RESUMO
The pathogenic roles of Interleukine-16 (IL-16), CCL27, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and B-cell activating factor (BAFF) has been shown in some autoimmune and inflammatory diseases. We aimed to correlate the circulatory changes of such factors with the severity of disease in patients with multiple sclerosis (MS). This case-control study was conducted on 84 MS patients and 83 healthy controls. We measured the serum levels of IL-16, CCL27, TRAIL, and BAFF in all participants by enzyme-linked immune sorbent assay. Using the expanded disability status scale (EDSS), we evaluated the severity of MS. Finally, we assessed the correlation between serum levels of such factors with the severity of MS. We found increased serum levels of CCL27, IL-16, and BAFF in patients with MS compared to those in healthy subjects. However, no difference was found in serum levels of TRAIL between the patients and controls. In addition, a significant positive correlation between serum levels of CCL27, IL-16, TRAIL, and BAFF with disease severity according to EDSS score was determined. We showed higher serum levels of CCL27, BAFF, TRAIL, and IL-16 in MS patients with more severe disabilities than mild forms. Such finding may represent their contribution to the pathogenesis of MS. Blocking such molecules may yield new treatments for MS.
Assuntos
Fator Ativador de Células B , Quimiocina CCL27 , Interleucina-16 , Esclerose Múltipla , Ligante Indutor de Apoptose Relacionado a TNF , Fator Ativador de Células B/sangue , Estudos de Casos e Controles , Quimiocina CCL27/sangue , Humanos , Interleucina-16/sangue , Ligantes , Esclerose Múltipla/diagnóstico , Índice de Gravidade de Doença , Ligante Indutor de Apoptose Relacionado a TNF/sangueRESUMO
High-altitude polycythemia (HAPC) is a common aspect of chronic mountain sickness (CMS) caused by hypoxia and is the main cause of other symptoms associated with CMS. However, its pathogenesis and the mechanisms of high-altitude acclimation have not been fully elucidated. Exposure to high altitude is associated with elevated inflammatory mediators. In this study, the subjects were recruited and placed into a plain control (PC) group, plateau control (PUC) group, early HAPC (eHAPC) group, or a confirmed HAPC (cHAPC) group. Serum samples were collected, and inflammatory factors were measured by a novel antibody array methodology. The serum levels of interleukin-2 (IL-2), interleukin-3 (IL-3), and macrophage chemoattractant protein-1 (MCP-1) in the eHAPC group and the levels of interleukin-1 beta (IL-1 beta), IL-2, IL-3, tumor necrosis factor-alpha (TNF-alpha), MCP-1, and interleukin-16 (IL-16) in the cHAPC group were higher than those in the PUC group. More interestingly, the expression of IL-1 beta, IL-2, IL-3, TNF-alpha, MCP-1, and IL-16 in the PUC group showed a remarkable lower value than that in the PC group. These results suggest that these six factors might be involved in the pathogenesis of HAPC as well as acclimation to high altitudes. Altered inflammatory factors might be new biomarkers for HAPC and for high-altitude acclimation.
Assuntos
Doença da Altitude/genética , Altitude , Quimiocina CCL2/sangue , Interleucina-16/sangue , Interleucina-2/sangue , Interleucina-3/sangue , Policitemia/sangue , Policitemia/genética , Fator de Necrose Tumoral alfa/sangue , Aclimatação , Adulto , Doença da Altitude/sangue , Biomarcadores/sangue , Citocinas/sangue , Citocinas/metabolismo , Feminino , Humanos , Hipóxia , Inflamação , Masculino , Estresse OxidativoRESUMO
Periodontitis (PD) is a chronic inflammatory process resulting from the relationship of the immune response with the components in dental plaque. Cytokines and their genetic polymorphisms seem to be involved in the immunopathogenesis of this disease. This study aimed to evaluate the correlation of IL16 polymorphism with PD. A case-control study was conducted in a sample of individuals from southern Brazil. The genotyping of IL16, rs11556218 T>G, rs4072111 C>T e rs4778889 T>C, was performed using the PCR-RFLP methodology. The serum level of IL-16 was determined using an IL-16 ELISA kit for humans. SNPStats and OpenEpi software and Wilcoxon's U test were used to perform statistical analysis. IL16 rs11556218 polymorphism was significantly associated to PD in nonsmoking patients: individuals with G/G genotype were less likely to develop PD compared to the T/T genotype (OR = 0.10; Pc = 0.019, codominant model). In addition, the TTT haplotype was associated with a high risk for PD (OR = 2.45; P = 0.01). A low IL-16 serum level was observed among individuals with PD when compared to controls (P = 0.027). Thus, the IL16 rs16556218 polymorphism and the serum levels of IL-16 were associated with periodontitis in a Brazilian sample, and this was influenced by environmental factors such as smoking.
