High levels of chemerin associated with variants in the NOS3 and APOB genes in rural populations of Ouro Preto, Minas Gerais, Brazil

Chemerin is an adipokine that has been associated with components of metabolic syndrome. It has been described to affect adipocyte metabolism and inflammatory responses in adipose tissue, as well as the systemic metabolism of lipids and glucose. Few epidemiological studies have evaluated classical and genetics cardiovascular risk factors (CVRFs) in the mixed adult rural population in Brazil. Therefore, the present study explored possible associations between CVRFs and chemerin. This cross-sectional study included 508 adults from the rural localities of Lavras Novas, Chapada, and Santo Antônio do Salto in Ouro Preto, Minas Gerais, Southeast Brazil. Demographic, behavioral, clinical, biochemical, anthropometric variables, and 12 single nucleotide polymorphisms (SNPs) linked with metabolic syndrome phenotypes were evaluated for associations with chemerin level. There was a significant association of high triglyceride levels [odds ratio (OR)=1.91, 95%CI: 1.23−2.98], insulin resistance (OR=1.82, 95%CI: 1.03−3.22), age (OR=1.64, 95%CI: 1.08−2.49), and sex (OR=1.99, 95%CI: 1.35−2.95) with high levels of chemerin. High chemerin levels were significantly associated with the genetic polymorphisms rs693 in the APOB gene (OR=1.50, 95%CI: 1.03−2.19) and rs1799983 in the NOS3 gene (OR=1.46, 95%CI: 1.01−2.12) for the AA and GT+TT genotypes, respectively. In the concomitant presence of genotypes AA of rs693 and GT+TT of rs1799983, the chance of presenting high levels of chemerin showed a 2.21-fold increase (95%CI: 1.25−3.88) compared to the reference genotype. The development of classical CVRFs in this population may be influenced by chemerin and by two risk genotypes characteristic of variants in well-studied genes for hypertension and dyslipidemia.

Inflammatory markers and occurrence of falls: Bambuí Cohort Study of Aging / Marcadores inflamatórios e ocorrência de quedas: coorte de idosos de Bambuí

ABSTRACT OBJECTIVE Analyze whether inflammatory markers are associated with falls among older adults living in Bambuí. METHODS Study that analyzed baseline data from a Bambuí Cohort Study of Aging, involving 1,250 participants. Data about falls were collected from previous 12 months, classified as single or multiple occurrence and severity (participant seeking health services). Information about sociodemographic characteristics, health behaviors and health condition was also collected and used as confounding factors. The exposures of interest included interleukins (IL-1β, IL-6, IL-8, IL-10, IL-12), tumor necrosis factor (TNF), ultra-sensitive C-reactive protein (us-CRP) and chemokines (CXCL9, CCL5, CCL10, MCP1). Data were processed through logistic regression, obtaining odds ratio and 95% confidence interval (95%CI). RESULTS The prevalence of falls was 27.1%; 40.1% of the older adults reported multiple falls and 33.3% sought health services. After adjustments, the following elevated levels were associated with falls: us-CRP (OR = 1.46, 95%CI 1.04-2.03), CCL5 (OR = 1.38, 95%CI 1.01-1.90) and CXCL9 (OR = 1.43, 95%CI 1.02-2.02). An association was observed between the number of elevated markers and the occurrence of falls: two (OR = 1.47, 95%CI 1.02-2.12) and three (OR = 2.08, 95%CI 1.12-3.87) elevated biomarkers indicated fall probability of 32.0% and 39.4%, respectively. CONCLUSIONS Elevated levels of us-CRP, CCL5 and CXCL9, which were associated with falls, may contribute to a proper understanding of the mechanism associated with the occurrence of falls among older people.

RESUMO OBJETIVO Analisar se marcadores inflamatórios estão associados a quedas em idosos vivendo na comunidade. MÉTODOS Estudo da coorte de idosos de Bambuí, envolvendo 1.250 participantes da linha de base do projeto. Foram coletadas informações sobre quedas nos últimos 12 meses, classificadas quanto à ocorrência (única ou múltipla) e gravidade (procura por serviços de saúde). O inquérito também continha informações a respeito das características sociodemográficas, comportamentais e condições de saúde, as quais foram utilizadas como fatores de confusão. As exposições pesquisadas incluíram: interleucinas (IL-1β, IL-6, IL-8, IL-10 e IL-12), fator de necrose tumoral (TNF), proteína C reativa ultrassensível (PCRus) e quimiocinas (CXCL9, CCL5, CCL10 e MCP1). O tratamento dos dados foi realizado por meio de regressão logística, obtendo-se odds ratio e intervalo de 95% de confiança (IC95%). RESULTADOS A prevalência de queda foi 27,1%; 40,1% dos idosos relataram quedas múltiplas e 33,3% procuraram serviços de saúde. Após ajustes, permaneceram associados às quedas os níveis elevados de PCRus (OR = 1,46; IC95% 1,04-2,03), CCL5 (OR = 1,38; IC95% 1,01-1,90) e CXCL9 (OR = 1,43; IC95% 1,02-2,02). Houve associação entre o número de marcadores elevados e a ocorrência de quedas: dois (OR = 1,47; IC95% 1,02-2,12) e três (OR = 2,08; IC95% 1,12-3,87) biomarcadores aumentados predisseram probabilidades de quedas iguais a 32,0% e 39,4%, respectivamente. CONCLUSÕES Os níveis elevados de PCRus, CCL5 e CXCL9, que estiveram associados a quedas, podem contribuir para o adequado entendimento do mecanismo associado à ocorrência desse evento em idosos.

