Lin H Z, Yang S Q, Zeldin G, Diehl A M
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Alcohol Clin Exp Res. 1998 Aug;22(5 Suppl):231S-237S. doi: 10.1097/00000374-199805001-00004.
Increases in monocyte/macrophage production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), parallel the evolution of liver injury in rats and humans with alcoholic liver disease. However, the possibility that TNF-alpha expression may be induced in other cell populations before serious liver disease develops has not been evaluated. To clarify this issue, mRNAs and/or protein levels of TNF-alpha and cytokines [interleukin (IL)-6, IL-10, transforming growth factor-beta (TGF)-beta, IL-12, and interferon-gamma] that regulate its biological activity were measured in sera, liver, and adipose tissues of rats that had developed hepatic steatosis after consuming ethanol-containing diets for 6 weeks. Cytokine expression in the ethanol-fed groups was compared with that of pair-fed controls rats that had received isocaloric amounts of a similar, ethanol-free diet for the same time period. Animals were studied both before and after a surgical stress (partial hepatectomy) that is known to provoke cytokine production. Chronic ethanol consumption led to increased serum concentrations of TNF and related cytokines, at least in part, by inducing the overproduction of these factors in the liver and peripheral adipose tissues. Despite the pair-feeding protocol that ensured similar calorie consumption in both groups, adipose tissues in ethanol-fed rats also expressed more leptin, a TNF-alpha-inducible mRNA that encodes an appetite-suppressing hormone. Thus, white adipose tissue can be an important source of cytokines in nonobese animals and may be a target for ethanol's actions. These data implicate TNF-alpha as a potential mediator of the nutritional-metabolic aberrations that often accompany chronic alcohol intake, even in the absence of advanced liver disease.
在酒精性肝病的大鼠和人类中，促炎细胞因子肿瘤坏死因子-α（TNF-α）的单核细胞/巨噬细胞生成增加与肝损伤的进展平行。然而，在严重肝病发生之前，TNF-α表达是否可能在其他细胞群体中被诱导，这一可能性尚未得到评估。为了阐明这个问题，我们在食用含乙醇饮食6周后出现肝脂肪变性的大鼠的血清、肝脏和脂肪组织中，测量了TNF-α以及调节其生物活性的细胞因子[白细胞介素（IL）-6、IL-10、转化生长因子-β（TGF）-β、IL-12和干扰素-γ]的mRNA和/或蛋白质水平。将乙醇喂养组的细胞因子表达与同期接受等热量、类似无乙醇饮食的配对喂养对照大鼠的细胞因子表达进行比较。在已知会引发细胞因子产生的手术应激（部分肝切除术）前后对动物进行研究。长期摄入乙醇至少部分地通过诱导肝脏和外周脂肪组织中这些因子的过量产生，导致血清中TNF及相关细胞因子浓度升高。尽管采用了确保两组热量消耗相似的配对喂养方案，但乙醇喂养大鼠的脂肪组织也表达了更多的瘦素，瘦素是一种TNF-α诱导的mRNA，编码一种食欲抑制激素。因此，白色脂肪组织可能是非肥胖动物细胞因子的重要来源，并且可能是乙醇作用的靶点。这些数据表明，TNF-α是慢性酒精摄入常伴随的营养代谢异常的潜在介导因子，即使在没有晚期肝病的情况下也是如此。
