Prostaglandin E2 downregulates Kupffer cell production of IL-1 and IL-6 during hepatic regeneration

Am J Physiol. 1993 Apr;264(4 Pt 1):G601-8. doi: 10.1152/ajpgi.1993.264.4.G601.


The mammalian liver possesses the ability to regenerate to its original size after a 70% partial hepatectomy (PHx). The capacity of rat Kupffer cells (KC) isolated at specific intervals after PHx to produce interleukin (IL)-1, IL-6, and prostaglandin E2 (PGE2) in response to endotoxin [lipopolysaccharide (LPS)] stimulation was evaluated in standard RPMI 1640 (1,200 microM L-arginine) and arginine-depleted RPMI 1640 (< 10 microM L-arginine) media. Because KC function in an environment in which high arginase activity results in negligible L-arginine levels, the 10 microM L-arginine RPMI 1640 was used to simulate the hepatic microenvironment. Regenerating liver KC 12-120 h after PHx responded to LPS with a significantly greater (P < 0.05) production of IL-1 and IL-6 in standard RPMI 1640. This enhancement of regenerating liver KC to produce IL-1 and IL-6 was increased (P < 0.05) by placing these same KC in 10 microM arginine RPMI 1640 culture media. During the same time period, regenerating liver KC produced significantly elevated (P < 0.01) PGE2, again with greater differences in the low-arginine media. In vivo KC PGE2 blockade by indomethacin (5 mg/kg) significantly (P < 0.05) inhibited hepatic regeneration. When the cyclooxygenase inhibitor indomethacin (10 microM) was added to cultures, the production of PGE2 by KC was prevented, and in arginine-depleted cultures, IL-1 and IL-6 production was upregulated (P < 0.05). We conclude that during hepatic regeneration, KC IL-1 and IL-6 production is elevated and is controlled in an autoregulatory fashion by elevated KC PGE2 production.

Publication types

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

MeSH terms

  • Animals
  • Arginine / pharmacology
  • Cells, Cultured
  • Dinoprostone / biosynthesis
  • Dinoprostone / physiology*
  • Hepatectomy
  • Indomethacin / pharmacology
  • Interleukin-1 / biosynthesis*
  • Interleukin-6 / biosynthesis*
  • Kinetics
  • Kupffer Cells / drug effects
  • Kupffer Cells / immunology
  • Kupffer Cells / physiology*
  • Lipopolysaccharides / pharmacology
  • Liver Regeneration*
  • Macrophages / drug effects
  • Macrophages / physiology*
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / physiology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Salicylates / pharmacology
  • Salicylic Acid
  • Spleen / physiology


  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • Salicylates
  • Arginine
  • Dinoprostone
  • Salicylic Acid
  • Indomethacin