RESUMEN
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).
Asunto(s)
Síndromes de Ojo Seco/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Síndrome de Sjögren/complicaciones , Anciano , Factor Activador de Células B/análisis , Factor Activador de Células B/sangre , Sedimentación Sanguínea , Método Doble Ciego , Esquema de Medicación , Síndromes de Ojo Seco/complicaciones , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-16/análisis , Interleucina-16/sangre , Interleucina-17/análisis , Interleucina-17/sangre , Masculino , Persona de Mediana Edad , Efecto Placebo , Estudios Prospectivos , Síndrome de Sjögren/diagnóstico , Células Th17/citología , Células Th17/inmunología , Resultado del TratamientoRESUMEN
RATIONALE: Neuroendocrine-immune regulation is essential for maintaining health. Early-life adversity may cause dysregulation in the neuroendocrine-immune network through repeated activation of the stress response, thereby increasing disease risk. OBJECTIVE: This paper examined the extent to which maternal psychological well-being moderates neuroendocrine-immune relations in children. METHODS: We used data from a laboratory-based study of mothers and their five-year old children (n = 125 mother-child pairs) conducted from 2011 to 2013 in Baltimore, Maryland. Child saliva was assayed for markers of immune function (i.e., cytokines: interleukin [IL]-1ß, IL-6, IL-8, tumor necrosis factor alpha [TNF-α]) and hypothalamic-pituitary-adrenal activity (i.e., cortisol). A composite score for depressive symptoms, anxiety, and parenting stress characterized maternal psychological distress. Multilevel mixed models examined the relationship between maternal psychological well-being and child neuroendocrine-immune relations. RESULTS: Significant cytokine × maternal distress interactions indicated that as maternal distress increased, expected inverse cytokine-cortisol relations within children became weaker for IL-1ß, IL-6, and TNF-α. Sex-stratified models revealed that these interactions were only significant among girls. Among boys, there were inverse cytokine-cortisol relations for all cytokines, and, while in the same direction as observed among girls, the cytokine × maternal distress interactions were non-significant. CONCLUSION: The findings suggest that maternal distress is associated with child neuroendocrine-immune relations in saliva and may alter the sensitivity of inflammatory immune processes to cortisol's inhibitory effects. This desensitization may place the child at risk for inflammatory diseases. The findings support efforts for the early detection and treatment of at-risk mothers to protect maternal and child health and well-being.
Asunto(s)
Salud Infantil/normas , Salud Materna/normas , Relaciones Madre-Hijo/psicología , Sistemas Neurosecretores/metabolismo , Estrés Psicológico/complicaciones , Trastornos de Ansiedad/complicaciones , Baltimore , Preescolar , Depresión/complicaciones , Femenino , Humanos , Interleucina-16/análisis , Interleucina-1beta/análisis , Masculino , Sistemas Neurosecretores/inmunología , Receptores del Factor de Necrosis Tumoral/análisis , Saliva/metabolismoRESUMEN
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).
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factor Activador de Células B/análisis , Sedimentación Sanguínea , Método Doble Ciego , Esquema de Medicación , Síndromes de Ojo Seco/complicaciones , Ensayo de Inmunoadsorción Enzimática , Hidroxicloroquina/uso terapéutico , Interleucina-16/análisis , Interleucina-17/análisis , Efecto Placebo , Estudios Prospectivos , Síndrome de Sjögren/complicaciones , Células Th17/citología , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Interleukin-16 (IL-16) functions as a regulator of T-cell growth and acts as an inducer of cell migration. The aim of this study was to determine whether IL-16 measured in human carotid plaques was associated with symptoms (eg, stroke, transient ischemic attack, or amaurosis fugax), markers of plaque stability, and postoperative cardiovascular events. METHODS: Plaques obtained from patients who had ≥1 cerebrovascular ischemic events within 1 month before endarterectomy (n=111) were compared with plaques from patients without symptoms (n=95). Neutral lipids, smooth muscle cell, and macrophage contents were evaluated histologically, and collagen, elastin, and caspase-3 activity were measured biochemically. IL-16, matrix metalloproteinases, and tissue inhibitors of metalloproteinases were measured in plaque homogenates using a multiplex immunoassay. IL-16, CD3, CD4, and FoxP3 mRNA expressions in carotid plaques were analyzed with quantitative real-time polymerase chain reaction. RESULTS: Carotid plaques from asymptomatic patients had higher levels of IL-16 mRNA. High plaque IL-16 protein levels (above median) were associated with reduced incidence of postoperative cardiovascular events during a mean follow-up of 21 months (hazard ratio, 0.47; 95% confidence interval, 0.22-0.99; P=0.047). IL-16 levels correlated with the plaque-stabilizing components: elastin, collagen, matrix metalloproteinase-2, tissue inhibitors of metalloproteinase-1, tissue inhibitors of metalloproteinase-2 and FoxP3 mRNA. CONCLUSIONS: This study shows that high levels of IL-16 are associated with asymptomatic carotid plaques, expression of factors contributing to plaque stability, and decreased risk of new cardiovascular events during a 2-year period after surgery, suggesting that IL-16 might have a protective role in human atherosclerotic disease.