Assuntos
Predisposição Genética para Doença , Interleucina-16/genética , Periodontite/genética , Fumar/epidemiologia , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Genótipo , Técnicas de Genotipagem , Haplótipos , Humanos , Interleucina-16/sangue , Masculino , Pessoa de Meia-Idade , Periodontite/sangue , Periodontite/epidemiologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumar/efeitos adversosRESUMO
Adult primary immune thrombocytopenia (ITP) is an autoimmune-mediated haemorrhagic disorder. Interleukin-16 (IL-16) can directly affect cellular or humoural immunity by mediating the cellular cross-talk among T cells, B cells and dendritic cells. Several studies have focused on IL-16 as an immunomodulatory cytokine that takes part in Th1 polarization in autoimmune diseases. In this study, we investigated IL-16 expression in the bone marrow supernatant and plasma of ITP patients and healthy controls. What's more, we detected IL-16 expression in ITP patients with the single-agent 4-day high-dose dexamethasone (HD-DXM) therapy. In patients with active ITP, bone marrow supernatant and plasma IL-16 levels increased (P < 0.05) compared with those of healthy controls. In the meantime, the mRNA expression in BMMCs (pro-IL-16, caspase-3) and PBMCs (pro-IL-16, caspase-3 and T-bet) of ITP patients was increased (P < 0.05) relative to those of healthy controls. In patients who responded to HD-DXM therapy, both plasma IL-16 levels and gene expression in PBMCs (pro-IL-16, caspase-3, and T-bet) were decreased (P < 0.05). In summary, the abnormal level of IL-16 plays important roles in the pathogenesis of ITP. Regulating Th1 polarization associated with IL-16 by HD-DXM therapy may provide a novel insight for immune modulation in ITP.
Assuntos
Dexametasona/farmacologia , Imunossupressores/uso terapêutico , Interleucina-16/biossíntese , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adulto , Medula Óssea/metabolismo , Estudos de Casos e Controles , Caspase 3/biossíntese , Caspase 3/genética , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imunossupressores/administração & dosagem , Interleucina-16/sangue , Interleucina-16/genética , Interleucina-16/fisiologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/metabolismo , RNA Mensageiro/biossíntese , Proteínas com Domínio T/biossíntese , Proteínas com Domínio T/genética , Células Th1/imunologia , Doadores de Tecidos , Adulto JovemRESUMO
The natural course of acute Hepatitis C Virus (aHCV) infection is highly heterogeneous, and only few biomarkers have been identified to reliably predict the outcome of infection. We analysed a large panel of soluble inflammatory mediators, immune cell frequencies and phenotypes using peripheral blood samples from 26 patients with symptomatic aHCV infection from a controlled randomized clinical trial (ISRCTN88729946, www.isrctn.com). We found that patients with a spontaneous early HCV control demonstrated a distinct expression pattern of various soluble immune mediators including IFNα and IL-16. Immune cell phenotype and frequency differed between patients who cleared the viral infection early (n=13) and those who remained HCV RNA positive after 12 weeks of observation (n=13) with a reduced ratio of CD4+ T cells to NK cells in the non-early clearer. Further, correlation analyses of 50 cytokines and chemokines revealed more positive correlations in between the distinct cytokines, especially for IFNα and IL-16, and between the cytokines and HCV RNA levels in spontaneous early clearer patients. Beyond that, in vitro stimulation of CD4+ T cells with IL-16 reduced the susceptibility of these cells to killing by IFNα-activated NK cells. These data indicate that the immune cell composition and cytokine pattern varies considerably in patients with symptomatic aHCV infection. NK cell-mediated killing of CD4+ T cells might affect early control of HCV infection.
