Deaciuc I V, Alappat J M, McDonough K H, D'Souza N B
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
Biochem Pharmacol. 1996 Sep 27;52(6):891-9. doi: 10.1016/0006-2952(96)00416-9.
The effects of chronic (16-week) alcohol consumption by rats on [125I] tumor necrosis factor (TNF)-alpha and [125I]interleukin (IL)-6 plasma clearance and organ distribution in vivo and uptake and metabolism by the isolated, perfused liver were studied. Alcohol was administered to rats in a liquid diet for 16 weeks, and caused a decreased (48%) plasma clearance rate of IL-6 and converted the plasma clearance kinetics of the cytokine from a biphasic exponential in normal rats to a monophasic exponential decay. Alcohol feeding significantly increased (101%) plasma clearance of TNF-alpha, which followed a biphasic exponential decay and decreased the T1/2 for both the alpha (67%) and beta (76%) elimination components. The distribution of both cytokines in trichloroacetic acid precipitable and non-precipitable fractions of liver, spleen, stomach, small intestine (ileum), lung, kidney, and blood was also studied. The only effect of alcohol treatment was a significant decrease in IL-6 uptake and metabolism by the small intestine. Perfused livers, isolated from alcohol-fed rats, took up and metabolized larger amounts of IL-6 than did livers isolated from pair-fed rats. TNF-alpha uptake and metabolism by the isolated, perfused liver were not affected by chronic alcohol consumption. Regardless of the animal treatment, the isolated perfused liver took up and metabolized significantly larger (17-fold) amounts of TNF-alpha than IL-6, in spite of identical concentrations of cytokines (6 nM) in the perfusion medium. The data presented in this study along with our previous results demonstrating the effects of alcohol consumption on TNF-alpha and IL-6 receptors on various liver cells suggest that the effects of chronic alcohol treatment on cytokine clearance cannot be ascribed to changes in the receptors for the two cytokines. Also, no correlation was found between the effects of alcohol treatment on plasma cytokine clearance and uptake and metabolism of cytokines by the isolated, perfused liver. Experimental data and theoretical considerations suggest that cytokine receptor recycling may play an important role in mediating alcohol effects on cytokine clearance.
研究了大鼠长期（16周）摄入酒精对体内[125I]肿瘤坏死因子（TNF）-α和[125I]白细胞介素（IL）-6血浆清除率及器官分布，以及对离体灌注肝脏摄取和代谢的影响。以液体饲料形式给大鼠喂食酒精16周，结果导致IL-6血浆清除率降低（48%），并使该细胞因子的血浆清除动力学从正常大鼠的双相指数形式转变为单相指数衰减。喂食酒精显著增加了TNF-α的血浆清除率（101%），其遵循双相指数衰减，并降低了α（67%）和β（76%）消除成分的半衰期。还研究了两种细胞因子在肝脏、脾脏、胃、小肠（回肠）、肺、肾脏和血液的三氯乙酸可沉淀和不可沉淀部分中的分布。酒精处理的唯一影响是小肠对IL-6的摄取和代谢显著降低。从喂食酒精的大鼠分离的灌注肝脏比从配对喂食大鼠分离的肝脏摄取和代谢更多的IL-6。长期摄入酒精不影响离体灌注肝脏对TNF-α的摄取和代谢。无论动物的处理方式如何，尽管灌注培养基中细胞因子浓度相同（6 nM），离体灌注肝脏摄取和代谢的TNF-α量比IL-6显著多（17倍）。本研究中的数据以及我们之前关于酒精摄入对各种肝细胞上TNF-α和IL-6受体影响的结果表明，长期酒精处理对细胞因子清除的影响不能归因于这两种细胞因子受体的变化。此外，未发现酒精处理对血浆细胞因子清除率的影响与离体灌注肝脏对细胞因子的摄取和代谢之间存在相关性。实验数据和理论思考表明，细胞因子受体循环可能在介导酒精对细胞因子清除的影响中起重要作用。
