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  The role of the liver in the response to LPS: experimental and clinical findings

Jirillo, E., Caccavo, D., Magrone, T., Piccigallo, E., Amati, L., Lembo, A., et al. (2002). The role of the liver in the response to LPS: experimental and clinical findings. Journal of Endotoxin Research, 8(5), 319-327.

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 Creators:
Jirillo, E., Author
Caccavo, D., Author
Magrone, T., Author
Piccigallo, E., Author
Amati, L., Author
Lembo, A.1, Author              
Kalis, C.1, Author              
Gumenscheimer, M.2, Author              
Affiliations:
1Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243649              
2Metchnikoff Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243654              

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 Abstract: The liver plays an important physiological role in lipopolysaccharide (LPS) detoxification and, in particular, hepatocytes are involved in the clearance of endotoxin of intestinal derivation. In experimental shock models, tumor necrosis factor (TNF)-α induces hepatocyte apoptosis and lethal effects are due to secreted TNF-α and not to cell- associated TNF-α. An exaggerated production of TNF-α has been reported in murine viral infections, in which mice become sensitized to low amounts of LPS and both interferon (IFN)-γ and IFN-α/β are involved in the macrophage-induced release of TNF-α. The prominent role of LPS and TNF-α in liver injury is also supported by studies of ethanol-induced hepatic damage. In humans, evidence of LPS-induced hepatic injury has been reported in cirrhosis, autoimmune hepatitis, and primary biliary cirrhosis and a decreased phagocytic activity of the reticulo-endothelial system has been found in these diseases. The origin of endotoxemia in hepatitis C virus (HCV) infected patients seems to be multifactorial and LPS may be of exogenous or endogenous derivation. In endotoxemic HCV-positive patients responsive to a combined treatment with IFN-α/ribavirin (RIB), endotoxemia was no longer detected at the end of the therapeutic regimen. By contrast, 48% of the non-responders to this treatment were still endotoxemic and their monocytes displayed higher intracellular TNF-α and interleukin (IL)-1β levels than responders. Moreover, in responders, an equilibrium between IFN-γ and IL-10 serum levels was attained. In the non-responders, serum levels of IL-10 did not increase following treatment. This may imply that an imbalance between T helper (Th)¹ and Th² derived cytokines could be envisaged in the non-responders.

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Language(s): eng - English
 Dates: 2002
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 20919
ISI: 000180150300003
 Degree: -

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Title: Journal of Endotoxin Research
  Alternative Title : J. Endoxtin Res.
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 8 (5) Sequence Number: - Start / End Page: 319 - 327 Identifier: ISSN: 0968-0519