Assuntos
Linfócitos T CD4-Positivos/patologia , Hepatite C/sangue , Mediadores da Inflamação/sangue , Células Matadoras Naturais/patologia , Adulto , Biomarcadores/sangue , Linfócitos T CD4-Positivos/imunologia , Citotoxicidade Imunológica , Feminino , Hepacivirus/genética , Hepacivirus/fisiologia , Humanos , Interferon-alfa/sangue , Interleucina-16/sangue , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemAssuntos
Artrite Juvenil/complicações , Imunoglobulinas Intravenosas , Infliximab , Interferon gama/sangue , Interleucina-18/sangue , Síndrome de Ativação Macrofágica , Antirreumáticos/administração & dosagem , Antirreumáticos/imunologia , Pré-Escolar , Monitoramento de Medicamentos/métodos , Ferritinas/sangue , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/imunologia , Infliximab/administração & dosagem , Infliximab/imunologia , Interleucina-16/sangue , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/tratamento farmacológico , Síndrome de Ativação Macrofágica/etiologia , Síndrome de Ativação Macrofágica/imunologia , Prevenção Secundária/métodos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND/AIMS: Obesity is associated with chronic inflammation and cognitive decline, and is considered a major risk factor for neurodegeneration. Meanwhile, neuroinflammation is important in the pathogenesis and progression of neurodegenerative diseases. METHODS: In this study, we tested the hypothesis that donepezil would attenuate central inflammation and oxidative damage and improve memory deficit in high-fat diet (HFD)-fed mice. After 16 weeks on a HFD, C57BL/6J mice were given either donepezil (3 mg/kg, i.p.) or saline for 4 weeks in parallel to a control diet (CD) group. Thereafter, the step-through test was used to assess learning and memory function. RESULTS: In the brain of HFD-fed mice, levels of the proinflammatory cytokines interleukin 16 and tumor necrosis factor α were reduced by donepezil treatment. Similarly, HFD-induced protein levels of advanced glycation end-products and oxidative stress in the brain were significantly decreased by donepezil treatment. CONCLUSION: Our results indicate that donepezil may reverse obesity-related central inflammation and oxidative damage and improve memory deficit in HFD-fed mice.
Assuntos
Donepezila/uso terapêutico , Inflamação/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Nootrópicos/uso terapêutico , Obesidade/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Produtos Finais de Glicação Avançada/sangue , Inflamação/metabolismo , Resistência à Insulina , Interleucina-16/sangue , Aprendizagem , Masculino , Memória , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: There is growing evidence that history of allergic or autoimmune disease is associated with reduced risk of glioma, but few prospective studies have explored the biological basis. To assess associations with immune conditions and levels of 14 cytokines in serial prediagnostic serum samples, we conducted a study of glioma/brain cancer nested in a cohort of active component military personnel. METHODS: A total of 457 case-control sets were ascertained from the Department of Defense (DoD) Automated Central Tumour Registry, Defense Medical Surveillance System (DMSS) database, and DoD Serum Repository. These were individually matched on sex, race/ethnicity, birth year, number of serum samples (1, 2 or 3), and date(s) of sample collection. We obtained diagnoses of pre-existing immune-related conditions from the DMSS database and measured cytokines using Meso Scale Discovery assays. Statistical analyses included conditional logistic regression. RESULTS: Overall association between glioma and prior immune-related conditions was null. Higher levels of IL-15 and IL-16 were independently associated with lower glioma risks (Ptrend = 0.002 and Ptrend = 0.001); both associations were more pronounced in individuals with prior immune conditions (Pheterogeneity = 0.0009 and Pheterogeneity = 0.031). CONCLUSIONS: Associations with pre-diagnostic levels of IL-15 and IL-16 and their modification by diagnosis of immune-related conditions support the importance of immune alterations in glioma aetiology years before diagnosis.
