Acute alcohol intoxication and gadolinium chloride attenuate endotoxin-induced release of CC chemokines in the rat

Alcohol. 2000 Feb;20(2):193-203. doi: 10.1016/s0741-8329(99)00100-7.


This work tests the hypotheses that Kupffer cells are a major source of CC-chemokines (MIP-1alpha, MCP-1, RANTES) during acute endotoxemia and that acute ethanol intoxication modulates Escherichia coli lipopolysaccharide (LPS, 1 mg/Kg, i.v.)-induced chemokine release in the rat. LPS stimulated the release of CC-chemokines into the circulation, hepatic sequestration of leukocytes and liver injury. LPS-induced serum chemokines peaked at 1-3 h and could not be detected at 24-h posttreatment. Splenectomy significantly suppressed LPS-induced RANTES release, but not MIP-1alpha and MCP-1. Kupffer cell depletion by gadolinium chloride or acute ethanol intoxication significantly attenuated LPS-induced CC-chemokine release and hepatic injury. Hepatic sequestration of leukocytes during endotoxemia was also suppressed by acute ethanol. LPS downregulated the expression of MIP-1alpha and MCP-1 mRNAs and upregulated RANTES mRNA in Kupffer cells at 3-h post endotoxin. The expression of mRNAs was further suppressed in ethanol plus the LPS-treated group. Ethanol also suppressed the LPS-mediated priming of Kupffer cells for enhanced CC-chemokine release in vitro. Ethanol alone significantly upregulated the expression of CC-chemokine mRNA, and primed the Kupffer cells for enhanced RANTES release. CC-chemokine release and mRNA expression in hepatic sinusoidal endothelial cells were not significantly altered by ethanol, except for MCP-1 release. These data show that acute ethanol may be beneficial in tissue injury during acute endotoxemia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Alanine Transaminase / metabolism
  • Alcoholic Intoxication / metabolism*
  • Animals
  • Bacterial Toxins / antagonists & inhibitors
  • Bacterial Toxins / pharmacology
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / metabolism*
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / biosynthesis
  • Chemokine CCL5 / metabolism*
  • Endothelium / cytology
  • Endothelium / drug effects
  • Endothelium / metabolism
  • Endotoxins / antagonists & inhibitors*
  • Endotoxins / pharmacology
  • Enterotoxins / antagonists & inhibitors
  • Enterotoxins / pharmacology
  • Escherichia coli / metabolism
  • Escherichia coli Proteins*
  • Flow Cytometry
  • Gadolinium / pharmacology*
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Liver / cytology
  • Liver / metabolism
  • Macrophage Inflammatory Proteins / biosynthesis
  • Macrophage Inflammatory Proteins / metabolism*
  • Male
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Spleen / drug effects
  • Spleen / metabolism
  • Splenectomy


  • Bacterial Toxins
  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Endotoxins
  • Enterotoxins
  • Escherichia coli Proteins
  • Lipopolysaccharides
  • Macrophage Inflammatory Proteins
  • RNA, Messenger
  • Gadolinium
  • heat-labile enterotoxin, E coli
  • Alanine Transaminase