Asunto(s)
Estenosis Carotídea/complicaciones , Estenosis Carotídea/inmunología , Interleucina-16/biosíntesis , Arteriosclerosis Intracraneal/epidemiología , Ataque Isquémico Transitorio/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Biomarcadores/análisis , Femenino , Humanos , Interleucina-16/análisis , Arteriosclerosis Intracraneal/etiología , Ataque Isquémico Transitorio/etiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Accidente Cerebrovascular/etiologíaRESUMEN
Objetivo Comparar las concentraciones de interleucina-16 en pacientes con preeclampsia y gestantes normotensas sanas. Método Se seleccionó un total de 100 pacientes. Se incluyeron 50 pacientes con preeclampsia como grupo de estudio (grupo A) y un grupo de control seleccionado por tener una edad y un índice de masa corporal similares al grupo de estudio que consistió en 50 gestantes normotensas sanas (grupo B). Las muestras de sangre se recolectaron en todas las pacientes antes del parto e inmediatamente después del diagnóstico en el grupo B para determinar las concentraciones de interleucina-16.ResultadosSe encontraron diferencias estadísticamente significativas en las concentraciones de interleucina-16 entre las pacientes del grupo de estudio (grupo A: 211,9 ± 78,7 pg/ml) y las pacientes del grupo de control (grupo B: 83,6 ± 9,9 pg/ml; p < 0,05). Se observó una correlación fuerte, positiva y significativa con los valores de presión arterial sistólica (r = 0,282; p < 0,05) y con los valores de presión arterial diastólica (r = 0,320; p < 0,05). Un valor de corte de 180 pg/ml presentó un valor por debajo de la curva de 0,95, una sensibilidad del 94,0%, especificidad del 70,0%, valor predictivo positivo del 75,8% y valor predictivo negativo del 92,1%, con una exactitud diagnóstica del 75,0%.ConclusionesLas pacientes con preeclampsia presentaron concentraciones significativamente más altas de interleucina-16 al compararlo con gestantes normotensas sanas (AU)
Objective To compare interleukin-16 concentrations in patients with preeclampsia and healthy normotensive pregnant women. Method A total of 100 patients were selected. Fifty patients with preeclampsia were selected as the study group (group A) and 50 healthy normotensive pregnant women with the same age and body mass index as the study group were selected as controls (group B). Blood samples were extracted from all patients before labor and immediately after diagnosis in group B to determine interleukin-16 concentrations. Results There was statistically significant difference in interleukin-16 concentrations between group A (211.9 ± 78.7 pg/ml) and group B (83.6 ± 9.9 pg/ml; p < 0.05). There was a strong, positive and significant correlation with systolic blood pressure values (r = 0.282; p < 0.05) and with diastolic blood pressure values (r = 0.320; p < 0.05). A cutoff value of 180 pg/ml had an area under the curve of 0.95, sensitivity of 94.0%, specificity of 70.0%, a positive predictive value of 75.8% and a negative predictive value of 92.1%, with a diagnostic accuracy of 75.0%.ConclusionsInterleukin-16 concentrations were significantly higher in patients with preeclampsia than in healthy normotensive pregnant women (AU)
Asunto(s)
Humanos , Femenino , Embarazo , Interleucina-16/análisis , Preeclampsia/fisiopatología , Complicaciones del Embarazo/diagnóstico , Biomarcadores/análisisRESUMEN