Assuntos
Neoplasias Encefálicas/epidemiologia , Glioma/epidemiologia , Interleucina-15/sangue , Interleucina-16/sangue , Militares , Adulto , Distribuição por Idade , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/imunologia , Estudos de Casos e Controles , Feminino , Glioma/sangue , Glioma/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Sexually transmitted infections and chronic inflammation have been associated with an increased risk of prostate cancer. Inflammatory mediators, such as cytokines and free radicals, have been hypothesized to play a role. METHODS: To explore the role of inflammation in prostate cancer risk further, we examined the association between pre-diagnostic serum levels of interleukin-16 (IL-16), an important pleiotropic cytokine, and prostate cancer risk among 932 Caucasian cases and 942 controls and 154 African-American cases and 302 controls in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum IL-16 was quantified using enzyme-linked immunoassay. Logistic regression was used to estimate associations between IL-16 and prostate cancer risk, separately by race. RESULTS: Although no association between IL-16 and prostate cancer overall was observed among Caucasians (p = 0.27), a significantly increased risk of high-grade prostate cancer, defined as Gleason ≥ 7 (phet = 0.02), was observed with increasing levels of IL-16 (OR3rd vs. 1st tertile = 1.37, 95% CI 1.04-1.81, ptrend = 0.02). We also discovered a significant interaction between IL-16 and history of gonorrhea (p = 0.04). Among Caucasian men with a history of gonorrhea, elevated IL-16 levels were associated with an increased risk of prostate cancer (OR3rd vs. 1st tertile = 3.64, 95% CI 1.14-11.6) but no association was seen among those without a history of gonorrhea (OR3rd vs. 1st tertile = 1.06, 95% CI 0.83-1.34). No associations were observed among African-Americans. CONCLUSIONS: This study found evidence that higher pre-diagnostic IL-16 levels may be associated with increased risk of high-grade disease, supporting inflammation as potential mechanism by which sexually transmitted diseases may increase risk.
Assuntos
Inflamação/sangue , Interleucina-16/sangue , Neoplasias da Próstata/sangue , Negro ou Afro-Americano , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Estudos Prospectivos , Fatores de Risco , População BrancaRESUMO
Interleukin (IL)-16, a polypeptide cytokine, plays a crucial role in the inflammatory process, acting as a chemoattractant for peripheral immune cells and has been linked to various inflammatory diseases. However, its role in patients with acute myocardial infarction (AMI) is unclear.We retrospectively analyzed serum levels of IL-16 in blood of patients with (STEMI, nâ=â45) and without ST-segment elevation myocardial infarction (NSTEMI, nâ=â42) compared with controls with excluded coronary artery disease (nâ=â55). Furthermore, correlation analysis with inflammatory cells, C-reactive protein (CRP) levels, dendritic cell precursors (DCPs), and other clinical and biochemical markers was performed.Compared with controls, patients with STEMI and NSTEMI evidenced higher levels of IL-16 in pg/mL (STEMI: 759.38â±â471.54, NSTEMI: 677.77â±â438.8, control: 500.45â±â432.21; Pâ=â.002). IL-16 correlated with CRP (râ=â0.26, Pâ=â.001), leucocytes (râ=â0.38, Pâ<â.001), NT-proBNP (râ=â0.20, Pâ=â.02) and hsTnT (râ=â0.25, Pâ=â.004). Circulating myeloid DCPs, plasmacytoid DCPs, and total DCPs showed a significant inverse correlation to IL-16 levels (râ=â-0.21, Pâ=â.01; râ=â-0.23, Pâ=â.005; râ=â-0.26, Pâ=â.002, respectively).Interleukin-16 might play an important role in the inflammatory process of patients suffering from AMI and correlates with inflammatory cell activation and clinical and biochemical markers. The cytokine IL-16 might upregulate the proinflammatory response and recruitment of inflammatory cells into infarcted myocardium.