Associação entre síndrome metabólica e marcadores inflamatórios em idosos residentes na comunidade / Asociación entre síndrome metabólico y marcadores inflamatorios en ancianos residentes en comunidades / Association of metabolic syndrome with inflammatory markers in a sample of community-dwelling older adults

O objetivo do trabalho foi identificar os pontos de corte dos marcadores inflamatórios que melhor discriminassem a ocorrência da síndrome metabólica entre idosos residentes na comunidade. Foram utilizados os dados da linha de base da coorte de idosos conduzida na cidade de Bambuí, Minas Gerais, Brasil. A exposição de interesse foi a presença da síndrome metabólica, definida pelo critério Adult Treatment Panel III, e os desfechos incluíram os seguintes marcadores inflamatórios: citocinas (IL-1β, IL-6, IL-10, IL-12 e TNF), quimiocinas (CXCL8, CXCL9, CCL2, CXCL10 e CCL5) e proteína C-reativa (PCR). A definição dos pontos de corte dos marcadores inflamatórios foi baseada no método Classification and Regression Tree (CART). As associações entre esses marcadores e a síndrome metabólica foram estimadas por modelos de regressão logística, obtendo-se odds ratio e intervalos de 95% de confiança (IC95%), considerando o ajustamento por fatores de confusão. A prevalência da síndrome metabólica foi de 49,1%, e os níveis de IL-1β, IL-12 e TNF não se mostraram associados a essa exposição. Após ajustamento, a presença da síndrome metabólica foi associada a maiores valores de IL-6 e PCR e a menores valores de CXCL8 e CCL5. Associações significativas ainda foram observadas com níveis séricos intermediários de CXCL9 e CXCL10. Além disso, a combinação dos marcadores apresentou associação significativa e consistente com a síndrome metabólica. Além de demonstrar associação entre síndrome metabólica e uma ampla gama de biomarcadores, alguns ainda não descritos na literatura, os resultados ressaltam que essa associação ocorre em níveis muito inferiores aos já demonstrados, sugerindo que a síndrome metabólica desempenha importante papel no perfil inflamatório dos idosos.

El objetivo del trabajo fue identificar los puntos de corte de los marcadores inflamatorios que mejor discriminaran la ocurrencia del síndrome metabólico entre ancianos residentes en comunidades. Se utilizaron datos de referencia de una cohorte de ancianos, realizada en la ciudad de Bambuí, Minas Gerais, Brasil. La exposición de interés fue la presencia del síndrome metabólico, definida por el criterio Adult Treatment Panel III, y los desenlaces incluyeron los siguientes marcadores inflamatorios: citocinas (IL-1β, IL-6, IL-10, IL-12 e TNF), quimiocinas (CXCL8, CXCL9, CCL2, CXCL10 y CCL5) y proteína C-reactiva (PCR). La definición de los puntos de corte de los marcadores inflamatorios se basó en el método Classification and Regression Tree (CART). Las asociaciones entre esos marcadores y el síndrome metabólico se estimaron mediante modelos de regresión logística, obteniéndose odds ratio e intervalos con 95% de confianza, considerando el ajuste por factores de confusión. La prevalencia del síndrome metabólico fue de 49,1%, y los niveles de IL-1β, IL12 y TNF no se mostraron asociados a esa exposición. Tras el ajuste, la presencia del síndrome metabólico se asoció a mayores valores de IL-6 y PCR y a menores valores de CXCL8 y CCL5. Las asociaciones significativas se observaron incluso con niveles séricos intermedios de CXCL9 y CXCL10. Asimismo, la combinación de los marcadores presentó una asociación significativa y consistente con el síndrome metabólico. Además de demostrar asociación entre el síndrome metabólico y una amplia gama de biomarcadores, algunos todavía no descritos en la literatura, los resultados resaltan que esa asociación ocurre en niveles muy inferiores a los ya demostrados, sugiriendo que el síndrome metabólico desempeña un importante papel en el perfil inflamatorio de los ancianos.