OBJECTIVE: Infection is believed to be one of frequent and important causes of preterm labor. We attempted to evaluate whether the level of inflammatory markers, e.g. interleukin-16 (IL-16), interleukin-18 (IL-18), and ferritin, in amniotic fluid at early second trimester can predict preterm birth. METHODS: Amniotic fluid (AF) samples were collected from 350 pregnant women who had trans-abdominal amniocentesis for genetic indications at 16 to 20 weeks of gestation. AF levels of IL-16, IL-18 and ferritin levels were measured by immunoassay and were correlated with pregnancy outcomes. RESULTS: Among the 350 pregnant women, 58 (16.6%) had preterm birth (<37 weeks gestation). AF levels of IL-16, IL-18, and ferritin were significantly higher in pregnant women with subsequent preterm birth. Multivariate analyses showed that a quartile higher of AF IL-16 level was significantly associated with preterm birth (OR: 3.09, 95% CI 1.52-6.27, p = 0.002). A receiver operating characteristic analysis revealed that an IL-16 cutoff value of 105 pg/ml was a reliable predictor of preterm birth (sensitivity, 90.2%; specificity, 52.7%; negative predictive value, 84.3%). CONCLUSION: It is feasible to predict preterm birth by measuring the AF levels of IL-16 especially for the pregnant women requiring genetic amniocentesis during early second trimester.
Asunto(s)
Líquido Amniótico/química , Interleucina-16/análisis , Interleucina-16/metabolismo , Segundo Trimestre del Embarazo/metabolismo , Nacimiento Prematuro/diagnóstico , Adulto , Amniocentesis , Biomarcadores/análisis , Estudios de Factibilidad , Femenino , Edad Gestacional , Humanos , Recién Nacido , Concentración Osmolar , Embarazo , PronósticoRESUMEN
Omalizumab is an anti-IgE monoclonal antibody that was proven effective for the treatment of severe asthma. IgE plays a central role in allergic asthma, and an anti-allergic effect of omalizumab has been confirmed in terms of its impact on Th2 cytokines. The objective of the present study is to determine the influence of omalizumab on clinical parameters and circulating immuoregulatory cytokines. Patients with severe allergic asthma were enrolled and given four months of omalizumab therapy. Changes of symptoms and other parameters were assessed, including the asthma control test (ACT) score, morning peak expiratory flow (PEF), peripheral eosinophil count, total serum IgE, and pulmonary function tests. The use of corticosteroids and short-acting bronchodilators, as well as the number of unscheduled hospital visits, were monitored. Circulating levels of cytokines were analyzed with a multiplex cytokine immunoassay in patients with or without omalizumab therapy. Asthma symptoms (evaluated by the ACT score and morning PEF) improved with omalizumab treatment, while total IgE was elevated. Use of corticosteroids and short-acting bronchodilators and the number of unscheduled hospital visits for exacerbation of asthma were all reduced by omalizumab treatment. The level of macrophage inflammatory protein 1-δ (MIP1-δ) was significantly reduced after omalizumab therapy and was high in patients without omalizumab. IL-16 also tended to decrease with omalizumab therapy. Both MIP1-δ and IL-16 decreased as asthma improved over the 4-month period of omalizumab therapy. These findings suggest that omalizumab may act via IgE-mediated immunoregulation of MIP1-δ and IL-16.