Assuntos
Interleucina-16/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Fragmentos de Peptídeos/sangue , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapiaRESUMO
Gastric cancer (GC) is one of the major leading causes of cancerassociated mortality worldwide. Serum biomarkers have a vital role in diagnosis and prognosis of GC, and interleukin (IL)16 may serve as a useful biomarker with prognostic value for human cancers. The current study aimed to evaluate the expression level of serum IL16 in patients with GC, and evaluate the diagnostic and prognostic value of IL16. ELISA was performed determine the serum IL16 levels in patients with GC and healthy controls. Receiver operator curve analysis was performed to evaluate the diagnostic and prognostic potential value of serum IL16 in GC diagnosis. Migration and invasion assays were performed using cells with IL16 small interfering RNA (siRNA) knockdown. The results demonstrated that serum IL16 levels were significantly higher in GC samples than in healthy controls, and increased serum IL16 levels were significantly associated with tumor recurrence and poor prognosis. Knockdown of IL16 significantly suppressed the migration and invasion of GC cells. In conclusion, the current results indicate that serum IL16 levels may have diagnostic and prognostic value for patient with GC.
Assuntos
Biomarcadores Tumorais , Interleucina-16/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Feminino , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Interleucina-16/genética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Prognóstico , Interferência de RNA , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Recidiva , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidadeRESUMO
Preeclampsia (PE), an important cause of maternal and perinatal morbidity and mortality worldwide, is a pregnancy-related disease characterized by hypertension and proteinuria after 20 weeks of gestation. The aim of our study was to find a practical panel of biomarkers useful in early diagnosis of PE. This study was carried out at the Obstetrics and Gynecology Department in Tîrgu MureÈ University Hospital, Romania, between January 2014 and July 2015 and included 68 pregnant women (47 preeclamptic women and 21 controls) with gestational age between 16 and 20 weeks at enrollment. The biomarkers PlGF, sFlt-1, sEng, IL-6, and IL-16 were determined by ELISA test. We compared the serum levels of soluble markers analysed in preeclamptic women and controls during the second and third trimesters of pregnancy and we found that the best predictor for PE was PlGF with a sensitivity of 100% at a concentration threshold of 120.16 pg/mL, a diagnosis accuracy of 70.8%, and AUC of 0.684 (p = 0.005). We also estimated the risk for PE according to BMI and we found that pregnant women with weight >90 kg had 7 times higher risk for PE. Second-trimester PlGF serum level may serve as an early biomarker for the diagnosis of PE.
Assuntos
Biomarcadores/sangue , Endoglina/sangue , Interleucina-16/sangue , Interleucina-6/sangue , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Índice de Massa Corporal , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Gravidez , Adulto JovemRESUMO
BACKGROUND: Long-term exposure to tobacco smoke causes local inflammation in the airways that involves not only innate immune cells, including NK cells, but also adaptive immune cells such as cytotoxic (CD8+) and helper (CD4+) T-cells. We have previously demonstrated that long-term tobacco smoking increases extracellular concentration of the CD4+-recruiting cytokine interleukin (IL)-16 locally in the airways. Here, we hypothesized that tobacco smoking alters IL-16 biology at the systemic level and that this effect involves oxygen free radicals (OFR). METHODS: We quantified extracellular IL-16 protein (ELISA) and intracellular IL-16 in NK cells, T-cells, B-cells, and monocytes (flow cytometry) in blood samples from long-term tobacco smokers with and without chronic obstructive pulmonary disease (COPD) and in never-smokers. NK cells from healthy blood donors were stimulated with water-soluble tobacco smoke components (cigarette smoke extract) with or without an OFR scavenger (glutathione) in vitro and followed by quantification of IL-16 protein. RESULTS: The extracellular concentrations of IL-16 protein in blood did not display any substantial differences between groups. Notably, intracellular IL-16 protein was detected in all types of blood leukocytes. All long-term smokers displayed a decrease in this IL-16 among NK cells, irrespective of COPD status. Further, both NK and CD4+ T-cell concentrations displayed a negative correlation with pack-years. Moreover, cigarette smoke extract caused release of IL-16 protein from NK cells in vitro, and this was not affected by glutathione, in contrast to the decrease in intracellular IL-16, which was prevented by this drug. CONCLUSION: Long-term exposure to tobacco smoke does not markedly alter extracellular concentrations of IL-16 protein in blood. However, it does decrease the intracellular IL-16 concentrations in blood NK cells, the latter effect involving OFR. Thus, long-term tobacco smoking exerts an impact at the systemic level that involves NK cells; innate immune cells that are critical for host defense against viruses and tumors - conditions that are overrepresented among smokers.
