L. Caradonna, M. L. Mastronardi, T. Magrone, R. Cozzolongo, R. Cuppone, O. G. Manghisi, D. Caccavo, N. M. Pellegrino, A. Amoroso, E. Jirillo and L. Amati Pages 995 - 1005 ( 11 )
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. Finally, novel therapeutic attempts aimed to neutralize LPS in the host are discussed.
endotoxemia lps,impaired phagocytic function,enteric bacterial antigen,novel therapeutic attempt,lactoferrin antibodies
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