Asunto(s)
Antiasmáticos/administración & dosificación , Anticuerpos Antiidiotipos/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Asma , Inmunoglobulina E/inmunología , Factores Inmunológicos/administración & dosificación , Interleucina-16/análisis , Proteínas Inflamatorias de Macrófagos/análisis , Macrófagos/efectos de los fármacos , Corticoesteroides/farmacología , Adulto , Anciano , Antiasmáticos/uso terapéutico , Anticuerpos Antiidiotipos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Asma/tratamiento farmacológico , Asma/inmunología , Asma/fisiopatología , Regulación hacia Abajo , Femenino , Humanos , Inmunoglobulina E/biosíntesis , Factores Inmunológicos/uso terapéutico , Interleucina-16/biosíntesis , Pulmón/fisiopatología , Proteínas Inflamatorias de Macrófagos/biosíntesis , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Omalizumab , Proyectos de Investigación , Pruebas de Función Respiratoria , Resultado del TratamientoAsunto(s)
Interleucina-11/fisiología , Interleucina-12/fisiología , Interleucina-13/fisiología , Interleucina-15/fisiología , Interleucina-16/fisiología , Interleucina-17/fisiología , Interleucina-18/fisiología , Interleucinas/fisiología , Biomarcadores/análisis , Ensayo de Inmunoadsorción Enzimática/métodos , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/terapia , Humanos , Enfermedades del Sistema Inmune/diagnóstico , Enfermedades del Sistema Inmune/terapia , Inflamación/diagnóstico , Inflamación/terapia , Interleucina-11/análisis , Interleucina-11/uso terapéutico , Interleucina-12/análisis , Interleucina-12/uso terapéutico , Interleucina-13/análisis , Interleucina-13/uso terapéutico , Interleucina-15/análisis , Interleucina-15/uso terapéutico , Interleucina-16/análisis , Interleucina-16/uso terapéutico , Interleucina-17/análisis , Interleucina-17/uso terapéutico , Interleucina-18/análisis , Interleucina-18/uso terapéutico , Interleucinas/análisis , Interleucinas/uso terapéutico , Valores de Referencia , Manejo de EspecímenesRESUMEN
OBJECTIVE: To investigate the role of interleukine-16 (IL-16) in the pathogenesis of endometriosis. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IL-16 in peritoneal fluid and serum specimens of 22 women with different stage endometriosis and 22 controls. RESULTS: The median levels of IL-16 in peritoneal fluid and serum were 290.5 pg/ml and 539.4 pg/ml in women with endometriosis, and 296.6 pg/ml and 778.1 pg/ml in controls, respectively; there was no significant difference between two groups (P>0.05). However, the IL-16 levels in peritoneal fluid and serum of patients with minimal/mild stage endometriosis and controls were all significantly higher than those of patients with moderate/severe endometriosis (P<0.01, <0.05). In addition, there was no statistical correlation of peritoneal IL-16 levels with those in serum (P>0.05). CONCLUSION: Reduced levels of IL-16 in peritoneal fluid and serum of women with advanced stage endometriosis may imply a role of IL-16 in the development and progression of endometriosis.
Asunto(s)
Líquido Ascítico/química , Endometriosis/metabolismo , Interleucina-16/análisis , Adulto , Femenino , Humanos , Interleucina-16/sangre , Persona de Mediana EdadRESUMEN
The aim of this study was to explore the presence of interleukin (IL)-16 in pleural effusions, the correlation between IL-16 levels and cytological parameters, as well as the chemoattractant activity of IL-16 on CD4+ T-lymphocytes. Total nucleated cell and differential counts, and IL-16 concentrations in the pleural effusion from 32 patients with tuberculous pleurisy and 30 patients with lung cancer were determined. Three-colour flow cytometry was performed to determine T-lymphocyte subsets in cell pellets of pleural effusion. The chemoattractant activity of IL-16 for CD4+ T-lymphocytes was also analysed. The levels of IL-16 were significantly higher in tuberculous than in malignant effusions. However, IL-16 levels could not be used for diagnostic purposes due to significant overlap between the two groups. Positive correlations were found between the IL-16 levels and CD4+ T-cells, and pleural fluid was chemotactic for CD4+ T-cells in vitro. Intrapleural administration of IL-16 to patients produced a marked progressive influx of CD4+ T-cells into the pleural space. Compared with malignant pleural effusion, interleukin-16 appeared to be increased in tuberculous pleural effusion. Interleukin-16 levels were positively related to the numbers of CD4+ T-cells, and interleukin-16 could directly induce CD4+ T-cell infiltration into the pleural space.
