RESUMEN
A major cause of liver cirrhosis and hepatocarcinoma is chronic infection by hepatitis C virus. Ethanol consumption is the most significant environmental factor that exacerbates the progression of chronic hepatitis C to liver cirrhosis and hepatocarcinoma, perhaps due to increased cytokine secretion together with increased lipid peroxidation. In this study, we compare the intensity of lipid peroxidation (estimated as malondialdehyde (MDA) serum levels), the antioxidant status, (measured as glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities in red blood cells), and levels of cytokines derived from Th1 cells (such as interferon gamma (IFNG)), Th2 cells (such as interleukin (IL)-4), Th3 cells (such as transforming growth factor beta (TGF-beta)), and IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in patients affected by chronic hepatitis C virus infection, 26 drinkers of alcohol and 40 nondrinkers of alcohol. Patients showed significantly higher TNF-alpha (Z = 4.92, P < 0.001), IL-8 (Z = 4.95, P < 0.001), IFNG (Z = 2.81, P = 0.005), TGF-beta (t = 2.12, P = 0.037), MDA (Z = 5, P < 0.001), but lower IL-6 (Z = 3.61, P < 0.001) and GPX (F = 4.30, P < 0.05) than controls, whereas no differences were observed regarding IL-4 (Z = 0.35, P = 0.72), GPX and SOD activities. Alcoholics showed significantly higher TNF-alpha, but lower IL-4, MDA, and GPX, than nonalcoholics. TNF-alpha was significantly related to albumin and prothrombin activity, whereas TGF-beta was significantly related to MDA levels. Thus, cytokine secretion is altered in HCV infection. This alteration mainly consists of a stimulation of Th1 cytokines and an inhibition--or at least, no stimulation--of Th2 cytokines; these changes are especially marked among alcoholics with HCV infection, and are accompanied by raised TGF-beta.
Asunto(s)
Alcoholismo/sangre , Citocinas/sangre , Hepacivirus/fisiología , Hepatitis C Crónica/sangre , Peroxidación de Lípido/fisiología , Adulto , Alcoholismo/complicaciones , Estudios de Cohortes , Femenino , Hepatitis C Crónica/complicaciones , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Cytokines are mediators of the inflammatory response, secreted by many tissues, including adipocytes. Chronic alcoholic liver disease and alcoholic hepatitis are associated with elevated serum cytokine levels which yield prognostic value in this situation. Most studies have been performed in patients with acute alcoholic hepatitis. However, cytokine alterations in stable alcoholics have been less studied, as is also the case for the relationship between cytokines and fat and lean mass in these patients. The aim of the present study was to analyse the relationships between some proinflammatory serum cytokine levels and lean mass, fat mass, nutritional status, and liver function parameters in stable alcoholic patients. We determined serum TNF-alpha, interleukin (IL)-6, IL-8 and TNF receptor 2 (TNFr2) in 77 male alcoholic patients in a stable phase (before hospital discharge). In all patients we performed a total-body composition analysis (Hologic DEXA), nutritional assessment including body mass index, triceps skinfold, brachial perimeter, and assessment of liver function. Forty-two healthy volunteer health workers served as controls. IL-8, TNF-alpha and TNFr2 were significantly higher in patients than in controls. No differences were observed between patients and controls regarding fat mass, but alcoholics showed significantly decreased lean mass than controls. Only IL-6 was significantly related with body fat in patients with elevated IL-6 levels. Poor relationships were observed between lean mass and cytokines; some nutritional parameters showed inverse relationships with serum TNF, whereas TNF and IL-8 were inversely related with albumin and prothrombin activity. Thus, cytokine levels were elevated in stable alcoholic patients, and IL-6 levels showed significant correlation with body fat mass, raising the possibility that adipose tissue contributes to the persistence of high levels of cytokines in stable alcoholics.
Asunto(s)
Composición Corporal/inmunología , Citocinas/inmunología , Hepatopatías Alcohólicas/inmunología , Absorciometría de Fotón , Adulto , Anciano , Anciano de 80 o más Años , Citocinas/sangre , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estado Nutricional , Protrombina/metabolismo , Albúmina Sérica/metabolismo , Estadísticas no ParamétricasRESUMEN
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