Biological and clinical significance of endotoxemia in the course of hepatitis C virus infection

L. Caradonna, M. L. Mastronardi, T. Magrone, R. Cozzolongo, R. Cuppone, O. G. Manghisi, D. Caccavo, N. M. Pellegrino, A. Amoroso, E. Jirillo, L. Amati

Research output: Contribution to journalArticle

Abstract

Endotoxins or lipopolysaccharides (LPS), major components of the cell wall of Gram-negative bacteria, once released from the bacterial outer membrane bind to specific receptors and, in particular, to a membrane-bound receptor, the CD14 (mCD14) and the toll-like receptor 4 present on monocytes/ macrophages. In turn, LPS-activated monocytes/ macrophages release in the host tissue an array of so-called proinflammatory cytokines and, among them, Tumor Necrosis Factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8 and IL-12 are the major mediators. Before therapy (To) and at the end of 6-month interferon (IFN)-α/Ribavirin (RIB) treatment (T6), circulating endotoxin levels were measured in responder and non responder HCV+ patients. At T0, 57% of the non responders were endotoxin-positive and had, on average, 54 pg/ml of plasma LPS while in 50% of the responder patients endotoxin were found with an average of 29 pg/ml. At T6, in responders LPS were no longer detectable, while in 42% of the non responders LPS were found (average levels 45 pg/ml). In terms of serum cytokine concentration, at T6 IFN-γ levels when compared to those detected at T0 were increased in both endotoxin-positive and endotoxin-negative patients. However, at T6 IL-10 concentration was significantly increased only in the group of endotoxin-negative subjects (responder patients), in comparison to T0 values. The origin of endotoxemia in HCV+ patients seems to be multifactorial, likely depending on impaired phagocytic functions and reduced T-cell mediated antibacterial activity. In these patients, however, one cannot exclude the passage of LPS from the gut flora to the blood stream, owing a condition of altered intestinal permeability. At the same time, a less efficient detoxification of enteric bacterial antigens at the hepatic level should be taken into consideration.

Original languageEnglish
Pages (from-to)995-1005
Number of pages11
JournalCurrent Pharmaceutical Design
Volume8
Issue number11
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Caradonna, L., Mastronardi, M. L., Magrone, T., Cozzolongo, R., Cuppone, R., Manghisi, O. G., Caccavo, D., Pellegrino, N. M., Amoroso, A., Jirillo, E., & Amati, L. (2002). Biological and clinical significance of endotoxemia in the course of hepatitis C virus infection. Current Pharmaceutical Design, 8(11), 995-1005.