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Interleucina-16/análisis , Neoplasias Pulmonares/inmunología , Derrame Pleural/química , Tuberculosis Pulmonar/inmunología , Adulto , Anciano , Linfocitos T CD4-Positivos/fisiología , Quimiotaxis de Leucocito , Humanos , Persona de Mediana Edad , Derrame Pleural Maligno/químicaAsunto(s)
Líquido Ascítico/inmunología , Endometriosis/inmunología , Interleucina-16/análisis , Adulto , Líquido Ascítico/química , Estudios de Casos y Controles , Endometriosis/sangre , Endometriosis/cirugía , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-16/sangre , Activación de Linfocitos , Estadísticas no ParamétricasRESUMEN
CD4(+) and CD8(+) lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8(+) cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4(+) lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4(+) or CD8(+) lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2Ralpha) protein were also measured in conditioned medium from human blood CD4(+) and CD8(+) lymphocytes stimulated with tobacco smoke extract (TSE) in vitro. IL-16 mRNA was assessed in vitro as well, using reverse transcription-polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2Ralpha in conditioned medium from CD4(+) and CD8(+) lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8(+) cytokine IL-16, in the airway lumen, in blood CD4(+) and CD8(+) lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4(+) lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD.
Asunto(s)
Líquido del Lavado Bronquioalveolar/química , Interleucina-16/análisis , Tejido Linfoide/química , Nicotiana/efectos adversos , Humo/efectos adversos , Linfocitos T/química , Adulto , Anciano , Bronquitis/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Linfocitos T CD4-Positivos/química , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/química , Linfocitos T CD8-positivos/inmunología , Enfermedad Crónica , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Inmunohistoquímica/métodos , Subunidad alfa del Receptor de Interleucina-2 , Tejido Linfoide/inmunología , Masculino , Persona de Mediana Edad , Tonsila Palatina/química , Tonsila Palatina/inmunología , ARN Mensajero/análisis , Receptores de Interleucina/análisis , Linfocitos T/inmunología , Nicotiana/inmunologíaRESUMEN
BACKGROUND: In rheumatoid arthritis (RA), synovial fibroblast-like cells (SF) contribute significantly to articular inflammation. They express distinct patterns of genes associated with cell proliferation and differentiation and elevated levels of cytokines and chemoattractant factors, including IL-16. Here we investigated pathways regulating IL-16 expression in fibroblasts from RA patients in comparison to fibroblasts from osteoarthritis (OA) patients. METHODS: Fibroblasts were isolated from dermal and articular biopsies, expanded and pathways of IL-16 induction were investigated by real time quantitative RT/PCR, immuno blot and ELISA. RESULTS: Stimulation of cAMP dependent signal transduction by forskolin induced prominent IL-16 RT/PCR signals in OA-DF and OA-SF. In contrast, in RA-DF and RA-SF staurosporine significantly augmented IL-16 RT/PCR signals, but forskolin induced less IL-16 transcript amounts. Activation of protein kinase C by PMA induced a significant IL-16 response only in RA-SF. Addition of IL-1beta or TNF-alpha did not upregulate IL-16 mRNA but secretion of the mature IL-16 cytokine was activated in serum starved cells in presence of IL-1beta. CONCLUSION: Our results suggest that RA fibroblasts differ from OA fibroblasts with respect to their sensitivities to kinase/phospatase signal transduction pathways. The enhanced expression of IL-16 in the synovial membrane early in RA vs OA may be associated in part with these distinct signaling responses.
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Artritis Reumatoide/metabolismo , Fibroblastos/metabolismo , Regulación de la Expresión Génica , Interleucina-16/genética , Osteoartritis/metabolismo , Transducción de Señal , Membrana Sinovial/citología , Artritis Reumatoide/genética , Extractos Celulares/química , Células Cultivadas , Colforsina/farmacología , AMP Cíclico/fisiología , Fibroblastos/efectos de los fármacos , Humanos , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-16/análisis , Interleucina-16/metabolismo , Osteoartritis/genética , Proteínas Serina-Treonina Quinasas/fisiología , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Transducción de Señal/fisiología , Estaurosporina/farmacologíaRESUMEN
Cutaneous infiltration of activated CD4(+) T cells and eosinophils is an early event in blister formation during bullous pemphigoid (BP), suggesting that the trafficking of circulating leucocytes through the sites of inflammation, their activation and cytokine release is crucial in the pathogenesis of the disease. IL-16 is a major chemotactic factor able to recruit CD4(+) cells in the skin during inflammation and to induce the expression of functional high-affinity interleukin (IL)-2 receptors, thus contributing to cellular activation and proliferation. We performed a study in order to evaluate the presence of IL-16 in skin samples and sera and blister fluids of patients affected with BP in active phase of the disease (n = 39), compared with healthy donors studied as control group. Ten patients were also evaluated before and after steroid therapy. Our results demonstrated that IL-16 was expressed strongly by keratinocytes and by dermal infiltrating CD4(+) T lymphocytes in lesional skin of BP patients. High levels of IL-16 were detected in sera and blisters of BP, significantly higher in respect to healthy donors. When patients were investigated for the presence of eosinophil cationic protein (ECP) and soluble CD30 (sCD30) to reveal signs of eosinophils and Th2-cells activation, we found a positive correlation between IL-16 serum levels and both ECP and sCD30, suggesting that IL-16 is involved in Th2 lymphocytes and eosinophils recruitment during BP.