Assuntos
Mediadores da Inflamação/sangue , Interleucina-16/sangue , Células Matadoras Naturais/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumar/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Antioxidantes/farmacologia , Linfócitos B/imunologia , Estudos de Casos e Controles , Separação Celular/métodos , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Glutationa/farmacologia , Humanos , Interferon gama/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Estresse Oxidativo/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/etiologia , Espécies Reativas de Oxigênio/metabolismo , Fumaça/efeitos adversos , Fumar/efeitos adversos , Fumar/sangue , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/metabolismo , Fatores de TempoRESUMO
Interleukin (IL) 16 plays a key role in inflammatory diseases as well as in tumorigenesis of osteosarcoma (OS). The aim of this study was to investigate the association of IL16 polymorphisms and plasma IL16 level with OS risk in a Chinese population. We genotyped IL16 rs4778889, rs11556218, and rs4072111 in 358 patients with OS and 402 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. Plasma IL16 level was measured by enzyme-linked immunosorbent assay. Rs11556218 was associated with an increased risk of OS in heterozygote comparison (adjusted OR = 1.65, 95% CI, 1.23-2.21, P < 0.001), dominant model (adjusted OR = 1.66, 95% CI, 1.24-2.21, P < 0.001), and allele comparison (adjusted OR = 1.44, 95% CI, 1.14-1.81, P = 0.002). Moreover, rs11556218 TG/GG genotypes were associated with higher levels of IL16 as compared to TT genotype (P = 0.03). However, no significant association of rs4778889 and rs4072111 and OS was found. These findings suggest that rs11556218 TG/GG genotypes may be associated with increased susceptibility to OS, probably by increasing the production of IL16 level.
Assuntos
Alelos , Neoplasias Ósseas , Predisposição Genética para Doença , Interleucina-16 , Proteínas de Neoplasias , Osteossarcoma , Polimorfismo Genético , Adolescente , Adulto , Neoplasias Ósseas/sangue , Neoplasias Ósseas/genética , Criança , Feminino , Humanos , Interleucina-16/sangue , Interleucina-16/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Osteossarcoma/sangue , Osteossarcoma/genética , Fatores de RiscoRESUMO
The effect of hydroxychloroquine (HCQ) on dry eye has not been fully determined. This study aimed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren's syndrome (pSS). A double-blind, randomized control study was conducted in 39 pSS subjects from May 2011 through August 2013. pSS was diagnosed based on the classification criteria of the American-European Consensus Group. Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline, 6, and 12 weeks, with a re-visit at 16 weeks after drug discontinuance. The fluorescein staining score, Schirmer test score, tear film break-up time (TBUT), and ocular surface disease index (OSDI) were measured, and tears and blood were collected for ESR, IL-6, IL-17, B-cell activating factor (BAFF), and Th17 cell analysis. Color testing was performed and the fundus was examined to monitor HCQ complications. Twenty-six subjects completed the follow-up. The fluorescein staining score and Schirmer test score did not differ significantly. The OSDI improved with medication in the HCQ group but was not significantly different between the groups. TBUT, serum IL-6, ESR, serum and tear BAFF, and the proportion of Th17 cells did not change in either group. HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS (ClinicalTrials.gov. NCT01601028).
