Role of endotoxin in the hypermetabolic state after acute ethanol exposure

Am J Physiol. 1998 Dec;275(6):G1252-8. doi: 10.1152/ajpgi.1998.275.6.G1252.


This study investigated the role of endotoxin in the hypermetabolic state or swift increase in alcohol metabolism (SIAM) due to acute ethanol exposure. Female Sprague-Dawley rats (100-120 g) were given ethanol (5 g/kg) by gavage. Endotoxin measured in plasma from portal blood was not detectable in saline-treated controls; however, 90 min after ethanol, endotoxin was increased to 85 +/- 14 pg/ml, and endotoxin clearance was diminished by approximately 50%. Oxygen uptake in perfused livers was increased 48% by ethanol, and production of PGE2 by isolated Kupffer cells was increased similarly. These effects were blunted by elimination of gram-negative bacteria and endotoxin with antibiotics before ethanol administration. To reproduce ethanol-induced endotoxemia, endotoxin was infused via the mesenteric vein at a rate of 2 ng. kg-1. h-1. Endotoxin mimicked the effect of ethanol on oxygen uptake. The specific Kupffer cell toxicant GdCl3 completely prevented increases in oxygen uptake due to endotoxin. These findings demonstrate that endotoxin plays a pivotal role in SIAM, most likely by stimulating eicosanoid release from Kupffer cells.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Dinoprostone / biosynthesis
  • Endotoxins / blood
  • Endotoxins / metabolism
  • Endotoxins / pharmacology
  • Endotoxins / physiology*
  • Ethanol / pharmacology*
  • Female
  • Gadolinium / pharmacology
  • Kupffer Cells / metabolism
  • Liver / metabolism
  • Metabolism / drug effects*
  • Metabolism / physiology*
  • Oxygen Consumption / drug effects
  • Oxygen Consumption / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values


  • Anti-Bacterial Agents
  • Endotoxins
  • Ethanol
  • Gadolinium
  • Dinoprostone
  • gadolinium chloride