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Interleucina-16/análisis , Penfigoide Ampolloso/inmunología , Piel/inmunología , Enfermedad Aguda , Anciano , Proteínas Sanguíneas/análisis , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Proteínas en los Gránulos del Eosinófilo , Eosinófilos/inmunología , Femenino , Humanos , Recuento de Leucocitos , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Ribonucleasas/análisis , Células Th2/inmunologíaRESUMEN
Constitutive expression of the pro-molecule of IL-16 has been found in T cells, mast cells, eosinophils, epithelial cells, fibroblasts, and dendritic cells. Here we show that IL-16 is also constitutively present in >98% of freshly isolated human CD14-positive peripheral blood monocytes when analyzed by flow cytometry. Because pro-IL-16 is cleaved to its bioactive mature form by caspase-3, and caspase-3 is also the pivotal effector of apoptosis in monocytes, we asked whether IL-16 release occurs in monocytes that undergo spontaneous apoptosis. As expected, freshly isolated, unstimulated monocytes underwent spontaneous caspase-3 activation. This apoptosis was paralleled by the loss of intracellular IL-16, as detected by flow cytometry, and the concurrent release of IL-16, as detected by ELISA. In contrast, stimulation with bacterial LPS inhibited caspase-3 activation and significantly inhibited the release of IL-16. As a specificity control, IL-1beta and IL-8 were not released during spontaneous monocyte apoptosis. In summary, our data demonstrate that monocytes contain IL-16 that is released during spontaneous apoptosis.
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Apoptosis , Interleucina-16/metabolismo , Monocitos/metabolismo , Células Sanguíneas , Caspasa 3 , Caspasas/metabolismo , Células Cultivadas , Humanos , Mediadores de Inflamación/farmacología , Interleucina-16/análisis , Cinética , Receptores de Lipopolisacáridos/análisis , Lipopolisacáridos/farmacología , Monocitos/químicaRESUMEN
Asthma is a chronic inflammatory disease of bronchial mucosa, in which mast cells, eosinophils and activated T cells are of considerable importance. The increased chemotactic activity for T cells in patients with asthma is mainly attributable to IL-16. A strong association between asthma and allergic rhinitis exists from a clinical and epidemiologic standpoint of view. Although it is clear that the condition of the upper airways has impact on the lower airway physiology, the precise mechanisms underlying this relation are far from being resolved. This work was assessed the role of interleukin 16 (IL-16) in bronchoalveolar lavage (BAL) fluid in both diseases using quantitative sandwich enzyme immuno-assay, and the effect on ventilatory function. The results showed abnormally increased levels of IL-16 (294.4 +/- 15.24 pg/ml), serum eosinophils with absolute count (510.0 +/- 93.57, P>0.05), and total serum IgE (287.9 +/- 61.22 IU/ml) using ELFA in patients of combined asthma and rhinitis, than in each of them alone. There was reduction in FEV1 (forced expiratory volume in the first second) in the same group (81.6 +/- 2.01%). There was a negative correlation between BAL IL-16 and FEV1. In conclusion IL-16 may be considered as a marker of severity of airway inflammation.
