressão da Doença , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Seguimentos , Humanos , Interleucina-4/sangue , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/imunologia , Tuberculose Meníngea/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/transmissão , Tuberculose Renal/imunologia , Adulto JovemRESUMO
BACKGROUND: Asthma is characterized by chronic inflammation of the airways with significant changes in leucocyte trafficking, cellular activation and tissue remodelling. Brain-derived neurotrophic factor (BDNF) has been involved with asthma and allergic diseases but its role as a severity marker in paediatric asthma has not been clinically assessed. OBJECTIVES: To evaluate plasma BDNF and inflammatory markers in order to address their relationships with disease severity in children (6-15 years) with controlled persistent asthma. METHODS: Children with persistent asthma were selected and lung function and skin prick tests were performed in all patients. Plasma BDNF levels and various inflammatory markers (CCL3, CCL11, CCL22, CCL24, CXCL8, CXCL9, CXCL10, soluble TNF receptors) were assessed by ELISAs. RESULTS: Subjects with moderate and severe asthma had higher BDNF levels than mild asthma and controls (P<0.001). The chemokines studied and soluble TNF receptors did not differ between the studied groups. CONCLUSION AND CLINICAL RELEVANCE: Our results indicate BDNF as a potential biomarker for clinical severity in children with asthma.
Assuntos
Asma/sangue , Asma/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Índice de Gravidade de Doença , Adolescente , Biomarcadores/sangue , Quimiocinas CC/sangue , Criança , Humanos , Receptores do Fator de Necrose Tumoral/sangueRESUMO
The pathophysiology of bipolar disorder (BD) includes, among other processes, changes in the neuroplasticity and regulation of apoptosis, which could potentially be influenced by inflammatory mediators such as chemokines. The objectives of this study were to investigate serum chemokine levels in patients with BD and to compare results with those obtained with healthy subjects. Here, serum chemokine levels of 30 euthymic patients with BD type I and 30 healthy volunteers were investigated and compared. The chemokines assessed were CCL2, CCL3, CCL8, CCL 9, CCL10, CCL11, and CCL24. Patients with BD showed significant differences in chemokine levels when compared with healthy subjects. While serum levels of CXCL10 were increased (p=.018), CCL24 levels were lower in bipolar patients (p=.025) when compared with controls. There was no statistical difference in the serum levels of CCL2, CCL3, CCL24, CXCL9, and CXCL11 between patients and controls. The presence of chemokine abnormalities in patients with BD during euthymia suggests that these inflammatory mediators should be further investigated with regard to their potential role as longstanding markers of the disorder.
Assuntos
Transtorno Bipolar/sangue , Quimiocinas CC/sangue , Quimiocinas CXC/sangue , Adulto , Análise de Variância , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Escalas de Graduação PsiquiátricaRESUMO
Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.
Assuntos
Periodontite Crônica/sangue , Mediadores da Inflamação/sangue , Biomarcadores/sangue , Quimiocina CCL2/sangue , Quimiocina CCL3/sangue , Quimiocina CCL4/sangue , Quimiocina CCL5/sangue , Quimiocina CXCL9/sangue , Quimiocinas CC/sangue , Citocinas/sangue , Proteína Ligante Fas/sangue , Fator 2 de Crescimento de Fibroblastos/sangue , Hemorragia Gengival/sangue , Fator Estimulador de Colônias de Granulócitos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Humanos , Interferon gama/sangue , Interleucina-9/sangue , Interleucinas/sangue , Linfotoxina-alfa/sangue , Perda da Inserção Periodontal/sangue , Bolsa Periodontal/sangue , Fator de Crescimento Transformador beta/sangueRESUMO
Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.
Avanços no diagnóstico da doença periodontal levam a métodos nos quais o risco e atividade da doença periodontal podem ser identificados e quantificados por biomarcadores. Pacientes com periodontite podem apresentar elevados níveis circulatórios de marcadores inflamatórios específicos que podem ser correlacionados com a severidade da doença. Portanto, o objetivo desse estudo foi avaliar as diferenças nos níveis séricos de biomarcadores inflamatórios em pacientes saudáveis e com doença periodontal. Foram incluídos no estudo 25 pacientes (8 saudáveis e 17 com periodontite crônica). Uma amostra de 15 mL de sangue foi obtida para identificar os marcadores inflamatórios simultaneamente utilizando Array de proteínas através de citometria de fluxo. De 24 citocinas inflamatórias analisadas, apenas 3 (RANTES, MIG e Eotaxina) apresentaram diferenças estatisticamente significantes (p<0,05) entre os dois grupos. Conclui-se que alguns marcadores inflamatórios selecionados apresentam diferença de concentração em pacientes com periodontite e saudáveis. A análise do perfil de citocinas pode ser utilizada tanto para distinguir pacientes periodontais de pacientes saudáveis, como para medir o risco à doença. Contudo, mais estudos com número maior de amostras são necessários para validar os achados sobre os biomarcadores específicos.
Assuntos
Humanos , Periodontite Crônica/sangue , Mediadores da Inflamação/sangue , Biomarcadores/sangue , /sangue , /sangue , /sangue , /sangue , Quimiocina CXCL9/sangue , Quimiocinas CC/sangue , Citocinas/sangue , Proteína Ligante Fas/sangue , /sangue , Hemorragia Gengival/sangue , Fator Estimulador de Colônias de Granulócitos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Interferon gama/sangue , Interleucina-9/sangue , Interleucinas/sangue , Linfotoxina-alfa/sangue , Perda da Inserção Periodontal/sangue , Bolsa Periodontal/sangue , Fator de Crescimento Transformador beta/sangueRESUMO
Diagnosis of leprosy is usually made clinically and there are no tests available for the routine laboratory diagnosis of the disease. The aim of this study was to investigate the potential role of chemokines as biologic markers of disease activity. We used an enzyme-linked immunosorbent assay to measure chemokines in plasma of patients with leprosy (LE) and non-infected (NI) individuals. There were significantly greater concentrations of the chemokines CCL3 and CCL11 in plasma of LE patients than in NI individuals. When the use of CCL11 to differentiate LE patients versus NI individuals was evaluated, the area under the receiver-operator-characteristic curve was 0.95 +/- 0.03 (P < 0.0001). In a group of selected individuals, CCL11 was useful in diagnosis of leprosy, thereby suggesting that measurement of this chemokine may be useful as an aid in diagnosing leprosis.