Premium
Interleukin‐6 and Tumor Necrosis Factor‐α Clearance and Metabolism In Vivo and by the Isolated, Perfused Liver in the Rat: Effect of Acute Alcohol Administration
Author(s) -
Deaciuc Ion V.,
Alappat Julie M.,
McDonough Kathleen H.,
D'Souza Nympha B.
Publication year - 1996
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1996.tb01642.x
Subject(s) - tumor necrosis factor alpha , endocrinology , cytokine , in vivo , medicine , chemistry , ethanol , kidney , interleukin , metabolism , alcohol , necrosis , pharmacology , biology , biochemistry , microbiology and biotechnology
Plasma clearance and organ distribution of intravenously injected human recombinant [ 125 I]interleukin (IL)‐6 and [ 125 I]tumor necrosis factor (TNF)‐α 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‐α, respectively), decreased the t 1/2α (30% and 11%, for IL‐6 and TNF‐α, respectively), abolished the slow (β)‐phase component for TNF‐α, and increased t 1/2β for IL‐6 (31%). Although alcohol did not affect organ distribution of TNF‐α, 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‐α uptake, whereas the rate of degradation was larger for TNF‐α than for IL‐6, despite the fact that both cyokines were presented to the liver at the same concentration (6 nM). Ethanol addition to the perfusate (35 mM, final concentration) significantly increased TNF‐α 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‐α, 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‐α 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.