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Asma/inmunología , Eosinófilos/citología , Interleucina-16/sangre , Cavidad Nasal/química , Cavidad Nasal/inmunología , Rinitis/inmunología , Adolescente , Adulto , Asma/sangre , Biomarcadores/análisis , Biomarcadores/sangre , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Eosinófilos/inmunología , Femenino , Volumen Espiratorio Forzado , Humanos , Inmunoglobulina E/sangre , Interleucina-16/análisis , Recuento de Leucocitos , Masculino , Cavidad Nasal/fisiopatología , Valor Predictivo de las Pruebas , Rinitis/sangreRESUMEN
PROBLEM: To determine if interleukin-16 (IL-16), IL-17, and IL-18 are present at the murine fetomaternal interface during pregnancy as a first step towards investigating their roles in fetomaternal relationship. METHODS: Expression of IL-16, IL-17, and IL-18, was assessed by immunohistochemistry (IHC) in the BALB/c x BALB/k (H2d x H2k), and the CBA/J x BALB/c non-abortion prone, and CBA/J x DBA/2 abortion prone matings. Enzyme-linked immunosorbent assay (ELISA) were performed for the two latter cytokines to compare local production in the abortion prone CBA/J x DBA/2 versus the non-abortion prone CBA/J x BALB/c matings. RESULTS: Expression of IL-17 was borderline. The anti-IL-16 staining specifically localized in the uterine stroma and glandular epithelium and was rather low in the placenta. IL-18 staining started in the peri-implantation uterus in the basal proliferative stroma, and was also traced, although weaker, in the glandular epithelium. In the immediate post-implantation period, a weak stromal staining persisted but there was a strong labeling of the ectoplacental cone. Interestingly, when the ectoplacental cone differentiates into placenta having a major histocompatibility complex (MHC) class I + spongiotrophoblast and a (MHC class I-) labyrinth, a very strong transient labeling of uterine natural killer (u-NK) cells was found. Later in gestation, IL-18 was also produced by giant cell and spongiotrophoblast. Finally, we compared by ELISA the production of IL-17/-18 in CBA/J x DBA/2 and CBA/J x BALB/c matings. We detected significantly more IL-18 in the non-abortion prone combination decidua or placenta. CONCLUSION: The three cytokines IL-16, IL-17, and IL-18 were detected at the fetomaternal interface with a tissue specific, stage-dependent distribution. The predominance of IL-18 secretion in the non-resorption prone matings lead us to question the general validity of the classical T-helper (Th)1/2 paradigm.
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Interleucina-16/metabolismo , Interleucina-17/metabolismo , Interleucina-18/metabolismo , Placenta/metabolismo , Animales , Decidua/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Inmunohistoquímica , Interleucina-16/análisis , Interleucina-17/análisis , Interleucina-18/análisis , Ratones , Embarazo , Factores de TiempoRESUMEN
OBJECTIVE: To determine the effect of caprine arthritis-encephalitis virus (CAEV) infection on expression of interleukin-16 (IL-16). ANIMALS: 6 goats experimentally infected with CAEV and 6 age-matched healthy uninfected control goats. PROCEDURE: Peripheral blood mononuclear cells (PBMCs) and synovial membrane cells from infected and control goats cultured with or without phytohemagglutinin were analyzed for IL-16 mRNA by use of a reverse transcriptase-polymerase chain reaction assay with goat-specific primers, after cloning and sequencing of a 384-bp fragment of the goat IL-16 gene. Synovial fluid, serum, and culture supernatants of PBMCs and synovial cells of control and CAEV-infected goats were analyzed for IL-16 by use of an ELISA. RESULTS: The 384-bp product was 86% homologous to the corresponding human IL-16 nucleotide sequence. Higher expression of IL-16 mRNA in PBMCs (unstimulated or stimulated with phytohemagglutinin) was detected in samples from CAEV-infected goats, compared with control goats, but the difference was not significant. Synovial membrane cells infected in vitro had higher expression than uninfected control cells. Higher IL-16 concentration was detected in synovial fluid, serum, and culture supernatants of PBMCs of infected goats than in samples from control goats. CONCLUSIONS AND CLINICAL RELEVANCE: infection with CAEV increases expression of IL-16, a proinflammatory and chemotactic cytokine. This cytokine appears to be constitutively expressed at low concentrations in normal uninfected PBMCs and synovial membrane cells. Increased production of IL-16 in CAEV infection may partly be responsible for increased lymphoid cell infiltrations observed in arthritic joints and other tissues of CAEV-infected goats.
