Sánchez Pérez M J, González-Reimers Emilio, Santolaria-Fernández Francisco, de la Vega-Prieto María José, Martínez-Riera Antonio, González Pedro Abreu, Rodríguez Rodríguez Eva, Durán-Castellón M Carmen
Servicio de Medicina, Interna' Hospital Universitario, Ofra s/n, Tenerife, Canary Islands, Spain.
Alcohol Alcohol. 2006 Nov-Dec;41(6):593-7. doi: 10.1093/alcalc/agl077. Epub 2006 Oct 7.
Increased exposure of Kupffer cells to intestinal-borne Gram-negative bacteria enhances the metabolism and leads to cytokine production by these cells. Activation of Kupffer cells increases free radical release, which may, in turn, enhance cytokine secretion, creating a positive feedback loop, which contributes to liver inflammation. Cytokines act on T cells, inducing their proliferation and secretion of additional interleukins. Lipid peroxidation products (malondialdehyde; MDA) form adducts with proteins and acetaldehyde, triggering a T cell immune response. Controversy exists about the predominance of either Th-1 or Th-2 cellular responses. We performed the present study in order to analyse the cytokine pattern in patients with acute alcoholic hepatitis, its relation to MDA and the relation between all these parameters and liver function and prognosis.
The study included 53 male alcoholics, 47 followed up for a median time of 32 months, during which 17 of them died. We measured serum MDA, tumour necrosis factor-alpha, interferon gamma (IFNG) and interleukins (IL) 4, 6, 8, and 10.
MDA levels were raised in cirrhotics and non-cirrhotics with alcoholic hepatitis, maintaining a relationship with bilirubin and Maddrey index, and with mortality in the univariate analysis. Both IFNG and IL-4 were raised in our patients compared with controls, as well as IL-8, and IL-6, but IL-10 were below the detection limit in the majority of cases, especially in cirrhotics. Using a Cox regression model, Maddrey index displaced MDA in the survival analysis.
Our data lend support to the hypothesis that activation of both Th-1 and Th-2 cell subsets take place. MDA levels are raised in alcoholics with alcoholic hepatitis and are closely related to liver function derangement and to survival, although this is displaced by Maddrey index using Cox regression model.
库普弗细胞与肠道来源的革兰氏阴性菌接触增加会增强其代谢并导致这些细胞产生细胞因子。库普弗细胞的激活会增加自由基释放，这反过来可能会增强细胞因子分泌，形成一个正反馈循环，从而导致肝脏炎症。细胞因子作用于T细胞，诱导其增殖并分泌更多白细胞介素。脂质过氧化产物（丙二醛；MDA）与蛋白质和乙醛形成加合物，引发T细胞免疫反应。关于Th-1或Th-2细胞反应何者占主导存在争议。我们开展本研究以分析急性酒精性肝炎患者的细胞因子模式、其与MDA的关系以及所有这些参数与肝功能和预后的关系。
该研究纳入了53名男性酗酒者，其中47人随访了中位时间32个月，在此期间有17人死亡。我们检测了血清MDA、肿瘤坏死因子-α、干扰素γ（IFNG）以及白细胞介素（IL）4、6、8和10。
酒精性肝炎的肝硬化患者和非肝硬化患者的MDA水平均升高，在单因素分析中与胆红素、马德雷指数以及死亡率相关。与对照组相比，我们的患者中IFNG和IL-4升高，IL-8和IL-6也升高，但在大多数情况下IL-10低于检测限，尤其是在肝硬化患者中。使用Cox回归模型，在生存分析中马德雷指数取代了MDA的地位。
我们的数据支持Th-1和Th-2细胞亚群均被激活这一假说。酒精性肝炎患者的MDA水平升高，且与肝功能紊乱和生存密切相关，尽管在使用Cox回归模型时这一关系被马德雷指数所取代。