The study aimed to identify the cutoff points for inflammatory markers that best discriminate the occurrence of metabolic syndrome in community-dwelling older adults. Baseline data were used from the elderly cohort in the city of Bambuí, Minas Gerais State, Brazil. The target exposure was presence of metabolic syndrome, defined according to the Adult Treatment Panel III criterion, and the outcomes included the following inflammatory markers: cytokines (IL-1β, IL-6, IL-10, IL-12 e TNF), chemokines (CXCL8, CXCL9, CCL2, CXCL10, and CCL5), and C-reactive protein (CRP). Definition of the cutoff points for the inflammatory markers was based on the Classification and Regression Tree (CART) method. The associations between these markers and metabolic syndrome were estimated by logistic regression models, obtaining odds ratios and 95% confidence intervals, considering adjustment for confounding factors. Prevalence of metabolic syndrome was 49.1%, and IL-1β, IL-12, and TNF levels were not associated statistically with this exposure. After adjustment, presence of metabolic syndrome was associated with higher IL-6 and CRP levels and lower CXCL8 and CCL5. Significant associations were also observed with intermediate serum CXCL9 and CXCL10 levels. The combination of markers also showed a significant and consistent association with metabolic syndrome. In addition to demonstrating an association between metabolic syndrome and a wide range of biomarkers (some not previously described in the literature), the results highlight that this association occurs at much lower levels than previously demonstrated, suggesting that metabolic syndrome plays an important role in the inflammatory profile of the older adults.

Evaluation of Toll-like, chemokine, and integrin receptors on monocytes and neutrophils from peripheral blood of septic patients and their correlation with clinical outcomes

Recognition of pathogens is performed by specific receptors in cells of the innate immune system, which may undergo modulation during the continuum of clinical manifestations of sepsis. Monocytes and neutrophils play a key role in host defense by sensing and destroying microorganisms. This study aimed to evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell types of septic patients. Seventy-seven septic patients (SP) and 40 healthy volunteers (HV) were included in the study, and blood samples were collected on day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular receptors was carried out by flow cytometry. Expression of CD14 on monocytes and of CD11b and CXCR2 on neutrophils from SP was lower than that from HV. Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP compared with HV. Expression of TLR2 on the surface of neutrophils and that of TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition, SP who survived showed reduced expression of TLR2 and TLR4 on the surface of neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was higher at follow-up compared to baseline. We conclude that expression of recognition and cell signaling receptors is differentially regulated between SP and HV depending on the receptor being evaluated.

Soluble inflammatory markers as predictors of virological response in patients with chronic hepatitis C virus infection treated with interferon-α plus ribavirin

The host immune response plays an important role in viral clearance in patients who are chronically infected with hepatitis C virus (HCV) and are treated with interferon and ribavirin. Activation of the immune system involves the release of pro and anti-inflammatory molecules that can be measured in plasma samples. The present study aimed to evaluate the association between pretreatment plasma levels of chemokines and soluble tumor necrosis factor receptors (sTNF-R) and the virological response in treated patients with chronic hepatitis C infection. Forty-one chronically-infected HCV patients that were being treated with interferon-α (IFN-α) plus ribavirin were included in the study. Socio-demographic, clinical and laboratory data were collected and pretreatment plasma levels of chemokine CCL2, CCL3, CCL11, CCL24, chemokine CXCL9, CXCL10, sTNF-R1 and sTNF-R2 were measured. The virological response was assessed at treatment week 12, at the end of treatment and 24 weeks after treatment. Pretreatment CXCL10 levels were significantly higher in patients without an early virological response (EVR) or sustained virological response (SVR) compared to responders [512.9 pg/mL vs. 179.1 pg/mL (p = 0.011) and 289.9 pg/mL vs. 142.7 pg/mL (p = 0.045), respectively]. The accuracy of CXCL10 as a predictor of the absence of EVR and SVR was 0.79 [confidence interval (CI) 95 percent: 0.59-0.99] and 0.69 (CI 95 percent: 0.51-0.87), respectively. Pretreatment plasma levels of the other soluble inflammatory markers evaluated were not associated with a treatment response. Pretreatment CXCL10 levels were predictive of both EVR and SVR to IFN-α and ribavirin and may be useful in the evaluation of candidates for therapy.

Soluble inflammatory markers as predictors of hepatocellular damage and therapeutic response in chronic hepatitis C

Hepatitis C is an important burden worldwide being an important cause of cirrhosis and liver cancer in different parts of the world. Host immune response, especially T helper type 1 (Th1) cell-mediated, seems to play an important role in disease progression but is also crucial for viral elimination following specific therapy. Immune activation can be evaluated using peripheral levels of different cytokines, such as different chemokines (e.g. CCL5, CXCL10) and tumor necrosis factor alpha (TNF-á), and their soluble receptors (e.g. soluble TNF-á receptors 1 (sTNF-R1) and 2 (sTNF-R2). This review article focuses on the potential use of peripheral inflammatory markers as predictors of liver histological changes and therapeutic response among patients with chronic hepatitis C.