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Virus de la Artritis-Encefalitis Caprina/fisiología , Regulación de la Expresión Génica , Cabras/genética , Cabras/virología , Interleucina-16/genética , Infecciones por Lentivirus/genética , Animales , Secuencia de Bases , Interleucina-16/análisis , Interleucina-16/sangre , Leucocitos Mononucleares/metabolismo , Datos de Secuencia Molecular , ARN Mensajero/genética , ARN Mensajero/metabolismo , Homología de Secuencia de Ácido Nucleico , Líquido Sinovial/metabolismo , Membrana Sinovial/citología , Membrana Sinovial/metabolismoRESUMEN
BACKGROUND: T-cell activation, the key event in the development of acute allograft rejection, depends on co-stimulatory signals delivered by antigen-presenting cells (APC). APC-derived cytokines may provide co-stimulation and modulate alloimmune reaction. We have studied cytokine synthesis by fine-needle aspiration biopsy (FNAB) culture and we found significant differences for interleukin (IL)-2, IL-6, IL-10, M-CSF and IL-1ra on comparing acute rejection versus stable kidney transplant patients. We report our findings on FNAB cultures synthesis of IL-7, IL-15, IL-16, IL-17, IL-18 and RANTES (regulated upon activation, normal T-cell expressed and secreted), all potential modulators of anti-graft reaction. PATIENTS AND METHODS: Kidney transplants (KTX) treated with CsA-AZA-Pred from the beginning, were divided into four groups. Group I: day 7 post-KTX, stable; II: day 7 post-KTX, 6.5 +/- 5.5 days before acute rejection; III: first day of acute rejection; IV: day 14 post-KTX, stable. Patients from I and IV remained rejection-free for the first 6 months, at least. All rejection episodes were confirmed by classical core renal biopsy. FNAB samples were cultured according to our published methodology and culture supernatants were collected at 48 h and analysed by ELISA for IL-7, IL-15, IL-16, IL-17, IL-18 and RANTES. RESULTS: Group III synthesized significantly higher amounts of IL-7, IL-16 and IL-18 than stable patients (groups I and IV). RANTES production did not show significant differences among the four groups. We did not find any trace of IL-15. CONCLUSIONS: IL-18 may play the activation role that has been attributed to IL-12 which previously, we did not find to correlate significantly with acute rejection in KTX. IL-16 seems to play an activation role rather than an inhibition of anti-graft reaction. We confirm that RANTES is not significantly associated with acute rejection in KTX.
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Rechazo de Injerto/patología , Interleucinas/análisis , Trasplante de Riñón , Enfermedad Aguda , Adolescente , Adulto , Biopsia con Aguja , Quimiocina CCL5/análisis , Femenino , Rechazo de Injerto/inmunología , Humanos , Interleucina-16/análisis , Interleucina-18/análisis , Interleucina-7/análisis , Riñón/inmunología , Riñón/patología , Riñón/cirugía , Masculino , Persona de Mediana Edad , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: The factors controlling infiltration of inflammatory cells into atopic dermatitis (AD) lesions remain to be fully explored. Recently, epidermal cells in lesional AD were reported to contain increased messenger (m)RNA levels of IL-16, a cytokine that induces chemotactic responses in CD4(+)T cells, monocytes, and eosinophils. OBJECTIVES: We sought to determine the expression of IL-16 in epidermal cells in normal skin and skin from AD lesions and to investigate whether Langerhans cell (LC)-derived IL-16 may contribute to the initiation of atopic eczema. METHODS: The cutaneous expression of IL-16 was investigated by in situ hybridization and immunohistochemistry. Expression of IL-16 was also investigated in freshly isolated LCs and in keratinocytes by intracellular cytokine staining, quantitative real-time RT-PCR, and ELISA. RESULTS: Low levels of IL-16 mRNA, but no stored IL-16 protein, were detected in keratinocytes and LCs isolated from normal skin. Synthesis, storage, and secretion of IL-16 could be induced in LCs, but not keratinocytes, by activation with phorbol ester and ionomycin. In normal skin (n = 10) neither keratinocytes nor LCs expressed IL-16. In contrast, IL-16 was contained in approximately 40% of CD1a(+)LCs in patients with active AD (n = 16). IL-16 expression in LCs in patients with AD correlated with the number of infiltrating CD4(+)cells (r =.72, P =.0017) and was completely downregulated parallel to the clinical response of AD lesions to topical treatment with FK506. CONCLUSION: LC-derived IL-16 may participate in the recruitment and activation of inflammatory cells in AD.