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.
Alcohol Clin Exp Res. 1996 Apr;20(2):293-301. doi: 10.1111/j.1530-0277.1996.tb01642.x.
Plasma clearance and organ distribution of intravenously injected human recombinant [125I]interleukin (IL)-6 and [125I]tumor necrosis factor (TNF)-alpha were studied in male rats, 2 hr after intravenous alcohol (ethanol) administration (single dose, 2.2 g.kg-1 body weight). Also, the rate of uptake and degradation of the two cytokines by the isolated, perfused rat liver was studied in the absence or in the presence of ethanol (35 mM) in the perfusate. Acute ethanol administration significantly increased plasma clearance rate for both cytokines (36% and 72%, for IL-6 and TNF-alpha, respectively), decreased the t1/2 alpha (30% and 11%, for IL-6 and TNF-alpha, respectively), abolished the slow (beta)-phase component for TNF-alpha, and increased t1/2 beta for IL-6 (31%). Although alcohol did not affect organ distribution of TNF-alpha, it increased the IL-6 content in the liver, kidney, and blood. IL-6 uptake rate by the isolated, perfused rat liver was 2-fold higher than TNF-alpha uptake, whereas the rate of degradation was larger for TNF-alpha than for IL-6, despite the fact that both cytokines were presented to the liver at the same concentration (6 nM). Ethanol addition to the perfusate (35 mM, final concentration) significantly increased TNF-alpha uptake (24%), without affecting IL-6 uptake or the degradation rate of either cytokine. Also, the kinetics of degradation by the isolated, perfused rat liver was linear for TNF-alpha, but exponential for IL-6. Data presented in this study demonstrate that: (1) acute alcohol consumption can alter the kinetic behavior of IL-6 and TNF-alpha in the bloodstream, mainly by accelerating their clearance which, in turn, may counteract the outcome of cytokine secretion and delivery to the blood; and (2) short exposure of liver to ethanol levels commonly seen in humans after binge drinking may alter its capacity to take up cytokines.
在雄性大鼠静脉注射乙醇（单剂量，2.2 g·kg⁻¹体重）2小时后，研究了静脉注射的人重组[¹²⁵I]白细胞介素（IL）-6和[¹²⁵I]肿瘤坏死因子（TNF）-α的血浆清除率和器官分布。此外，在灌注液中不存在或存在乙醇（35 mM）的情况下，研究了分离的灌注大鼠肝脏对这两种细胞因子的摄取和降解速率。急性给予乙醇显著增加了两种细胞因子的血浆清除率（IL-6和TNF-α分别增加36%和72%），降低了t1/2α（IL-6和TNF-α分别降低30%和11%），消除了TNF-α的慢（β）相成分，并增加了IL-6的t1/2β（31%）。虽然乙醇不影响TNF-α的器官分布，但它增加了肝脏、肾脏和血液中的IL-6含量。分离的灌注大鼠肝脏对IL-6的摄取率比TNF-α高2倍，而TNF-α的降解速率比IL-6大，尽管两种细胞因子以相同浓度（6 nM）呈现给肝脏。向灌注液中添加乙醇（最终浓度35 mM）显著增加了TNF-α的摄取（24%），而不影响IL-6的摄取或两种细胞因子的降解速率。此外，分离的灌注大鼠肝脏对TNF-α的降解动力学呈线性，而对IL-6呈指数关系。本研究中的数据表明：（1）急性饮酒可改变血液中IL-6和TNF-α的动力学行为，主要是通过加速它们的清除，这反过来可能抵消细胞因子分泌和输送到血液的结果；（2）肝脏短期暴露于人类暴饮后常见的乙醇水平可能会改变其摄取细胞因子的能力。