Assuntos
Síndromes do Olho Seco/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Síndrome de Sjogren/complicações , Idoso , Fator Ativador de Células B/análise , Fator Ativador de Células B/sangue , Sedimentação Sanguínea , Método Duplo-Cego , Esquema de Medicação , Síndromes do Olho Seco/complicações , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-16/análise , Interleucina-16/sangue , Interleucina-17/análise , Interleucina-17/sangue , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Estudos Prospectivos , Síndrome de Sjogren/diagnóstico , Células Th17/citologia , Células Th17/imunologia , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Increased interleukin 16 (IL-16) levels in carotid plaques have been associated with reduced incidence of cardiovascular (CV) events during follow-up in patients who underwent carotid endarterectomy (CEA). In the present study we aimed to determine whether high circulating levels of IL-16 also are associated with a decreased risk of CV events after CEA. METHODS: Patients, who had their carotid plaques surgically removed (n=473), were followed for a mean follow-up time of 3.1years. Plasma levels of IL-16 the day before surgery were analyzed by proximity extension assay (PEA) and associated with the occurrence of CV events during follow-up (n=98). RESULTS: High levels of circulating IL-16 were independently associated with a decreased risk of CV events when comparing the highest versus the lowest IL-16 tertile (hazard ratio [HR] 0.47; 95% CI 0.27-0.81; P=0.007), as well as with CV deaths (HR 0.25; 95% CI 0.09-0.70; P=0.008). CONCLUSION: These present findings indicate an association between IL-16 and less clinical complications of atherosclerosis in a population with known advanced carotid disease.
Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Interleucina-16/sangue , Idoso , Endarterectomia das Carótidas/métodos , Feminino , Seguimentos , Humanos , Masculino , Fatores de RiscoRESUMO
CONCLUSIONS: Vestibular function disorders were widespread among nasopharyngeal carcinoma (NPC) patients. The radiation doses to the inner ears were associated with the incidence of vestibular function disorders, but the correlations were mild. The inflammatory responses and possible resolution obstacles of inflammation participated in persistent vestibular function disorders after irradiation. OBJECTIVES: To investigate the incidence of vestibular function disorders in NPC patients after irradiation and potential mechanisms. METHODS: Patients who received radical intensity-modulated radiotherapy for their NPC were recruited. The serum levels of IL-6 and IL-17 were detected by ELISA method. Vestibular evoked myogenic potential (VEMP) tests were used to evaluate vestibular function and correlation analyses were used to analyze the potential mechanisms of vestibular function disorders. RESULTS: Thirty-eight patients were included. The incidences of abnormal ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were 65.79% and 80.26% at the time of completion of radiotherapy, and 61.84% and 71.05% at 3 months after radiotherapy. The mean and maximum radiation doses to the inner ears were both significantly associated with abnormal oVEMP and cVEMP (p < 0.05, all), but the correlations were all mild. The serum levels of IL-6 and IL-17 were both significantly associated with abnormal oVEMP and cVEMP after irradiation (p < 0.05, all).
Assuntos
Carcinoma/radioterapia , Orelha Interna/efeitos da radiação , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Doenças Vestibulares/etiologia , Adulto , Idoso , Carcinoma/complicações , Feminino , Humanos , Interleucina-16/sangue , Interleucina-17/sangue , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/complicações , Otite Média/complicações , Doses de Radiação , Doenças Vestibulares/sangueRESUMO
Recently, differences in the levels of various chemokines and cytokines were reported in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared with controls. Moreover, the analyte profile differed between chronic ME/CFS patients of long duration versus patients with disease of less than 3years. In the current study, we measured the plasma levels of 34 cytokines, chemokines and growth factors in 100 chronic ME/CFS patients of long duration and in 79 gender and age-matched controls. We observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and Vascular Endothelial Growth Factor A (VEGF-A) in ME/CFS patients. All three biomarkers were significantly correlated in a multivariate cluster analysis. In addition, we identified significant reductions in the concentrations of fractalkine (CX3CL1) and monokine-induced-by-IFN-γ (MIG; CXCL9) along with increases in the concentrations of eotaxin 2 (CCL24) in ME/CFS patients. Our data recapitulates previous data from another USA ME/CFS cohort in which circulating levels of IL-7 were reduced. Also, a reduced level of VEGF-A was reported previously in sera of patients with Gulf War Illness as well as in cerebral spinal fluid samples from a different cohort of USA ME/CFS patients. To our knowledge, we are the first to test for levels of IL-16 in ME/CFS patients. In combination with previous data, our work suggests that the clustered reduction of IL-7, IL-16 and VEGF-A may have physiological relevance to ME/CFS disease. This profile is ME/CFS-specific since measurement of the same analytes present in chronic infectious and autoimmune liver diseases, where persistent fatigue is also a major symptom, failed to demonstrate the same changes. Further studies of other ME/CFS and overlapping disease cohorts are warranted in future.
