Endotoxin stimulates hepatocyte interleukin-6 production

J Surg Res. 1999 Aug;85(2):251-8. doi: 10.1006/jsre.1999.5648.


Background: Interleukin-6 (IL-6) is a multifunctional cytokine which mediates many aspects of the acute phase response. Although known to be produced by macrophages and other proinflammatory cells, IL-6 is also released by many types of epithelial cells. The present studies were performed to determine if endotoxin and proinflammatory cytokines stimulate the release of IL-6 from native murine hepatocytes.

Methods: Cultured hepatocytes were treated with various concentrations of lipopolysaccharide (LPS), interleukin-1 (IL-1), or tumor necrosis factor (TNF), in the presence or absence of the IL-1 receptor antagonist (IL-1 RA), an anti-TNF antibody, or dexamethasone. Culture supernatants were assayed for murine IL-6 using an ELISA. The cellular source of IL-6 was investigated using immunohistochemical staining.

Results: Hepatocyte IL-6 production was significantly increased following treatment with LPS, IL-1, and TNF. Combinations of LPS and these cytokines were synergistic in stimulating IL-6 release. Dexamethasone, but not IL-1 RA or an anti-TNF antibody, inhibited hepatocyte production of IL-6 in response to LPS. Immunohistochemical staining revealed that the hepatocytes, and not contaminating nonparenchymal cells, were the principal source of the IL-6 produced in these cultures.

Conclusions: Murine hepatocytes release significant amounts of IL-6 when exposed to endotoxin or proinflammatory cytokines. LPS appears to stimulate hepatocyte IL-6 production directly, and this effect does not appear to be mediated by IL-1 or TNF.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / metabolism
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Immunohistochemistry
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / pharmacology
  • Interleukin-6 / biosynthesis*
  • Lipopolysaccharides / pharmacology*
  • Liver / drug effects*
  • Liver / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Sialoglycoproteins / pharmacology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / pharmacology


  • Antibodies
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • Receptors, Interleukin-1
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
  • Dexamethasone