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

Department of Clinical Medicine, Immunology and Infectious Diseases, University of Bari, Bari, Italy, jirillo{at}midim.uniba.it, IRCCS 'Saverio de Bellis', Institute for Digestive Diseases, Castellana Grotte, Bari, Italy

D. Caccavo

Department of Clinical Medicine, Immunology and Infectious Diseases, University of Bari, Bari, Italy

T. Magrone

IRCCS 'Saverio de Bellis', Institute for Digestive Diseases, Castellana Grotte, Bari, Italy

E. Piccigallo

IRCCS 'Saverio de Bellis', Institute for Digestive Diseases, Castellana Grotte, Bari, Italy

L. Amati

IRCCS 'Saverio de Bellis', Institute for Digestive Diseases, Castellana Grotte, Bari, Italy

A. Lembo

Department of Clinical Medicine, Immunology and Infectious Diseases, University of Bari, Bari, Italy, Max Planck Institut für Immunbiologie, Freiburg, Germany

C. Kalis

Max Planck Institut für Immunbiologie, Freiburg, Germany

M. Gumenscheimer

Max Planck Institut für Immunbiologie, Freiburg, Germany

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)- induces hepatocyte apoptosis and lethal effects are due to secreted TNF- and not to cell-associated TNF-. An exaggerated production of TNF- has been reported in murine viral infections, in which mice become sensitized to low amounts of LPS and both interferon (IFN)- and IFN-/ß are involved in the macrophage-induced release of TNF-. The prominent role of LPS and TNF- 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-/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- and interleukin (IL)-1ß levels than responders. Moreover, in responders, an equilibrium between IFN- 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.

Journal of Endotoxin Research, Vol. 8, No. 5, 319-327 (2002)
DOI: 10.1177/09680519020080050501


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