Assuntos
Síndrome de Fadiga Crônica/sangue , Interleucina-16/sangue , Interleucina-7/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocinas/sangue , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Análise MultivariadaRESUMO
Whipple's disease (WD) is a rare systemic condition caused, in genetically predisposed subjects, by Tropheryma whipplei, a common bacterium widespread in the environment. The relevance of genetic predisposition in WD is shown by the association with HLA alleles DRB1*13 and DQB1*06 and by the demonstration that, in patients with WD, the cytokine genetic profile is skewed toward a Th2 and Treg response. Since IL-16 is involved in hampering the development of a protective macrophagic response against Tropheryma whipplei, we investigated whether the genetic background of IL-16 is different between patients with WD and controls. The -295 T-to-C polymorphism of the promoter region of the IL-16 gene was studied in 90 patients with WD and 152 healthy controls. Levels of serum IL-16 protein were also tested. The frequency of the wild type T allele was significantly higher in patients with WD compared to the controls (155/180 vs. 235/304; p = 0.02 for the Chi(2) test), odds ratio 1.82 [95 % confidence interval (CI) 1.07-3.10]. The TT genotype was found in 65/90 patients with WD and 88/152 controls (p = 0.026). No relationship was found between serum levels of IL-16 and genotypes. Although the functional consequences of this genetic background on levels of IL-16 and on the course of the disease are still unknown, we found, for the first time, that the wild type T allele and the TT genotype of the -295 polymorphism are associated with WD.
Assuntos
Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Interleucina-16/genética , Regiões Promotoras Genéticas/genética , Doença de Whipple/genética , Adulto , Alelos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Interleucina-16/sangue , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Tropheryma/imunologia , Doença de Whipple/imunologia , Doença de Whipple/microbiologiaRESUMO
BACKGROUND: Interleukin-16 (IL-16), a pleiotropic cytokine, plays a fundamental role in inflammatory diseases. This study investigates the association between IL-16 polymorphisms and the risk of knee osteoarthritis (OA) in a Chinese population. METHODS: The IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms were determined in 150 knee OA cases and 147 healthy controls through polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The results suggested that the variants in IL-16 gene rs11556218 site were associated with a decreased knee OA risk after adjusting for age, sex, BMI, and smoking and drinking status (TG vs. TT: OR, 0.69; 95% CI, 0.53-0.89; P = 0.006; GG vs. TT: OR, 0.64; 95% CI, 0.45-0.90; P = 0.042; dominant model: OR, 0.68; 95% CI, 0.29-0.87; P = 0.002; G vs. T allele: OR, 0.77; 95% CI, 0.66-0.90; P = 0.003). Similarly, subjects bearing the rs4072111 variant genotypes and alleles also had a lower susceptibility to knee OA compared with those bearing the wild-type (CT vs. CC: OR, 0.66; 95% CI, 0.53-0.83; P = 0.002; TT vs. CC: OR, 0.57; 95% CI, 0.40-0.82; P = 0.027; dominant model: OR, 0.65; 95%, CI 0.52-0.80; P <0.001; T vs. C allele: OR, 0.69; 95% CI, 0.58-0.81; P <0.001). Further, the C allele and the combined genotype (CC+CT) of rs4778889 were associated with a slightly decreased risk of knee OA. In addition, we found two high-risk haplotypes: TTT (OR, 3.70) and GCC (OR, 6.22). Finally, serum IL-16 levels of knee OA patients were significantly higher than those of controls (P = 0.001). CONCLUSIONS: Despite the small sample size, this is the first study suggesting IL-16 gene polymorphisms to be associated with the risk of knee OA.